Nanotechnology in Biomaterials: Revolutionizing Drug Delivery Systems

Ansheed Raheem
Centre for Biomaterials, Cellular and Molecular Theranostics (CBCMT), Vellore Institute of Technology, Vellore-632014, India
Correspondence to: ansheed@gmail.com

DOI: https://doi.org/10.70389/PJE.100001

Additional information

• Ethical approval: N/a
• Consent: N/a
• Funding: No industry funding
• Conflicts of interest: N/a
• Author contribution: Ansheed Raheem – Conceptualization, Writing – original draft, review and editing
• Guarantor: Ansheed Raheem
• Provenance and peer-review:
  Commissioned and externally peer-reviewed
• Data availability statement: N/a

Keywords: nanotechnology, biomaterials, drug delivery, nanoparticles, targeted therapy

Peer Review
Received: 24 August 2024
Revised: 9 September 2024
Accepted: 13 September 2024
Published: 11 October 2024

Introduction

According to the National Nanotechnology Initiative, USA, “nanotechnology” is the science of understanding and the manipulation of materials at an atomic or molecular scale.¹  Scanning tunneling microscopy and atomic force microscopy—sophisticated microscopy techniques—are two of the most important factors, among others, that have catalyzed the development of nanotechnology, enabling the engineering of materials at the nanoscale.² This has become a transformative force in biomedical science, particularly in the realm of drug delivery systems, opening numerous possibilities and advancements in the field. Traditional drug delivery systems frequently struggle with low bioavailability, non-specific targeting, and unpredictable drug release, which can result in diminished therapeutic effectiveness and heightened side effects. These conventional approaches often lack the precision needed to deliver drugs directly to the target site, inadvertently causing side effects and thereby causing damage to healthy tissues.³ Nanotechnology has revolutionized drug delivery by facilitating targeted delivery, controlled release, and improved drug stability.⁴ Nanoparticles can be precisely engineered to overcome biological barriers, deliver therapeutic agents directly to diseased cells, and release these agents in a controlled manner, thereby reducing side effects and optimizing treatment efficacy.⁵

Nanotechnology has transformed drug delivery systems by effectively addressing these longstanding challenges. One of the innovative approaches was by employing “nanoparticles” which are natural or engineered particles in the size range 1 nm to 100 nm.⁶ They are often designed from a variety of biomaterials that can encapsulate drugs, thereby significantly enhancing their solubility and protecting them from degradation.⁷ While drug encapsulation is a common strategy, other approaches, such as presenting drugs in nanoemulsions, quantum dots, mesoporous carriers, and nanocrystals, have also been developed to enhance drug delivery.^8–10 Several tissue-specific surface modifications are applied to nanoparticles, tailoring them for targeted delivery. These modifications enable the precise direction of drugs to diseased cells or tissues, thereby minimizing adverse effects on healthy areas.¹¹ Furthermore, nanotechnology facilitates the creation of smart drug delivery systems capable of releasing drugs in a controlled and sustained manner, often triggered by specific biological stimuli. These advancements not only enhance the efficacy and safety of treatments but also pave the way for personalized medicine, fundamentally revolutionizing the field of drug delivery.¹²

While there are multiple facets of application for nanotechnology in drug delivery, there is specific interest, particularly in cancer treatment, where nanoparticles are used to deliver chemotherapeutic agents directly to tumor cells, minimizing damage to healthy tissues. For instance, a study by Zhao et al. helped overcome doxorubicin (DOX) resistance in breast cancer by co-encapsulating DOX and resveratrol in a poly(lactic-co-glycolic acid) (PLGA)-based nanoparticle. This co-delivery system enhanced the accumulation of both drugs in the nucleus of resistant cancer cells, inhibited the expression of drug-resistance-related proteins (such as P-gp, MRP-1, and BCRP), and increased apoptosis by downregulating NF-κB and BCL-2. In tumor-bearing mice, this approach significantly inhibited tumor growth and reduced systemic toxicity compared to free DOX, highlighting its potential for treating resistant breast cancer.¹³

Furthermore, in gene therapy, nanotechnology has facilitated the development of non-viral vectors such as dendrimers and cationic liposomes, which efficiently deliver genetic material to specific cells, thereby reducing the risk of immune responses, insertional mutagenesis, toxicity, and off-target gene expression. These nanocarriers not only protect the genetic material from degradation but also enhance its entry into target cells, ultimately improving therapeutic outcomes.¹⁴ A study by Ren et al. demonstrated the potential of this approach by developing a dendrimer carrier for the co-delivery of anticancer drugs and miRNA to human brain glioma cell lines. Specifically, a system combining PAMAM dendrimers with antisense-miR-21 oligonucleotide and 5-fluorouracil was utilized. The results indicated that this combination significantly improved the cytotoxicity of the drug, increased apoptosis in U251 cells (a human brain glioma cell line), and reduced the migration ability of tumor cells. This study underscores the effectiveness of dendrimers as delivery vectors in targeted cancer therapy.¹⁵

With nanotechnology expanding its outreach into various aspects of medical science, this paper will comprehensively examine the current landscape of nanotechnology in biomaterials, focusing on its transformative impact on drug delivery systems. It will cover the various types of nanomaterials used, the mechanisms of drug delivery, and the latest applications in disease treatment. Additionally, the paper will discuss the challenges and limitations faced by this emerging field, as well as future outlooks and innovations. The objective is to provide a holistic understanding of how nanotechnology is revolutionizing drug delivery, with an emphasis on the latest advancements and interdisciplinary collaborations shaping the future of healthcare.

Types of Nanomaterials Used in Drug Delivery

There are numerous nanomaterials, both synthetic and natural, with tunable properties that are specifically suited for drug delivery applications. When engineering a nanomaterial for drug delivery, several critical aspects must be considered. These nanoparticles should be biodegradable within the human body, ensuring that once they have fulfilled their intended function, they can be broken down into non-toxic byproducts. This prevents their accumulation in the body and minimizes long-term side effects. Additionally, the nanomaterials must be biocompatible, meaning they should not provoke adverse immune responses or toxicity.¹⁶ Other factors influencing the selection of nanoparticles are detailed in Table 1 below.

Table 1: Factors determining the choice of nanoparticles for drug delivery application.

Factor	Description	Importance	Ref
Biocompatibility	The material should not induce adverse immune responses or toxicity.	Ensures safety and prevents harmful reactions in the body.	16
Biodegradability	Ability to be broken down into non-toxic byproducts.	Prevents accumulation in the body and reduces long-term side effects.	16
Size	Optimal size is typically between 10and 100 nm for effective delivery.	Affects tissue penetration, cellular uptake, and clearance.	17
Surface properties	Surface charge and wettability impact interaction with cells and proteins.	Influences cellular uptake, circulation time, and potential toxicity.	18
Drug loading	Ability to carry a high	Determines the dosage and	19

Factor	Description	Importance	Ref
Capacity	amount of therapeutic agent.	efficacy of the drug delivery system.
Release kinetics	Controlled release of the drug at a desired rate.	Ensures sustained therapeutic levels and reduces dosing frequency.	20
Active targeting	Surface functionalization with ligands or antibodies for specific cell targeting.	Enhances precision of drug delivery to diseased tissues, minimizing side effects.	21
Passive targeting	Utilization of the enhanced permeability and retention (EPR) effect in tumors.	Allows for natural accumulation in target tissues, particularly in cancer therapy.	22
Stability	Stability in formulation and after administration, avoiding premature release or degradation.	Ensures the nanomaterial remains effective throughout its use and storage.	23
Shelf life	Longevity of the nanomaterial during storage.	Essential for practical use and commercial viability.	23
Immunogenicity	Potential to trigger immune responses should be minimized.	Reduces the risk of inflammation, hypersensitivity, or other immune reactions.	23
Manufacturing	Scalable, reproducible, and cost-effective production processes.	Necessary for commercial production and regulatory compliance.	24

Factor	Description	Importance	Ref
Scalability	Ability to produce nanomaterials at a large scale while maintaining quality.	Critical for widespread clinical and commercial use.	24
Regulatory approval	Compliance with regulatory standards for safety, efficacy, and quality.	Required for clinical use and commercialization of nanomaterials.	25
Ethical considerations	Ethical implications, including patient consent and long-term effects.	Ensures responsible development and use, particularly in sensitive applications like gene therapy.	25

Lipid-Based Nanomaterials

Lipid-based nanomaterials have become a significant advancement in the field of drug delivery, providing notable advantages in the encapsulation and delivery of therapeutic agents. Among these, liposomal is a prominent example.²⁶ Liposomal nanoparticles represent a significant advancement in drug delivery, offering numerous benefits due to their unique structure and biocompatibility. These vesicles, typically composed of lipid bilayers, can encapsulate lipophilic, hydrophilic, and hydrophobic drugs, thus enhancing the therapeutic efficacy while reducing toxicity.^27,28 The flexibility in their design allows for controlled release, targeted delivery, and protection of the encapsulated drug from degradation, which is critical for treating diseases like cancer and infections.²⁹

The liposomal formulation ensures that drugs are delivered precisely to the target site, minimizing systemic side effects and improving the pharmacokinetic profiles of drugs. For example, Doxil®, a liposomal formulation of DOX, has demonstrated reduced cardiotoxicity compared to its free drug counterpart.³⁰ There are several studies highlighting the efficacy of liposomal intervention in drug delivery. For instance, Una et al. explored the use of a novel liposomal delivery system for dexamethasone phosphate (DXM-P) to treat collagen-induced arthritis in rodents, aiming to separate the therapeutic benefits of glucocorticoids from their typical side effects.

The liposomal DXM-P provided a prolonged anti-inflammatory effect with fewer side effects compared to the free form of the drug. Notably, a single dose of the liposomal formulation was as effective as multiple daily doses of the free drug but resulted in less suppression of the hypothalamus-pituitary-adrenal (HPA) axis, lower impact on blood glucose levels, and milder hematological changes. Specifically, a single dose of liposomal DXM-P, especially at 4 mg/kg, was sufficient to reduce joint swelling for up to 7 days, whereas the free form required daily dosing to achieve a similar effect, as shown in Figure 2. Also, liposomal DXM-P was more successful in decreasing collagen breakdown, as indicated by lower pyridinoline levels in urine, suggesting better protection against joint tissue degradation, as highlighted in Figure 2. The liposomal DXM-P offers significant advantages over free DXM-P, including a sustained anti-inflammatory effect with fewer doses, reducing the need for daily administration. It minimizes typical glucocorticoid side effects, such as suppression of the HPA axis and hyperglycemia, which are more pronounced with free DXM-P. The liposomal form also allows for better targeting, accumulating mainly in the spleen and avoiding excessive liver exposure, resulting in higher therapeutic efficacy with lower drug amounts and fewer side effects. This suggests that liposomal DXM-P could offer a more targeted and safer approach to treating inflammatory diseases like arthritis. ³¹

Lipid-based drug delivery systems have evolved significantly, extending beyond the traditional liposome-based models to encompass a range of innovative approaches, each offering distinct advantages for therapeutic applications. Solid lipid nanoparticles and nanostructured lipid carriers are particularly noteworthy for their ability to provide controlled drug release and enhanced stability, especially in the context of poorly water-soluble drugs.³² The use of micelles, composed of amphiphilic molecules, has proven effective in increasing the solubility and bioavailability of hydrophobic drugs.³³ Transfersomes, recognized for their ultra-deformability, have emerged as a promising option for transdermal drug delivery, enhancing the penetration of therapeutic agents through the skin.³⁴ Additionally, niosomes, which are structurally similar to liposomes but formulated from non-ionic surfactants, offer enhanced stability and versatility, making them suitable for delivering a wide array of drugs.³⁵ Collectively, these diverse lipid-based delivery systems are instrumental in advancing drug delivery technologies, contributing to improvements in drug solubility, stability, and targeted therapeutic efficacy.

Polymer-Based Nanomaterials

Polymeric nanoparticles (PNPs), which are submicron-sized colloidal particles typically ranging from 10 to 1,000 nm, have emerged as a promising platform in the realm of drug delivery systems. ³⁶ These nanoparticles are made from polymers that are both biodegradable and biocompatible, incorporating natural substances like chitosan and alginate, along with synthetic polymers such as PLGA and polycaprolactone.³⁷ The primary design of PNPs is to encapsulate therapeutic agents, offering protection from degradation while simultaneously enhancing their stability, bioavailability, and targeted delivery. One of the defining features of PNPs is their capacity to encapsulate a broad spectrum of therapeutic agents, including small molecules, proteins, peptides, and nucleic acids, thus enabling controlled and sustained drug release.⁵ This encapsulation strategy not only safeguards drugs from premature degradation within the biological milieu but also prolongs their circulation time within the bloodstream. Furthermore, PNPs can be engineered to respond to specific stimuli—such as pH fluctuations, temperature changes, or enzymatic activity—commonly found in pathological environments like tumors or inflamed tissues. This stimulus-responsive release ensures that the therapeutic agents are delivered precisely where they are needed, maximizing efficacy while minimizing off-target effects.³⁸

A significant advantage of PNPs lies in their ability to target specific tissues or cells, which substantially reduces the systemic side effects often associated with conventional drug delivery methods. By functionalizing the surface of PNPs with biomolecules, antibodies, or specific ligands that can recognize and bind to target cell receptors, drugs can be selectively delivered to diseased cells while sparing healthy tissues.²¹ This targeted approach is particularly beneficial in cancer therapy, where PNPs can direct chemotherapeutic agents specifically to tumor cells, thereby reducing the collateral damage to normal tissues and minimizing adverse effects. Compared to traditional drug delivery systems, PNPs offer several notable benefits. They significantly improve the bioavailability of drugs, particularly hydrophobic molecules that are otherwise plagued by poor solubility and absorption.³⁹

The polymer matrix of PNPs allows for controlled and sustained drug release, thereby reducing the frequency of dosing and improving patient compliance.³⁹ Additionally, the encapsulation of drugs within PNPs shields them from harsh biological environments, such as the acidic conditions of the gastrointestinal tract or enzymatic degradation in the bloodstream—this is particularly crucial for the delivery of sensitive biomolecules like proteins and nucleic acids.⁴⁰ Moreover, PNPs take advantage of the enhanced permeability and retention (EPR) effect observed in tumor tissues. The leaky vasculature and impaired lymphatic drainage characteristic of tumors allow nanoparticles to preferentially accumulate at the tumor site, thereby improving drug delivery and enhancing therapeutic efficacy while reducing systemic toxicity. This targeted accumulation, coupled with controlled drug release, minimizes the exposure of non-target tissues to therapeutic agents, leading to a better safety profile and fewer side effects.⁴¹

In their 2014 study, Snipstad et al. investigated the efficacy of PNPs in enhancing the intracellular delivery of hydrophobic drugs, using Nile red as a model compound. The researchers encapsulated Nile red within poly(butyl cyanoacrylate) (PBCA) nanoparticles and observed a significant increase in drug uptake by cells compared to the free drug. This enhancement in drug uptake was quantitatively confirmed using flow cytometry, as illustrated in Figure 3 (a) and (b)where encapsulated Nile red exhibited markedly improved cellular uptake. Furthermore, confocal laser scanning microscopy provided visual confirmation of this increased uptake. The microscopy images in Figure 3 (f), (g), and (h) clearly demonstrated that Nile red, when encapsulated within the PBCA nanoparticles, was taken up by cells more effectively when compared to the free drug in Figure 3 (c), (d), and (e). This

enhanced uptake was attributed to a mechanism of contact-mediated transfer, where the nanoparticles directly delivered the drug into the cytosol, effectively bypassing the traditional endocytosis pathway and avoiding lysosomal degradation. This study underscores the potential of PNPs in delivering a hydrophobic drug, particularly in challenging therapeutic areas such as cancer treatment. By enhancing intracellular delivery and avoiding degradation pathways, PBCA nanoparticles can improve the efficacy of hydrophobic drugs, providing a promising strategy for the development of more effective cancer therapies.⁴²

Inorganic Nanomaterials

Inorganic nanoparticles are engineered from materials such as metals and oxides that can be tailored to enhance the delivery of drugs, particularly in challenging contexts like cancer treatment and chronic diseases.⁴³ Inorganic nanoparticles such as gold nanoparticles (AuNPs), silver nanoparticles (AgNPs), and magnetic nanoparticles (MNPs) are gaining prominence due to their unique properties.^44,45 Gold nanoparticles, for example, are known for their excellent biocompatibility and ease of surface modification, which allows for targeted drug delivery and imaging. Silver nanoparticles, while widely recognized for their antimicrobial properties, also show promise in cancer treatment, where they can induce cytotoxic effects through mechanisms such as reactive oxygen species generation. MNPs, typically composed of iron oxide (Fe₃O₄), offer the dual advantage of drug delivery and hyperthermia treatment, where they are channeled to the site of tumor growth with magnetism and then heated to kill cancer cells.^44,45

One of the primary advantages of using inorganic nanoparticles in drug delivery is their biodegradability, particularly when combined with polymers like PLGA. Biodegradable nanoparticles gradually break down within the body, releasing the drug that is encapsulated in a controlled manner, which is crucial for maintaining therapeutic levels of the drug over extended periods. This sustained release reduces the frequency of drug administration and minimizes side effects, making treatment more manageable for patients.⁴⁶ Another significant benefit of the ability of inorganic nanoparticles is specificity, where the nanoparticle can target specific tissues and cells. This targeting capability can be achieved through surface modifications, such as PEGylation, or by attaching targeting ligands that recognize specific receptors on the surface of cancer cells. For instance, gold nanoparticles can be conjugated with antibodies or peptides that specifically bind to tumor markers, ensuring that the therapeutic agent is delivered directly to the cancer cells, sparing healthy tissues from the cytotoxic effects.⁴⁷ Moreover, the small size and high surface-area-to-volume ratio of these nanoparticles allow for efficient drug loading and delivery. The EPR effect is a phenomenon utilized in cancer therapy where nanoparticles can passively accumulate in tumors. This effect occurs because the leaky vasculature of tumors allows nanoparticles to penetrate and remain within the tumor tissue, facilitating targeted drug delivery. This property is particularly beneficial in delivering chemotherapeutic drugs, which are often limited by their non-specific distribution in the body.⁴¹

In a study by Rahul et al., the efficacy of doxorubicin-loaded hollow gold nanospheres (Dox@HAuNS) for treating liver cancer was explored through a combination of photothermal ablation (PTA) and chemoembolization. Utilizing a rabbit model of liver cancer, the researchers demonstrated the potential of this dual therapeutic approach. The Dox@HAuNS nanoparticles were delivered directly into the tumor via trans-arterial injection, followed by near-infrared laser irradiation. Rabbits that received the PTA in combination with the nanoparticle formulation exhibited significant tumor reduction, as shown in Figure 4a. By the 14th day, all three variations of the nanoparticle treatment had significantly reduced tumor volume, with the most pronounced initial effect observed in the Dox@HAuNS + PTA group, as depicted in Figure 4 (b) and c. This approach facilitated targeted drug delivery and localized heating, leading to substantial tumor reduction. The study underscores the potential of gold nanoparticles to enhance cancer treatment by integrating chemotherapy with thermal ablation.⁴⁸

Apart from the above-mentioned nanomaterial-mediated drug delivery systems, stimuli-responsive, carbon-based, biological, and hybrid nanomaterials are other choices for delivery systems. Stimuli-responsive nanomaterials are engineered to react to specific environmental triggers like pH, temperature, or light, enabling controlled drug release precisely at the target site. This targeted approach reduces side effects and increases treatment efficacy, particularly in cancer therapies.⁴⁹ Carbon-based nanomaterials, like carbon nanotubes and graphene, excel in drug delivery due to their high surface area and ability to be functionalized, improving solubility, biocompatibility, and targeted delivery. These materials are especially promising for delivering chemotherapeutics and genetic materials while minimizing harm to healthy cells.⁵⁰ Biological nanomaterials leverage the inherent biocompatibility of natural molecules, facilitating immune system evasion and improving the effectiveness of vaccines and gene therapies.⁵¹ Hybrid nanomaterials combine the advantages of different nanomaterials, enhancing drug delivery through synergistic effects, making treatments more efficient, and reducing potential side effects. ⁵²

Mechanisms of Drug Delivery Using Nanotechnology

Nanoparticle-mediated drug delivery systems have several advantages over others due to the various mechanisms they adopt to deliver drugs. Some of the peculiar physicochemical properties of nanoparticles, such as their small size, large surface area, and modifiable surface characteristics, enable them to utilize various mechanisms to transport therapeutic agents to specific sites within the body.⁵³ Figure 5 highlights various mechanisms employed by nanoparticles to deliver drugs effectively. Further below are the different mechanisms employed by nanoparticles in drug delivery, focusing on how these mechanisms enhance therapeutic efficacy and reduce adverse effects.

Passive Targeting

The EPR phenomenon is a pivotal mechanism in nanoparticle-mediated drug delivery, particularly in the treatment of cancer, which is a major mechanism used for the passive targeting of drugs. Matsumura et al. were the first to report the EPR effect, demonstrating how it enables nanoparticles to accumulate in tumors. This accumulation occurs due to the leaky vasculature and poor lymphatic drainage characteristic of tumors, which is typically more permeable than that of normal tissues due to its rapid and abnormal angiogenesis.⁵⁴ The EPR effect allows nanoparticles to accumulate selectively in tumor tissues, enhancing drug concentration at the target site while minimizing systemic exposure. Nanoparticles, due to their small size and modifiable surface properties, can navigate through the leaky blood vessels of tumors and evade rapid clearance by the lymphatic system.

This passive targeting mechanism is particularly advantageous for delivering chemotherapeutic agents, as it increases the therapeutic index and reduces the side effects associated with conventional chemotherapy. The EPR effect has been widely studied and forms the basis for many nanoparticle-based drug delivery systems currently under development, offering a promising approach for improving the efficacy of cancer treatments while minimizing damage to healthy tissues.^55,56 One of the profound applications was the drug Doxil, a liposomal formulation of DOX, which is designed to exploit the EPR effect to accumulate preferentially in tumor tissues. This formulation has been shown to significantly enhance the delivery of DOX to tumors, improving therapeutic outcomes while reducing side effects compared to the free drug.²²

Active Targeting

Active targeting via ligand-directed nanoparticles represents a significant advancement in precision medicine, enabling the delivery of therapeutic drugs or agents directly into those cells that are diseased. This approach leverages the specificity of ligands, such as antibodies, peptides, or small molecules, which are conjugated to the surface of nanoparticles. These ligands are designed to bind selectively to receptors that are overexpressed on target cells, such as cancer cells or cells within inflamed tissues. Upon binding, the ligand-nanoparticle complex can be internalized through receptor-mediated endocytosis, allowing for the localized release of the drug within the target cell. This method enhances the efficacy of treatment by concentrating the drug at the site of disease, reducing the required dosage, and minimizing systemic toxicity.

The precision and effectiveness of ligand-directed nanoparticles make them a promising tool for targeted drug delivery application, offering hope for more effective treatments with fewer side effects.^17,56 For instance, a study by Elena et al. explores the development of terpolymer-based nanocapsules functionalized with folic acid to selectively target cancer cells that overexpress folate receptors. These nanocapsules are engineered to deliver DNA specifically to cancer cells, offering a more targeted and controlled release mechanism. By focusing on direct delivery to cancer cells, this approach seeks to enhance the efficacy of cancer therapy, minimizing the impact on healthy cells and reducing the side effects typically associated with conventional treatments [57].

Stimuli-Responsive Drug Delivery

Stimuli-responsive drug release mechanisms in nanoparticle-mediated drug delivery represent a sophisticated approach to achieving precise and controlled therapeutic outcomes. These mechanisms leverage the unique environmental conditions of diseased tissues, such as pH, temperature, and enzymatic activity, to trigger the release of drugs from nanoparticles at the target site.³⁸ This ensures that the drug is released specifically where it is needed, minimizing off-target effects. For instance, pH-responsive nanoparticles are designed to release their cargo in acidic environments, such as those found in tumor tissues or intracellular compartments like endosomes and lysosomes.⁵⁸ Temperature-responsive nanoparticles, on the other hand, release drugs in response to elevated temperatures, a common feature of inflamed or cancerous tissues.⁵⁹ Similarly, enzyme-responsive nanoparticles release their therapeutic load when exposed to specific enzymes that are overexpressed in diseased tissues.³⁸ These stimuli-responsive systems not only enhance the therapeutic efficacy of the drug but also allow for a reduction in the overall dosage required, thereby decreasing potential side effects. The development and refinement of these mechanisms continue to be a focal point in the advancement of targeted and personalized medicine, offering promising prospects for the treatment of complex diseases.³⁸

Mucoadhesion

Mucoadhesion-based nanoparticle drug delivery systems allow for prolonged retention at mucosal sites and enhance drug absorption. This characteristic is particularly advantageous for drugs targeting mucosal tissues such as the gastrointestinal tract, nasal cavity, and eyes.⁶⁰ Chitosan, a biopolymeric material, is commonly used in these systems due to its superior mucoadhesive properties. It enhances adhesion to the mucus layer through electrostatic interactions with the negatively charged mucin, resulting in increased residence time and sustained drug release. Nanoparticles with mucoadhesive properties, such as those formulated with chitosan or its derivatives, can be administered via various routes, including oral, nasal, ocular, and pulmonary pathways. These nanoparticles interact effectively with mucosal tissues, improving drug bioavailability by shielding the drug from enzymatic degradation and facilitating closer contact with the absorption site.⁶¹

Additionally, the sustained release enabled by mucoadhesion helps maintain therapeutic drug levels over extended periods, thereby reducing dosing frequency and enhancing patient compliance. Particle size and surface charge are two critical factors that influence the effectiveness of mucoadhesive nanoparticles in drug delivery. These factors play a significant role in determining the interaction between nanoparticles and mucosal tissues, impacting drug absorption and retention.⁶² Due to these properties, mucoadhesive nanoparticles offer a versatile platform for targeted and controlled drug delivery applications. One of the best examples is a study demonstrated by Jan et al., in which the team developed a mucoadhesive nanoparticulate drug delivery system using thiolated chitosan nanoparticles for targeted drug release in the urinary bladder. The system enhances drug adhesion to the bladder mucosa and provides sustained release, potentially improving the effectiveness of intravesical therapies for bladder diseases like interstitial cystitis.⁶³

Challenges and Limitations

Nanoparticle-mediated drug delivery holds significant promise in improving the efficacy and specificity of therapeutic interventions, particularly in fields like oncology. However, several caveats hinder the widespread application of this technology in current therapeutics.

One major challenge is the complexity of biological environments, which can significantly affect the stability, distribution, and release profile of nanoparticles. Once administered, nanoparticles encounter various biological barriers, such as the immune system’s rapid clearance mechanisms, which can reduce their effectiveness. This is especially problematic when delivering drugs to specific sites in the body, such as tumors, where precise targeting is critical. Overcoming these barriers often requires intricate design and functionalization of nanoparticles, which add complexity and cost to their development.⁶⁴ Toxicity is another significant concern. While nanoparticles can enhance drug delivery, their small size and unique properties can also lead to unintended interactions with cells and tissues, potentially causing adverse effects. Nanoparticle accumulation in the body over a longer period of time might cause some effects that have not been fully explored. Efforts to mitigate toxicity include the use of biodegradable materials and natural compounds in nanoparticle formulations, but more research is needed to ensure these solutions are effective. ^25,65

Moreover, the manufacturing and scalability of nanoparticle-based drug delivery systems pose additional challenges. The precise engineering required for these systems, combined with the need for rigorous quality control, can make large-scale production difficult and expensive. This limits the accessibility of these advanced therapies, particularly in resource-constrained settings.²⁴ Regulatory hurdles remain a significant barrier. The novel nature of nanoparticle-mediated drug delivery requires new regulatory frameworks to ensure safety and efficacy, which can delay the approval and adoption of these technologies.^64,65 Addressing these challenges will be critical for advancing nanoparticle-mediated drug delivery systems and realizing their potential in personalized medicine and beyond.

Future Outlook and Conclusion

The future of nanoparticle-mediated drug delivery is highly promising, marked by advancements that could revolutionize personalized medicine. Nanoparticles are expected to become central in tailoring treatments to individual patients, particularly in targeting specific sites within the body, thus enhancing therapeutic efficacy while minimizing side effects. Ongoing innovations in nanotechnology will likely improve the functionality and safety of these systems, making them more efficient and reducing toxicity. Another highlight is the use of nanoparticles in combination therapies, which could be a game changer in cancer therapy. As regulatory frameworks and manufacturing processes evolve, these therapies are expected to become more accessible and applicable beyond oncology, potentially addressing a wide range of diseases, including neurological and cardiovascular disorders.^66–68

In conclusion, nanotechnology has significantly transformed drug delivery systems, offering unprecedented precision in targeting, controlled release, and reduced side effects. Through the use of various nanomaterials like lipid-based, polymeric, and inorganic nanoparticles, these systems can enhance the bioavailability and stability of therapeutic agents while minimizing their adverse effects. These advancements not only pave the way for more effective treatments but also enable personalized medicine, particularly in challenging fields such as oncology. Several studies have demonstrated that conventional therapeutics can be effectively supplemented or even completely replaced with the introduction of nanoparticles. As regulatory frameworks evolve, nanoparticle-mediated drug delivery is poised to become a cornerstone of future therapeutic strategies, with broad applications across various medical fields. This revolution in drug delivery highlights the profound potential of nanotechnology in advancing global healthcare.

References

1 About Nanotechnology | National Nanotechnology Initiative n.d. Accessed August 17, 2024. https://www.nano.gov/about-nanotechnology.
 
2 Mody CCM. Instrumental Community: Probe Microscopy and the Path to Nanotechnology. Instrumental Community 2011. https://doi.org/10.7551/MITPRESS/9780262134941.001.0001.
https://doi.org/10.7551/mitpress/9780262134941.001.0001
 
3 Utreja P, Jain SK, Tiwary A. Novel drug delivery systems for sustained and targeted delivery of anticancer drugs: Current status and future prospects. Curr Drug Deliv. 2010;7:152-61. https://doi.org/10.2174/156720110791011783.
https://doi.org/10.2174/156720110791011783
 
4 Simonazzi A, Cid AG, Villegas M, Romero AI, Palma SD, Bermúdez JM. Nanotechnology applications in drug controlled release. Drug Targeting and Stimuli Sensitive Drug Delivery Systems 2018:81-116. https://doi.org/10.1016/B978-0-12-813689-8.00003-3.
https://doi.org/10.1016/B978-0-12-813689-8.00003-3
 
5 Yetisgin AA, Cetinel S, Zuvin M, Kosar A, Kutlu O. Therapeutic nanoparticles and their targeted delivery applications. Molecules. 2020;25:2193. https://doi.org/10.3390/MOLECULES25092193.
https://doi.org/10.3390/molecules25092193
 
6 Murthy SK. Nanoparticles in modern medicine: State of the art and future challenges. Int J Nanomed. 2007;2:129.
 
7 Trucillo P. Biomaterials for drug delivery and human applications. Materials. 2024;17:456. https://doi.org/10.3390/MA17020456.
https://doi.org/10.3390/ma17020456
 
8 Li X, Tsibouklis J, Weng T, Zhang B, Yin G, Feng G, et al. Nano carriers for drug transport across the blood-brain barrier. J Drug Target. 2017;25:17-28. https://doi.org/10.1080/1061186X.2016.1184272.
https://doi.org/10.1080/1061186X.2016.1184272
 
9 -Uwe J, Junghanns AH, Müller RH. Nanocrystal technology, drug delivery and clinical applications. Int J Nanomed. 2008;3:295. https://doi.org/10.2147/IJN.S595.
https://doi.org/10.2147/IJN.S595
 
10 Qi L, Gao X. Emerging application of quantum dots for drug delivery and therapy. Expert Opin Drug Deliv. 2008;5:263-7. https://doi.org/10.1517/17425247.5.3.263.
https://doi.org/10.1517/17425247.5.3.263
 
11 Patel P, Hanini A, Shah A, Patel D, Patel S, Bhatt P, et al. Surface modification of nanoparticles for targeted drug delivery. Surface Modification of Nanoparticles for Targeted Drug Delivery 2019:19-31. https://doi.org/10.1007/978-3-030-06115-9_2.
https://doi.org/10.1007/978-3-030-06115-9_2
 
12 Jia L, Zhang P, Sun H, Dai Y, Liang S, Bai X, et al. Optimization of nanoparticles for smart drug delivery: A review. Nanomaterials. 2021;11:2790. https://doi.org/10.3390/NANO11112790.
https://doi.org/10.3390/nano11112790
 
13 Zhao Y, Huan ML, Liu M, Cheng Y, Sun Y, Cui H, et al. Doxorubicin and resveratrol co-delivery nanoparticle to overcome doxorubicin resistance. Sci Rep. 2016;6:1-15. https://doi.org/10.1038/srep35267.
https://doi.org/10.1038/srep35267
 
14 Wakaskar RR. General overview of lipid-polymer hybrid nanoparticles, dendrimers, micelles, liposomes, spongosomes and cubosomes. J Drug Target. 2018;26:311-8. https://doi.org/10.1080/1061186X.2017.1367006.
https://doi.org/10.1080/1061186X.2017.1367006
 
15 Chis AA, Dobrea CM, Rus LL, Frum A, Morgovan C, Butuca A, et al. Dendrimers as non-viral vectors in gene-directed enzyme prodrug therapy. Molecules 2021;26. https://doi.org/10.3390/MOLECULES26195976.
https://doi.org/10.3390/molecules26195976
 
16 Naahidi S, Jafari M, Edalat F, Raymond K, Khademhosseini A, Chen P. Biocompatibility of engineered nanoparticles for drug delivery. J Controlled Rel. 2013;166:182-94. https://doi.org/10.1016/J.JCONREL.2012.12.013.
https://doi.org/10.1016/j.jconrel.2012.12.013
 
17 Rizvi SAA, Saleh AM. Applications of nanoparticle systems in drug delivery technology. Saudi Pharmaceutical J : SPJ. 2018;26:64. https://doi.org/10.1016/J.JSPS.2017.10.012.
https://doi.org/10.1016/j.jsps.2017.10.012
 
18 Delgado AV, López-Viota J, Ramos MM, Arias JL. Particle geometry, charge, and wettability: The fate of nanoparticle-based drug vehicles. Colloid and Interface Science in Pharmaceutical Research and Development 2014:443-67. https://doi.org/10.1016/B978-0-444-62614-1.00021-1.
https://doi.org/10.1016/B978-0-444-62614-1.00021-1
 
19 Liu Y, Yang G, Jin S, Xu L, Zhao CX. Development of high-drug-loading nanoparticles. Chempluschem. 2020;85:2143-57. https://doi.org/10.1002/CPLU.202000496.
https://doi.org/10.1002/cplu.202000496
 
20 Barzegar-Jalali M, Adibkia K, Valizadeh H, Shadbad MRS, Nokhodchi A, Omidi Y, et al. Kinetic analysis of drug release from nanoparticles. J Pharm Pharmaceut Sci 2008;11:167-77. https://doi.org/10.18433/J3D59T.
https://doi.org/10.18433/J3D59T
 
21 Karra N, Benita S. The ligand nanoparticle conjugation approach for targeted cancer therapy. Curr Drug Metab. 2011;13:22-41. https://doi.org/10.2174/138920012798356899.
https://doi.org/10.2174/138920012798356899
 
22 Subhan MA, Yalamarty SSK, Filipczak N, Parveen F, Torchilin VP. Recent advances in tumor targeting via EPR effect for cancer treatment. J Personalized Med. 2021;11:571. https://doi.org/10.3390/JPM11060571.
https://doi.org/10.3390/jpm11060571
 
23 Lopalco A, Denora N. Nanoformulations for drug delivery: Safety, toxicity, and efficacy. Methods Mol. Biol. 2018;1800:347-65. https://doi.org/10.1007/978-1-4939-7899-1_17.
https://doi.org/10.1007/978-1-4939-7899-1_17
 
24 Paliwal R, Babu RJ, Palakurthi S. Nanomedicine scale-up technologies: Feasibilities and challenges. AAPS PharmSciTech. 2014;15:1527. https://doi.org/10.1208/S12249-014-0177-9.
https://doi.org/10.1208/s12249-014-0177-9
 
25 Desai N. Challenges in development of nanoparticle-based therapeutics. AAPS J. 2012;14:282. https://doi.org/10.1208/S12248-012-9339-4.
https://doi.org/10.1208/s12248-012-9339-4
 
26 Jha S, Trivedi V, Deshmukh R. Approaches and molecular tools for targeted drug delivery in malaria infected red blood cells. Combination Drug Delivery Approach as an Effective Therapy for Various Diseases 2022:149-72. https://doi.org/10.1016/B978-0-323-85873-1.00014-9.
https://doi.org/10.1016/B978-0-323-85873-1.00014-9
 
27 Gulati M, Grover M, Singh S, Singh M. Lipophilic drug derivatives in liposomes. Int J Pharm 1998;165:129-68. https://doi.org/10.1016/S0378-5173(98)00006-4.
https://doi.org/10.1016/S0378-5173(98)00006-4
 
28 Liu P, Chen G, Zhang J. A review of liposomes as a drug delivery system: Current status of approved products, regulatory environments, and future perspectives. Molecules 2022;27. https://doi.org/10.3390/MOLECULES27041372.
https://doi.org/10.3390/molecules27041372
 
29 Gao W, Hu CMJ, Fang RH, Zhang L. Liposome-like nanostructures for drug delivery. J Mater Chem B. 2013;1:6569-85. https://doi.org/10.1039/C3TB21238F.
https://doi.org/10.1039/c3tb21238f
 
30 Abraham SA, Waterhouse DN, Mayer LD, Cullis PR, Madden TD, Bally MB. The liposomal formulation of doxorubicin. Methods Enzymol. 2005;391:71-97. https://doi.org/10.1016/S0076-6879(05)91004-5.
https://doi.org/10.1016/S0076-6879(05)91004-5
 
31 Rauchhaus U, Schwaiger FW, Panzner S. Separating therapeutic efficacy from glucocorticoid side-effects in rodent arthritis using novel, liposomal delivery of dexamethasone phosphate: Long-term suppression of arthritis facilitates interval treatment. Arthritis Res Ther. 2009;11:1-9. https://doi.org/10.1186/AR2889/FIGURES/5.
https://doi.org/10.1186/ar2889
 
32 Yoon G, Park JW, Yoon IS. Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs): Recent advances in drug delivery. J Pharm Investig. 2013;43:353-62. https://doi.org/10.1007/S40005-013-0087-Y/METRICS.
https://doi.org/10.1007/s40005-013-0087-y
 
33 Croy SR, Kwon GS. Polymeric micelles for drug delivery. Curr Pharm Des. 2006;12:4669-84. https://doi.org/10.2174/138161206779026245.
https://doi.org/10.2174/138161206779026245
 
34 Akram MW, Jamshaid H, Rehman FU, Zaeem M, Khan J zeb, Zeb A. Transfersomes: A revolutionary nanosystem for efficient transdermal drug delivery. AAPS PharmSciTech. 2022;23:1-18. https://doi.org/10.1208/S12249-021-02166-9/METRICS.
https://doi.org/10.1208/s12249-021-02166-9
 
35 Rajera R, Nagpal K, Singh SK, Mishra DN. Niosomes: A controlled and novel drug delivery system. Biol Pharm Bull. 2011;34:945-53. https://doi.org/10.1248/BPB.34.945.
https://doi.org/10.1248/bpb.34.945
 
36 Zielinska A, Carreiró F, Oliveira AM, Neves A, Pires B, Nagasamy Venkatesh D, et al. Polymeric nanoparticles: Production, characterization, toxicology and ecotoxicology. Molecules 2020;25. https://doi.org/10.3390/MOLECULES25163731.
https://doi.org/10.3390/molecules25163731
 
37 Anda-Flores Y De, Rascón-Chu A, Campa-Mada AC, Lizardi-Mendoza J, Tanori-Cordova J, Carvajal-Millan E. Polysaccharides nanoparticles as oral drug delivery systems. Natural Polysaccharides in Drug Delivery and Biomedical Applications 2019:399-417. https://doi.org/10.1016/B978-0-12-817055-7.00017-0.
https://doi.org/10.1016/B978-0-12-817055-7.00017-0
 
38 Mi P. Stimuli-responsive nanocarriers for drug delivery, tumor imaging, therapy and theranostics. Theranostics 2020;10:4557. https://doi.org/10.7150/THNO.38069.
https://doi.org/10.7150/thno.38069
 
39 Beach MA, Nayanathara U, Gao Y, Zhang C, Xiong Y, Wang Y, et al. Polymeric nanoparticles for drug delivery. Chem Rev. 2024;124:5505-616. https://doi.org/10.1021/ACS.CHEMREV.3C00705/ASSET/IMAGES/LARGE/CR 3C00705_0047.JPEG.
https://doi.org/10.1021/acs.chemrev.3c00705
 
40 Zhang H, Jin Y, Chi C, Han G, Jiang W, Wang Z, et al. Sponge particulates for biomedical applications: Biofunctionalization, multi-drug shielding, and theranostic applications. Biomaterials 2021;273:120824. https://doi.org/10.1016/J.BIOMATERIALS.2021.120824.
https://doi.org/10.1016/j.biomaterials.2021.120824
 
41 Shinde VR, Revi N, Murugappan S, Singh SP, Rengan AK. Enhanced permeability and retention effect: A key facilitator for solid tumor targeting by nanoparticles. Photodiagnosis Photodyn Ther. 2022;39:102915. https://doi.org/10.1016/J.PDPDT.2022.102915.
https://doi.org/10.1016/j.pdpdt.2022.102915
 
42 Snipstad S, Westrøm S, Mørch Y, Afadzi M, Åslund AKO, de Lange Davies C. Contact-mediated intracellular delivery of hydrophobic drugs from polymeric nanoparticles. Cancer Nanotechnol. 2014;5:1-18. https://doi.org/10.1186/S12645-014-0008-4/TABLES/2.
https://doi.org/10.1186/s12645-014-0008-4
 
43 Paul W, Sharma CP. Inorganic nanoparticles for targeted drug delivery. Biointegration of Medical Implant Materials 2020:333-73. https://doi.org/10.1016/B978-0-08-102680-9.00013-5.
https://doi.org/10.1016/B978-0-08-102680-9.00013-5
 
44 Shi Z, Zhou Y, Fan T, Lin Y, Zhang H, Mei L. Inorganic nanocarriers based smart drug delivery systems for tumor therapy. Smart Mater Med. 2020;1:32-47. https://doi.org/10.1016/J.SMAIM.2020.05.002.
https://doi.org/10.1016/j.smaim.2020.05.002
 
45 Unnikrishnan G, Joy A, Megha M, Kolanthai E, Senthilkumar M. Exploration of inorganic nanoparticles for revolutionary drug delivery applications: A critical review. Discover Nano 2023;18:1-44. https://doi.org/10.1186/S11671-023-03943-0.
https://doi.org/10.1186/s11671-023-03943-0
 
46 Rocha CV, Gonçalves V, da Silva MC, Bañobre-López M, Gallo J. PLGA-based composites for various biomedical applications. Int J Mol Sci. 2022;23:2034. https://doi.org/10.3390/IJMS23042034.
https://doi.org/10.3390/ijms23042034
 
47 Mugaka BP, Hu Y, Ma Y, Ding Y. Surface modification of gold nanoparticles for targeted drug delivery. Surface Modification of Nanoparticles for Targeted Drug Delivery 2019:391-403. https://doi.org/10.1007/978-3-030-06115-9_20.
https://doi.org/10.1007/978-3-030-06115-9_20
 
48 Sheth RA, Wen X, Li J, Melancon MP, Ji X, Andrew Wang Y, et al. Doxorubicin-loaded hollow gold nanospheres for dual photothermal ablation and chemoembolization therapy. Cancer Nanotechnol. 2020;11:1-16. https://doi.org/10.1186/S12645-020-00062-8/FIGURES/6.
https://doi.org/10.1186/s12645-020-00062-8
 
49 Sun Y, Davis E. Nanoplatforms for targeted stimuli-responsive drug delivery: A review of platform materials and stimuli-responsive release and targeting mechanisms. Nanomaterials. 2021;11:746. https://doi.org/10.3390/NANO11030746.
https://doi.org/10.3390/nano11030746
 
50 Jampilek J, Kralova K. Advances in drug delivery nanosystems using graphene-based materials and carbon nanotubes. Materials. 2021;14:1059. https://doi.org/10.3390/MA14051059.
https://doi.org/10.3390/ma14051059
 
51 Karki Y, Verma SS, Naz F. Biological nanomaterials and their development. 2023:69-90. https://doi.org/10.1007/978-981-99-4149-0_4.
https://doi.org/10.1007/978-981-99-4149-0_4
 
52 Rout SR, Gowtham K, Sheikh A, Parvez S, Dandela R, Kesharwani P. Recent advances and future prospective of hybrid drug delivery systems. Hybrid Nanomater Drug Deliv. 2022:357-74. https://doi.org/10.1016/B978-0-323-85754-3.00006-X.
https://doi.org/10.1016/B978-0-323-85754-3.00006-X
 
53 Yusuf A, Almotairy ARZ, Henidi H, Alshehri OY, Aldughaim MS. Nanoparticles as drug delivery systems: A review of the implication of nanoparticles’ physicochemical properties on responses in biological systems. Polymers. 2023;15:1596. https://doi.org/10.3390/POLYM15071596.
https://doi.org/10.3390/polym15071596
 
54 A new concept for macromolecular therapeutics in cancer chemotherapy: Mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs – PubMed n.d. https://pubmed.ncbi.nlm.nih.gov/2946403/ (accessed August 24, 2024).
 
55 Zi Y, Yang K, He J, Wu Z, Liu J, Zhang W. Strategies to enhance drug delivery to solid tumors by harnessing the EPR effects and alternative targeting mechanisms. Adv Drug Deliv Rev. 2022;188:114449. https://doi.org/10.1016/J.ADDR.2022.114449.
https://doi.org/10.1016/j.addr.2022.114449
 
56 Patra JK, Das G, Fraceto LF, Campos EVR, Rodriguez-Torres MDP, Acosta-Torres LS, et al. Nano based drug delivery systems: Recent developments and future prospects. J Nanobiotechnol. 2018;16:1-https://doi.org/10.1186/S12951-018-0392-8.
https://doi.org/10.1186/s12951-018-0392-8
 
57 Bellotti E, Cascone MG, Barbani N, Rossin D, Rastaldo R, Giachino C, et al. Targeting cancer cells overexpressing folate receptors with new terpolymer-based nanocapsules: Toward a novel targeted DNA delivery system for cancer therapy. Biomedicines 2021;9. https://doi.org/10.3390/BIOMEDICINES9091275.
https://doi.org/10.3390/biomedicines9091275
 
58 Wei H, Cui J, Lin K, Xie J, Wang X. Recent advances in smart stimuli-responsive biomaterials for bone therapeutics and regeneration. Bone Res. 2022;10:1-19. https://doi.org/10.1038/s41413-021-00180-y.
https://doi.org/10.1038/s41413-021-00180-y
 
59 Jauregui R, Srinivasan S, Vojtech LN, Gammill HS, Chiu DT, Hladik F, et al. Temperature-responsive magnetic nanoparticles for enabling affinity separation of extracellular vesicles. ACS Appl Mater Interfaces 2018;10:33847-56. https://doi.org/10.1021/ACSAMI.8B09751.
https://doi.org/10.1021/acsami.8b09751
 
60 Shaikh R, Raj Singh T, Garland M, Woolfson A, Donnelly R. Mucoadhesive drug delivery systems. J Pharm Bioallied Sci. 2011;3:89. https://doi.org/10.4103/0975-7406.76478.
https://doi.org/10.4103/0975-7406.76478
 
61 Omidian H, Gill EJ, Dey Chowdhury S, Cubeddu LX. Chitosan nanoparticles for intranasal drug delivery. Pharmaceutics. 2024;16:746. https://doi.org/10.3390/PHARMACEUTICS16060746.
https://doi.org/10.3390/pharmaceutics16060746
 
62 Cui F, Qian F, Yin C. Preparation and characterization of mucoadhesive polymer-coated nanoparticles. Int J Pharm. 2006;316:154-61. https://doi.org/10.1016/J.IJPHARM.2006.02.031.
https://doi.org/10.1016/j.ijpharm.2006.02.031
 
63 Barthelmes J, Perera G, Hombach J, Dünnhaupt S, Bernkop-Schnürch A. Development of a mucoadhesive nanoparticulate drug delivery system for a targeted drug release in the bladder. Int J Pharm. 2011;416:339-45. https://doi.org/10.1016/J.IJPHARM.2011.06.033.
https://doi.org/10.1016/j.ijpharm.2011.06.033
 
64 Shen Z, Nieh MP, Li Y. Decorating nanoparticle surface for targeted drug delivery: Opportunities and challenges. Polymers. 2016;8:83. https://doi.org/10.3390/POLYM8030083.
https://doi.org/10.3390/polym8030083
 
65 Pasut G. Grand challenges in nano-based drug delivery. Front Med Technol. 2019;1:501667.
https://doi.org/10.3389/fmedt.2019.00001
https://doi.org/10.3389/FMEDT.2019.00001/BIBTEX.
 
66 Patra JK, Das G, Fraceto LF, Campos EVR, Rodriguez-Torres MDP, Acosta-Torres LS, et al. Nano based drug delivery systems: Recent developments and future prospects. J Nanobiotechnol. 2018;16:1-33. https://doi.org/10.1186/S12951-018-0392-8.
https://doi.org/10.1186/s12951-018-0392-8
 
67 Hristova-Panusheva K, Xenodochidis C, Georgieva M, Krasteva N. Nanoparticle-mediated drug delivery systems for precision targeting in oncology. Pharmaceuticals (Basel). 2024;17. https://doi.org/10.3390/PH17060677.
https://doi.org/10.3390/ph17060677
 
68 Paul S, Mukherjee S, Banerjee P. Recent advancement in nanomaterial-encapsulated drug delivery vehicles for combating cancer, COVID-19, and HIV-like chronic diseases. Mater Adv. 2023;4:2042-61. https://doi.org/10.1039/D2MA01075E.
https://doi.org/10.1039/D2MA01075E
 
69 Klippstein R, Pozo D. Nanotechnology-based manipulation of dendritic cells for enhanced immunotherapy strategies. Nanomedicine 2010;6:523-9. https://doi.org/10.1016/J.NANO.2010.01.001.
https://doi.org/10.1016/j.nano.2010.01.001
 
70 Sajja HK, East MP, Mao H, Wang AY, Nie S, Yang L. Development of multifunctional nanoparticles for targeted drug delivery and non-invasive imaging of therapeutic effect. Curr Drug Discov Technol. 2009;6:43. https://doi.org/10.2174/157016309787581066.
https://doi.org/10.2174/157016309787581066
 
71 Mazayen ZM, Ghoneim AM, Elbatanony RS, Basalious EB, Bendas ER. Pharmaceutical nanotechnology: From the bench to the market. Futur J Pharm Sci 2022;8:12. https://doi.org/10.1186/S43094-022-00400-0.
https://doi.org/10.1186/s43094-022-00400-0
 
72 Silva GA. Nanotechnology approaches to crossing the blood-brain barrier and drug delivery to the CNS. BMC Neurosci. 2008;9:1-4. https://doi.org/10.1186/1471-2202-9-S3-S4/METRICS.
https://doi.org/10.1186/1471-2202-9-S3-S4
 
73 Chowdhury A, Kunjiappan S, Panneerselvam • Theivendren, Somasundaram • Balasubramanian, Chiranjib Bhattacharjee. Nanotechnology and nanocarrier-based approaches on treatment of degenerative diseases. Int Nano Lett. 2017;7:91-122. https://doi.org/10.1007/S40089-017-0208-0.
https://doi.org/10.1007/s40089-017-0208-0
 
74 Gunasekaran T, Haile T, Nigusse T, Dhanaraju MD. Nanotechnology: An effective tool for enhancing bioavailability and bioactivity of phytomedicine. Asian Pac J Trop Biomed. 2014;4:S1.https://doi.org/10.12980/APJTB.4.2014C980
https://doi.org/10.12980/APJTB.4.2014C980

Cite this article as:
Raheem A. Nanotechnology in Biomaterials: Revolutionizing Drug Delivery Systems. Premier Journal of Engineering 2024:1;100001

Export to EndNote Export to Mendeley