Prerpints.org logo
Preprint
Review

Advancements in Liposomal and Nanoparticle-Based Targeted Drug Delivery

This version is not peer-reviewed.

Submitted:

18 March 2025

Posted:

19 March 2025

You are already at the latest version

Abstract
Targeted drug delivery systems have become revolutionary in therapy with increased effectiveness and reduced side effects compared to traditional practice. Liposomal and nanoparticle carriers are among the very effective nanoplatforms with controlled delivery, site-directed drug concentration, and enhanced therapeutic outcomes. Transformation of drug delivery from traditional systems to nanocarrier systems is presented herein with emphasis on mechanisms, advantages, and medical applications. Liposomal nanocarriers are bioavailable and stable, while nanoparticles are tumor-specific drug delivery systems based on smart and responsive platforms. Eco-friendly and biodegradable materials in drug design also lead to drug safety and biocompatibility improvements.One of the key characteristics of modern nanomedicine is its ability to leverage the tumor microenvironment, and in particular the EPR effect, to deliver drug concentration in cancer tissue. Biological barriers, however, are problematic, and as such new strategies such as surface engineering and enzyme-sensitive nanoparticles must be used to increase penetration and therapeutic effect. Although these present some issues, long-term nanotechnology research can assist in improving drug delivery methods and treatment to become individualized and effective. The present review is a summary of existing innovation in liposomal and nanoparticle-based drug delivery, their role in precision medicine and the treatment of cancer, and how they have potential to revolutionize.
Keywords: 
Liposomal drug delivery
;  
Nanoparticles
;  
Targeted therapy
;  
Tumor microenvironment
;  
Stimuli-responsive nanocarriers
Subject: 
Medicine and Pharmacology  -   Pharmacy

1. Introduction to Targeted Drug Delivery

Targeted drug delivery revolutionized contemporary medicine by eliminating the limitations of conventional drug delivery. Traditional processes have the propensity of causing grand-scale distribution of the drugs, accountable for off-target toxicity and poor efficacy. Targeted drug delivery systems, as opposed to others, localize the drugs at the target site with increased therapeutic activity and least possible systemic toxicity. Combination of nanotechnology with carriers further optimized the process to promote controlled drug discharge and increased bioavailability [1].
Drug delivery through nanoparticles has been a promise in the past few decades, with the use of nanoscale carriers to deliver drugs directly to tissue. From liposomes to polymeric nanoparticles and biopolymers, these carriers have improved circulation time, lowered immune clearance, and greater cellular uptake [2]. Material science and bioengineering advances further propel these systems, moving them toward precision medicine.

1.1. Evolution from Conventional to Nanoparticle-Based Delivery

Earlier drug delivery systems included passive diffusion and systemic delivery and were made to release suboptimal amounts of the drug to the target location. Inefficiency of this nature necessitated regular dosing and raised the prospect of side effects. Trends away from nanoparticle-based systems with higher drug transport, overcoming physiological barriers, and with sustained release [1] have been reported.
Nanoparticles provide structural modification to improve drug solubility, stability, and specificity. Functionalization processes provide the means of surface modification to allow nanoparticles to evade immune recognition and maintain circulation [2]. These technologies have been widely used in cancer treatment, where drug-concentrating nanoparticles localize to tumor tissue with limited action on normal tissue.

1.2. Importance of Precision Medicine and Targeted Therapy

Precision medicine aims at personalizing the treatment based on the patient’s profile so that therapeutic agents attack the disease or condition specifically with maximum efficacy and minimal side effects. Nanocarriers fulfill this by way of site-specific drug delivery with no systemic toxicity and maximum compliance of the patient [3].
Targeted drugs are very effective in drug delivery in cancer therapy with ligand drug delivery, where nanoparticles have been employed to bind and target particular cell receptors. Targeted mechanism prolongs the residence time of the drug in the tumor tissue and reduces exposure in normal tissues [4]. Apart from this, biodegradable nanobiopolymers have established environmentally friendly drug carriers to offer maximum therapeutic effectiveness and reduce long-term toxicity complications [5].
Table 1. Importance of Precision Medicine and Targeted Therapy.
Table 1. Importance of Precision Medicine and Targeted Therapy.
Aspect Description Key Benefits Reference
Precision Medicine Tailors treatment based on patient-specific factors Maximizes efficacy, minimizes side effects [3]
Nanocarriers in Drug Delivery Enables site-specific drug release with minimal systemic toxicity Improves patient compliance, reduces toxicity [3]
Targeted Cancer Therapy Uses ligand-drug delivery to bind specific cell receptors Enhances drug accumulation at tumor sites [4]
Biodegradable Nanopolymers Environmentally friendly drug carriers for safer therapies Reduces long-term toxicity and complications [5]

2. Liposomal and Nanoparticle-Based Drug Delivery Systems

Application of nanoparticles and liposomes in designing drug delivery systems has been the key to enhancing drug selectivity and efficiency.
Table 2. Liposomal and Nanoparticle-Based Drug Delivery Systems.
Table 2. Liposomal and Nanoparticle-Based Drug Delivery Systems.
Aspect Liposomal Drug Delivery Nanoparticle-Based Drug Delivery
Biocompatibility High; composed of phospholipid bilayers Varies; depends on material (polymeric, metal, lipid)
Drug Encapsulation Hydrophilic (core) & hydrophobic (bilayer) drugs Tunable for various drugs, including hydrophobic
Bioavailability Improved due to sustained drug release Enhanced retention and circulation
Targeted Delivery Achievable through PEGylation and ligand modifications Highly tunable for active targeting
Applications Cancer therapy, infectious diseases, gene therapy Cancer, chronic diseases, regenerative medicine

2.1. Mechanisms and Advantages of Liposomal Nanocarriers

Liposomal drug carriers operate by the entrapment of the therapeutic agents in lipid bilayers to protect them from enzymatic hydrolysis and increase the stability of the drug in the bloodstream. The carriers may be designed for passive or active targeting to provide delivery of the drug to target tissues with decreased side effects [6]. The ability of liposomes to increase drug solubility and facilitate drugs with sustained release has made them useful tools in disease treatment such as cancer and infection diseases.
Progress in liposomal nanocarriers has seen the development of PEGylated liposomes with longer circulatory half-lives by evading the immune system. Drug levels at desired locations are increased, promoting more effective therapy [7]. Ligand-functionalized liposomes are being developed for targeted delivery with the aim of improved drug delivery strategies.
Table 3. Mechanisms, Advantages, and Applications of Liposomal and Nanoparticle Drug Carriers.
Table 3. Mechanisms, Advantages, and Applications of Liposomal and Nanoparticle Drug Carriers.
Category Liposomal Nanocarriers Nanoparticle-Based Drug Delivery Reference
Mechanism of Action Entraps drugs in lipid bilayers for stability & protection Allows drug loading via polymeric, dendrimer, or inorganic structures [6]
Targeting Approaches Passive (EPR effect) & active (ligand-functionalized liposomes) Active targeting via aptamers, surface ligands, and functional coatings [7]
Immune System Evasion PEGylation extends circulation time Surface modifications reduce immune recognition [7]
Solubility Enhancement Increases solubility of hydrophobic drugs Improves solubility and stability of poorly soluble drugs [8]
Sustained Release Prolongs drug action via controlled release Engineered for slow, controlled drug release [8]
Applications Cancer therapy, infectious diseases, gene therapy Cancer, regenerative medicine, personalized therapy [9]
Recent Innovations Ligand-functionalized liposomes for enhanced targeting Aptamer-functionalized nanoparticles for precision targeting [10]
Theranostic Potential Imaging-integrated liposomes for tracking treatment response Multifunctional nanoparticles for simultaneous therapy and imaging [11]

2.2. Clinical Applications and Recent Innovations in Nanoparticles

Nanoparticles have revolutionized the discipline of drug delivery because they allow specific delivery at the cellular level with high specificity. Polymeric nanoparticles, dendrimers, and inorganic nanocarriers have been explored extensively for their applicability in enhancing solubility along with sustaining controlled release [8]. Nanocarriers hold immense potential in cancer therapy, where drugs are entrapped to enhance tumor tissue accumulation with less systemic toxicity.
Some of the new trends in drug delivery using nanoparticles are aptamer-functionalized nanoparticles, which exhibit higher targeting specificity and therapeutic activity [9]. These bioconjugated nanoparticles have been found to deliver cancer chemotherapeutic drugs to the target cells with reduced side effects by in vivo studies [10]. Nanomedicine is also poised to use multifunctional nanoparticles with imaging and therapeutic properties to track the effect of the treatment in real time [11].

3. Nanotechnology in Cancer Treatment

3.1. Role of Nanocarriers in Tumor Targeting and Controlled Release

Nanocarriers enhance active and passive tumor targeting. The EPR effect enables the penetration of nanoparticles via the leaky vasculature of the tumor tissues, thereby localizing the drug at the target site [12]. Surface modification through the incorporation of ligands also enhances active targeting, hence drug molecules are conjugated to cancer cells with minimal effect on normal tissue.
Controlled drug release is among the most significant advantages of nanocarriers. Drug release may be formulated based on numerous conditions such as pH, temperature, or enzyme concentrations of the tumor microenvironment using the concept of stimulus-responsive nanoparticles [13]. Such action avoids prior degradation of the drug and enhances the therapeutic effect of the anticancer treatment.

3.2. Smart Drug Carriers and Enhanced Therapeutic Efficiency

Development in intelligent drug carriers has been improved to improve cancer therapy’s efficacy. Targeted nanocarriers attached with antibodies or with peptides, or ligands are extremely drug delivery selective in an attempt to reduce off-target toxicities and enhance response rates for patients [14]. Stimuli-responsive nanocarriers, for example, release drugs only if they encounter specific biological stimulants in order to deliver more targeted therapy.
The second new field involves light-responsive nanostructures that deliver drug therapeutics upon exposure to targeted light wavelengths. The intelligent nanostructures provide spatiotemporal control of drug delivery with lower side effects and greater efficacy [15]. Furthermore, multimodal functionalized nanoparticles combine drug delivery and imaging to monitor tumor progression and therapeutic response in real time [16].

4. Biodegradable and Sustainable Innovations in Drug Delivery

With the growing need for sustainability in the field of medicine, biodegradable drug delivery systems have been a successful alternative to traditional therapies. These systems ensure better biocompatibility, reduce long-term toxicity, and deliver drugs in controlled ways with eco-safety.

4.1. Stimuli-Responsive Nanocarriers (pH, Temperature, Enzyme)

Stimuli-sensitive nanocarriers have been developed in a way that they will release the drug upon exposure to the respective biological stimulus, thereby ensuring therapeutic selectivity. pH-sensitive carriers, for instance, are physiologically stable at the pH but are degraded by the acidic tumor tissue microenvironment and hence local release of the drug takes place [17]. Thermosensitive nanoparticles are also thermosensitive, and local delivery is attained in heat-treated tumor tissues [18]. Enzyme-activated systems constitute another major advance where the drug release is based on cancer-specific enzymes and therefore specificity of therapy is attained.

4.2. Sustainable Materials and Biocompatible Drug Delivery Systems

Progress in biodegradable nanocarriers has improved drug delivery efficacy and safety tremendously. Some of the environmentally friendly materials used like mesoporous silica nanoparticles, lipid vesicles, and polymeric micelles have increased biocompatibility in addition to controlled degradation characteristics that minimize systemic toxicity [19]. Nanotheranostics are multi-modal platforms where diagnostic and therapeutic components are integrated into a single platform, enabling targeted therapeutic regimens and thereby increasing the efficacy of drugs as well as patient outcome [20].

5. Exploiting the Tumor Microenvironment for Effective Therapy

5.1. Enhanced Permeability and Retention (EPR) Effect

EPR effect is one of the leading mechanisms utilized in nanomedicine by which nanoparticles get passively accumulated within the tumor as a result of leaky vasculature and compromised lymphatic drainage. EPR effect results in increased drug concentrations in cancer tissue in comparison to normal cells with higher efficacy and fewer side effects [21]. Nanoparticle preparations have also been rationally engineered by researchers to maximize the drug retention due to the EPR effect with the ideal size, charge, and surface chemistry to penetrate tumors [22].

5.2. Strategies for Overcoming Biological Barriers

In spite of the EPR effect advantage, high extracellular matrices and drug efflux pumps are biological barriers to nanoparticle entry. To overcome these limitations, new delivery systems utilize surface properties such as PEGylation and ligand-functionalization to enhance circulation times and selectivity in targeting [23]. Furthermore, enzyme-sensitive nanoparticles degrade extracellular barriers, enhancing tumor penetration and drug bioavailability.

Conclusion

The advancements brought in by liposomal and nanoparticle-based drug delivery technologies have revolutionized targeted therapy to a great extent. From their early days of existence outside conventional drug delivery avenues to formulation of precision medicine technology, these technologies have promoted drug stability, drug controlled release, and minimized systemic toxicity. Liposomal nanocarriers with biocompatibility and tunability assure proper encapsulation of drugs, and nanoparticles assure target site delivery of drugs, especially in cancer therapy.
Technologies including stimuli-responsive and biodegradable nanotechnology-based carriers further prolong the process of drug delivery due to the reaction to the temperature, pH, and enzymatic activity biological cues. Green matter is utilized that ensures biocompatibility and lesser side effects. Moreover, leverage of the tumor microenvironment through the EPR effect allows cancer tissues to achieve higher concentrations of drugs. Biological barriers do exist, though, and so there is a requirement to create surface-modified and ligand-targeted nanoparticles that will be able to penetrate and exert an effect.
Withstand record milestones aside, more work remains to render such drug delivery systems suitable for therapy. Next-generation research needs to be channeled towards nanoparticle stabilization, minimizing immunogenicity, and attaining customized treatment options. Further growth in nanomedicine promises to revolutionize drug delivery with improved, more efficacious, and less toxic medication for a large array of conditions, particularly cancer.

References

  1. Allen, T. M., & Cullis, P. R. (2004). Drug delivery systems: Entering the mainstream. Science, 303(5665), 1818-1822. https://doi.org/10.1126/science.1095833. [CrossRef]
  2. Zhang, L., Gu, F. X., Chan, J. M., Wang, A. Z., Langer, R., & Farokhzad, O. C. (2008). Nanoparticles in medicine: Therapeutic applications and developments. Clinical Pharmacology & Therapeutics, 83(5), 761-769. https://doi.org/10.1038/sj.clpt.6100400. [CrossRef]
  3. Sengar, A. (2025). Advancements in targeted drug delivery: Innovations in liposomal, nanoparticle, and vesicular systems. Preprints. https://doi.org/10.20944/preprints202502.1830.v1. [CrossRef]
  4. Petros, R. A., & DeSimone, J. M. (2010). Strategies in the design of nanoparticles for therapeutic applications. Nature Reviews Drug Discovery, 9(8), 615-627. https://doi.org/10.1038/nrd2591. [CrossRef]
  5. Gulati, S., Ansari, N., Moriya, Y., Joshi, K., Prasad, D., Sajwan, G., Shukla, S., Kumar, S., & Varma, R. S. (2024). Nanobiopolymers in cancer therapeutics: Advancing targeted drug delivery through sustainable and controlled release mechanisms. Journal of Materials Chemistry B, 12(46), 11887-11915. https://doi.org/10.1039/D4TB00599F. [CrossRef]
  6. Torchilin, V. P. (2005). Recent advances with liposomes as pharmaceutical carriers. Nature Reviews Drug Discovery, 4(2), 145-160. https://doi.org/10.1038/nrd1632. [CrossRef]
  7. Sengar, A. (2025). Liposomal nanocarriers from concept to clinical applications. Preprints. https://doi.org/10.20944/preprints202503.0837.v1. [CrossRef]
  8. Duncan, R. (2006). Polymer conjugates as anticancer nanomedicines. Nature Reviews Cancer, 6(9), 688-701. https://doi.org/10.1038/nrc1958. [CrossRef]
  9. Bajaj, G., & Davu, G. (2024). Nanotechnology-based drug delivery in cancer treatment: Enabling controlled and targeted release of medications. International Journal of Research in Medical Sciences, 12(9), 3522-3527. https://doi.org/10.18203/2320-6012.ijrms20242641. [CrossRef]
  10. Farokhzad, O. C., Cheng, J., Teply, B. A., Sherifi, I., Jon, S., Kantoff, P. W., Richie, J. P., & Langer, R. (2006). Targeted nanoparticle-aptamer bioconjugates for cancer chemotherapy in vivo. Proceedings of the National Academy of Sciences, 103(16), 6315-6320. https://doi.org/10.1073/pnas.0601755103. [CrossRef]
  11. Shi, J., Kantoff, P. W., Wooster, R., & Farokhzad, O. C. (2017). Cancer nanomedicine: Progress, challenges, and opportunities. Nature Reviews Cancer, 17(1), 20-37. https://doi.org/10.1038/nrc.2016.108. [CrossRef]
  12. Sengar, A. (2025). The role of nanotechnology in revolutionizing cancer treatment. Preprints. https://doi.org/10.20944/preprints202503.0713.v1. [CrossRef]
  13. Wang, X., Yang, L., Chen, Z. G., & Shin, D. M. (2008). Application of nanotechnology in cancer therapy and imaging. CA: A Cancer Journal for Clinicians, 58(2), 97-110. https://doi.org/10.3322/CA.2007.0003. [CrossRef]
  14. Sinha, R., Kim, G. J., Nie, S., & Shin, D. M. (2006). Nanotechnology in cancer therapeutics: Bioconjugated nanoparticles for drug delivery. Molecular Cancer Therapeutics, 5(8), 1909-1917. https://doi.org/10.1158/1535-7163.MCT-06-0141. [CrossRef]
  15. Karimi, M., et al. (2016). Smart nanostructures for cargo delivery: Uncaging and activating by light. Journal of the American Chemical Society, 138(16), 7226-7236. https://doi.org/10.1021/jacs.6b00318. [CrossRef]
  16. Sun, T., Zhang, Y. S., Pang, B., Hyun, D. C., Yang, M., & Xia, Y. (2014). Engineered nanoparticles for drug delivery in cancer therapy. Angewandte Chemie International Edition, 53(46), 12320-12364. https://doi.org/10.1002/anie.201403036. [CrossRef]
  17. Ashutosh, S. (2025). Sustainable drug delivery systems with biodegradable innovations for targeted and efficient therapy. Preprints. https://doi.org/10.20944/preprints202502.1489.v1. [CrossRef]
  18. Narayan, R., Nayak, U. Y., Raichur, A. M., & Garg, S. (2020). Mesoporous silica nanoparticles: A comprehensive review on synthesis and recent advances. Drug Delivery and Translational Research, 10(6), 1578-1618. https://doi.org/10.1007/s13346-020-00744-3. [CrossRef]
  19. Danhier, F., Feron, O., & Préat, V. (2010). To exploit the tumor microenvironment: Passive and active tumor targeting of nanocarriers. Journal of Controlled Release, 148(2), 135-146. https://doi.org/10.1016/j.jconrel.2010.08.027. [CrossRef]
  20. Mura, S., & Couvreur, P. (2012). Nanotheranostics for personalized medicine. Advanced Drug Delivery Reviews, 64(13), 1394-1416. https://doi.org/10.1016/j.addr.2012.06.006. [CrossRef]
  21. Maeda, H., Wu, J., Sawa, T., Matsumura, Y., & Hori, K. (2000). Tumor vascular permeability and the EPR effect in macromolecular therapeutics: A review. Journal of Controlled Release, 65(1-2), 271-284. https://doi.org/10.1016/S0168-3659(99)00248-5. [CrossRef]
  22. Peer, D., Karp, J. M., Hong, S., Farokhzad, O. C., Margalit, R., & Langer, R. (2007). Nanocarriers as an emerging platform for cancer therapy. Nature Nanotechnology, 2(12), 751-760. https://doi.org/10.1038/nnano.2007.387. [CrossRef]
  23. Emerich, D. F., & Thanos, C. G. (2006). The pinpoint promise of nanoparticle-based drug delivery and molecular diagnosis. Biomolecular Engineering, 23(4), 171-184. https://doi.org/10.1016/j.bioeng.2006.05.021. [CrossRef]
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.
Copyright: This open access article is published under a Creative Commons CC BY 4.0 license, which permit the free download, distribution, and reuse, provided that the author and preprint are cited in any reuse.

Downloads

63

Views

53

Comments

0

Subscription

Notify me about updates to this article or when a peer-reviewed version is published.

Email

Prerpints.org logo

Preprints.org is a free preprint server supported by MDPI in Basel, Switzerland.

facebook logotwitter logolinkedin logo
MDPI Initiatives
Important Links
Subscribe

Disclaimer

Terms of Use

Privacy Policy

© 2025 MDPI (Basel, Switzerland) unless otherwise stated