GSCBPS 2024 0121
GSCBPS 2024 0121
GSCBPS 2024 0121
Mohammad Shoaib Shaikh Hamid, Pooja R. Hatwar *, Ravindrakumar L. Bakal and Nitin B. Kohale
Department of Pharmaceutics, Shri Swami Samarth Institute of Pharmacy, At Parsodi, Dhamangoan Rly, Dist -Amravati
(444709) Maharashtra, India.
Publication history: Received on 27 February 2024; revised on 13 April 2024; accepted on 16 April 2024
Abstract
Liposomes, as versatile lipid-based nanoparticles, have emerged as promising drug delivery systems in recent years.
This comprehensive review aims to provide an in-depth analysis of the advancements, challenges, and potential
applications of liposomes in drug delivery. The review covers various aspects of liposome-based drug delivery, including
their structure, formulation methods, advantages, limitations, and recent breakthroughs in the field. Furthermore, we
discuss the diverse range of drugs and therapeutic agents that can be encapsulated within liposomes, as well as their
clinical applications in targeting specific diseases.
1. Introduction
The Greak words 'Lipos' which means fat and 'Soma' that means body, was combined to form spherical concentric
vesicles called liposomes. Liposomes are round sac phospholipid molecules. It encloses a water droplet especially as
form artificially to carry drug into tissue membrane. Liposome is a nanoparticle (size-100nm) [1]. Liposome were first
described by Bangham in 1961, it turned into an accidental discovery in which he scattered the phosphatidyl choline
molecule in water, for the duration of this he located that the molecule was forming a closed bilayer shape having an
aqueous segment which were entrapped by means of a lipid bilayer[2]. Liposomes are useful because they act as carriers
for a variety of drugs and have potential therapeutic or other properties. Various carriers such as nanoparticles,
microparticles, polysaccharides, lectins, and liposomes can be used to target drug to a specific sites. Liposomal drug
delivery is gaining interest due to its contribution to various areas like drug delivery, cosmetics, and biological
membrane structure [3]. A liposome is a tiny bubble (vesicle), with a membrane composed of a phospholipid bilayer.
Membranes are usually made of phospholipids like phosphatidylet-hanolamine and phosphatidylcholine. Phospholipids
are amphiphilic with its polar head as hydrophilic and hydrocarbon tail as hydrophobic [4].
2.1. Phospholipids
Naturally occurring phospholipids used in liposome:
o Phosphatidylethanolamine
o Phosphatidylcholine
o Phsphatidylserine
2.2. Cholesterol
Cholesterol may be included into phospholipids membrane in very high awareness up to 1:1 or 2:1 molar ratios of
cholesterol to phospatidylcholine. Being an amphipathic molecule, cholesterol inserts into the membrane with its
hydroxyl group of cholesterol orientated towards the aqueous floor and aliphatic chain aligned parallel to the acyl chains
inside the center of the bilayers and additionally it growth the separation between choline head organizations and gets
rid of the everyday electrostatic and hydrogen bonding interaction [6].
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3. History of Liposomes
Liposomes were first discovered in the mid-1960s by British hematologist Dr. Alec D. Bangham [2]. He was studying the
structure of cell membranes and stumbled upon the liposome while using an electron microscope [5]. Liposomes are tiny
spherical structures made up of lipid bilayers, similar to the structure of cell membranes. Dr. Bangham's
groundbreaking work laid the foundation for understanding and developing liposomes for various applications [8].
In the following decades, liposomes gained recognition for their potential in drug delivery. Their ability to encapsulate
drugs and transport them to specific sites in the body revolutionized the field of pharmacology [9]. Liposomal drug
delivery systems allowed for controlled release and reduced side effects of many medications [10].
Since then, liposomes have found applications not only in drug delivery but also in cosmetics, food technology, and gene
therapy. [11] Researchers have developed various types of liposomes with different sizes, compositions, and surface
modifications to optimize their performance for specific applications [11,12,13].
Today, liposomes continue to be an essential tool in the fields of medicine and biotechnology, with ongoing research
aimed at improving their effectiveness and versatility in delivering therapeutic agents and other bioactive compounds
[14,15,16].
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Uniformity: Achieving uniformity in liposome size and composition can be difficult, affecting their performance
and reproducibility.
Short Circulation Half-Life: Liposomes can be rapidly cleared from the bloodstream by the body's immune
system, limiting their time window for drug delivery.
Immunogenicity: Some liposome formulations may trigger an immune response, potentially causing adverse
reactions in the body.
Limited Drug Loading: Liposomes have a finite capacity for drug loading, which can be a limitation when trying
to deliver high doses of certain drugs.
Complexity: The development of liposomal formulations requires expertise and can be a complex process,
which may limit their accessibility to researchers and manufacturers.
Expense: Producing liposomal formulations can be costly, which may lead to higher drug prices for liposome-
based therapies.
Compatibility Issues: Some drugs may not be suitable for encapsulation in liposomes due to compatibility issues,
limiting the range of drugs that can benefit from liposomal delivery.
Clinical Translation: Despite promising results in preclinical studies, not all liposome-based therapies have
successfully transitioned to clinical use, highlighting challenges in translating laboratory findings to real-world
applications.
Interaction with Biological Systems: Liposomes may interact with proteins or cells in ways that affect their
stability, drug release, or performance.
Biodegradability: Depending on their composition, liposomes may not be readily biodegradable, which can
raise environmental concerns.
Niche Applications: Liposomes may not be suitable for all drug delivery needs, and alternative delivery systems
may be preferred in certain cases.
Release Control: Achieving precise control over drug release kinetics from liposomes can be challenging, which
may be critical for some therapeutic applications [20].
Regulatory Approval: Obtaining regulatory approval for liposomal drug products can be a complex and time-
consuming process, adding to the development timeline and cost [21].
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Endocytosis – This take location via phagocytic cells of reticuloendothelial system together with neutrophils.
Adsorption – It occurs to the cellular surface through non precise electrostatic forces or by using interplay with
cell surface additives.
Fusion- It takes place by means of the insertion of liposomal bilayer into plasma membrane with continuous
release of liposomal content into the cytoplasm.
Lipid exchange- on this transfer of liposomal lipids to the cellular membrane without association of liposomal
contents.
Steps:
Dissolve lipids (phospholipids and cholesterol) in an organic solvent like chloroform or methanol to create a
lipid solution.
Evaporate the solvent under reduced pressure to form a thin lipid film on the walls of a round-bottom flask or
a glass vial.
Hydrate the lipid film by adding an aqueous solution (e.g., buffer or distilled water) and vortexing or sonicating
to form multilamellar vesicles (MLVs).
Optionally, you can reduce the size of MLVs to smaller unilamellar vesicles (SUVs) through extrusion or
sonication.
Steps:
Dissolve lipids in an organic solvent along with an aqueous solution containing the substance to be
encapsulated.
Evaporate the organic solvent under reduced pressure to form a water-in-oil emulsion.
Remove the organic phase, leaving behind liposomes containing the encapsulated substance.
Steps:
Steps:
Prepare liposomes using the thin-film hydration method or another appropriate method.
Subject the liposome suspension to high-frequency ultrasound (sonication) to reduce the size of the liposomes.
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Steps:
Steps:
Freeze the liposome suspension at a low temperature, typically below the lipid's phase transition temperature.
Thaw the frozen suspension at a higher temperature, repeating the cycle multiple times.
This process helps to entrap substances within liposomes and reduce leakage.
Morphology
Transmission Electron Microscopy (TEM): Provides high-resolution images of liposome size, shape, and
lamellarity.
Scanning Electron Microscopy (SEM): Offers surface information and morphology details.
Electrophoretic Light Scattering: Determines the surface charge of liposomes, which affects stability and
colloidal behavior.
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Encapsulation Efficiency
UV-Visible Spectroscopy or Fluorescence Spectroscopy: Measures the concentration of encapsulated drugs or
molecules.
Stability:
Assessing changes in size, poly dispersity, and zeta potential over time under various storage conditions (e.g.,
temperature, pH).
In vivo Studies
Animal models to evaluate the pharmacokinetics, biodistribution, and therapeutic efficacy of liposomal drug
formulations.
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5.2.5. Diagnostics:
Liposomes can serve as carriers for contrast agents in medical imaging, such as magnetic resonance imaging
(MRI) and ultrasound.
They enable targeted imaging of specific tissues or cells.
5.2.8. Biotechnology
Liposomes are used in research and biotechnology applications for drug screening and delivery to cells in vitro.
They are valuable tools for studying cell membrane interactions and drug transport mechanisms.
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Targeted Drug Delivery: Liposomes can be designed to target specific tissues or cells, which can enhance the
therapeutic efficacy of drugs while minimizing side effects. This targeted drug delivery is particularly important
for treating diseases like cancer, where precision in drug delivery is crucial. [59]
Personalized Medicine: Liposomes can be customized to encapsulate different drugs and combinations of drugs,
allowing for personalized treatment regimens. This could revolutionize healthcare by tailoring drug therapies
to individual patient needs.
Co-Delivery of Therapeutics: Liposomes can carry multiple drugs simultaneously, making them suitable for co-
delivery of synergistic therapeutic agents. This approach can improve treatment outcomes for various diseases
and conditions.
Controlled Release: Liposomes can be engineered to release drugs in a controlled and sustained manner,
extending the therapeutic effect and reducing the frequency of dosing. This is especially valuable for chronic
conditions.
Vaccine Delivery: Liposomes have shown promise as carriers for vaccines. They can enhance the stability and
immunogenicity of antigens, potentially leading to the development of more effective vaccines for infectious
diseases.
Gene Therapy: Liposomes can be used to deliver genetic material, such as small interfering RNA (siRNA) or
CRISPR-Cas9 components, to target cells for gene therapy applications. This holds great potential for treating
genetic disorders.
Crossing Biological Barriers: Liposomes can be modified to overcome biological barriers, such as the blood-
brain barrier, facilitating the delivery of drugs to the central nervous system for the treatment of neurological
disorders.
Combination Therapies: Liposomes can be used to combine different therapeutic modalities, such as
chemotherapy and immunotherapy, for synergistic effects in cancer treatment.
Improvements in Formulation: Ongoing research aims to enhance liposomal formulations by improving
stability, reducing toxicity, and increasing drug-loading capacity, which will expand their utility.
Regulatory Approvals: As more liposome-based drug delivery systems undergo clinical trials and gain
regulatory approvals, their use in healthcare will likely become more widespread.
6. Conclusion
Liposomes represent a promising and innovative drug delivery system with a wide range of applications in the field of
pharmaceuticals. Over the years, extensive research has demonstrated their potential to overcome various challenges
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associated with traditional drug delivery methods. Liposomes have emerged as a promising class of drug delivery
systems that offer significant advantages for enhancing the therapeutic efficacy and safety of various drugs. While
challenges remain, the continued innovation and refinement of liposomal technologies hold great promise for the future
of drug delivery in the pharmaceutical industry. Liposomes represent an exciting and versatile approach to drug
delivery, with the potential to revolutionize the pharmaceutical industry by improving drug efficacy, reducing side
effects, and enabling precise targeting of therapies. Further advancements in liposomal technology are likely to expand
their use in a wide range of medical applications.
References
[1] Sawant GS, Sutar KV, Kanekar AS. Liposome: A Novel Drug Delivery System. International Journal of Research
and Review. 2021; 8(4): 252-268.
[2] Mishra H, Chauhan V, Kumar K, Teotia D. A Comprehensive review on Liposomes: a novel drug delivery system.
Journal of Drug Delivery and Therapeutics. 2018; 8(6): 400-404.
[3] Sharma D, Ali AAE, Trivedi LR. An Updated Review on: Liposomes as drug delivery system. PharmaTutor. 2018;
6(2):50-62.
[4] Dhandapani N, Thapa A, Goti S, Bhattara. R. Liposomes as novel drug delivery system: A comprehensive review,
Nagasamy Venkatesh Dhandapani Int. J. Res. Pharm Sci. 2013; 4(2):187-193.
[5] Dr. Tiwari,Talreja S & Ms Swarnima Pandey. A review on use of novel drug delivery systems in herbal medicines,
Science and Engineering Journal. 2020; 24(8):190-197.
[6] Dwivedi C, Yadav R, Tiwari S, T. Satapathy. Roy A, Role of Liposome in novel drug delivery systems. Journal of
Drug Delivery & Therapeutics; 2014; 4(2):116-129.
[7] Sudhakark, Shivkanya, Fuloria, Subramaniyan V. Kathiresan V. Sathasivam. Review Ultraflexible Liposome
Nanocargo as a Dermal and Transdermal Drug Delivery System.Nanomaterials. 2021; 11; 2557.
[8] A. D. Bangham. Liposome: The Babraham Connection. Chemistry and Physics of Lipids. 1993; 64:1-3.
[9] Bangham A. D, Standish M. M, Weissmann G. The action of steroids and streptolysins on the permeability of
phospholipid structures to cations. Journal of Molecular Biology. 1965; 13(1): 253-259.
[10] Touitou, E. Drug delivery across the skin. Expert Opin. Biol. Ther. 2002; 2: 723–733.
[11] Abd El-Alim, S. H.; Kassem, A. A. Basha, M.; Salama, A. Comparative study of liposomes, ethosomes and
transfersomes as carriers for enhancing the transdermal delivery of diflunisal. In vitro and in vivo evaluation. Int.
J. Pharm. 2019; 563, 293–303.
[12] Ramadon, D. Mc Crudden, M. T. C. Courtenay, A. J. Donnelly, R. F. Enhancement strategies for transdermal drug
delivery systems. Current trends and applications. Drug Deliv. Transl. Res.2022 12(4):758-791.
[13] Trucillo, P. Campardelli, R.Reverchon, E. Liposomes: From Bangham to Supercritical Fluidss. Processes 2020; 8:
1022. 1-15.
[14] Arora, D. Nanda, S. Quality by design driven development of resveratrol loaded ethosomal hydrogel for improved
dermatological benefits via enhanced skin permeation and retention. Int. J. Pharm. 2019; 567: 118448.
[15] Weissig, V. Liposomes Came First. The Early History of Liposomology. Methods Mol. Biol. 2017; 1522: 1–15.
[16] Taglietti, M. Hawkins, C. N. Rao, J. Novel Topical Drug Delivery Systems and Their Potential Use in Acne Vulgaris.
Skin Ther. Lett. 2008; 13: 2.6-8.
[17] Gomez-Hens, A. Fernandez-Romero, J. M. Analytical methods for the control of liposomal delivery systems.
Trends Anal Chem, 2006; 25:167–178.
[18] Meiwan Chen Yanfang Zhou, Jingjing Huang, Ping Zhu, Xinsheng Peng, and Yitao Wang. Liposome-Based Delivery
Systems in Plant Polysaccharides. Journal of Nanomaterials. 2012; 12: 1-4.
208
GSC Biological and Pharmaceutical Sciences, 2024, 27(01), 199–210
[19] Nalawade V, Patil K. International Journal of Publication and Review. 2023; 4(1):1795-1801.
[20] Tianshu Lian, Rodney J. Y. HO. Trends and Developments in Liposome Drug Delivery Systems. Jounral of
pharmaceutical sciences. 2001; 90(6): 667-680.
[21] Pradhan, N. Kumar, S. Saha, et al. Liposome: Method of preparation, advantages, evaluation and its application.
Journal of Applied Pharmaceutical Research. 2015; 3(3): 1-8.
[22] Gabrijelcic V, Sentjure M and Kristl J. Evaluation of liposomes as drug carriers into the skin by one di-mensional
EPR imaging. Int J Pharm. 1990; 62: 75-79.
[23] Cabral E. C. M, Zollner R. L. And Santana M. H. A. Brazilian Journal of Chemical Engineering Preparation And
Characterization Of Liposmes Entrapping Allergenic Protein Received: 2004, 21, (02): 137 - 146.
[24] Bangham, A.D. and R.W. Horne. Negative staining of phospholipids and their structured by surface active agents
as observed in the electron microscope. J. Mol. Biol. 1964; 8: 660–668.
[25] Kaur D. Kumar S. Niosomes: present scenario and future aspects. Journal of Drug Delivery and Therapeutics,
2018; 8(5):35-43.
[26] Hong MS. Prolonged blood circulation of methotrexate by modulation of liposomal composition. Drug Delivery
.2001; 8: 231–237.
[27] Jesorka A, al. Liposomes: technologies and analytical applications, Annu. Rev. Anal. Chem. 2008; 1: 801–832.
[28] Vemuri S, et al. Preparation and characterization of liposomes as therapeutic delivery systems: a review, Pharm.
Acta Helv. 1995; 70: 95–111.
[29] Shailesh S, Neelam S, Sandeep K, Gupta GD. Liposomes: A review. Journal of Pharmacy Research.2009; 2(7):1163-
1167.
[30] Godbole MD, Mathur VB. Selection of phospholipid and method of formulation for optimum entrapment and
release of lamivudine from liposome. Journal of Drug Delivery and Therapeutics. 2018; 8(5-s):175-183.
[31] Kaur D, Kumar S. Niosomes: present scenario and future aspects. Journal of Drug Delivery and Therapeutics.
2018; 8(5) 35-43.
[32] Kirby C, Gregoriadis G. Dehydration-Rehydration Vesicles: Simple Method for High Yield Drug Entrapment in
Liposomes. Biotechnology 2, 1984, 2: 979–984.
[33] Rahman A, Uahengo V, Likius D. Mini review on emerging methods of preparation of liposome and its application
as Liposome drug delivery systems. Open J Pharmacol Pharmacother. 2018; 3(1): 005-021.
[34] John F. Deeken, Rebecca Slack, Phase I trial in advanced malignancies with liposome encapsulated paclitaxel
(LEP).Cancer Chemother Pharmacol. 2013; 71(3): 627–633.
[35] Riaz Mohammad. Review Liposomes Preparation Method Pakistan Journal of Pharmaceutical Sciences.1996;
19(1): 65-77.
[36] Dwivedi. C, Yadav. R Tiwari. S.P, Liposome: a Powerful Approach for Vesicular Drug Delivery System, Elixir
Pharmacy 81 (2015) 31461-31474.
[37] Rajan K. Verma and Sanjay Garg, “Current Status of Drug Delivery Technologies and Future Directions.”
Pharmaceutical Technology" On-Line. 2001; 25 (2), 1–14.
[38] Dwivedi Chandraprakash, Verma. Review on Preparation and Characterization of Liposomes with Application.
Journal of Scientific & Innovative Research. 2013; 2 (2): 1-31.
[39] Bangham AD, Standish MM, Watkin JC. Diffusion of univalent ions across the lamellae of swollen phospholipids.
J, Mol, Biol. 1965; 13: 238-252.
[40] Zili Gu, Candido G. Da Silva, Koen van der Maaden, Ferry Ossendorp and Luis J. Cruz. Liposome-Based Drug
Delivery Systems in Cancer Immunotherapy. Pharmaceutics, 2020; 12.1-25.
[41] B. Pradhan, N. Kumar, S. Saha, et al. Liposome: Method of preparation, advantages, evaluation and its application.
Journal of Applied Pharmaceutical Research. 2015; 3(3): 1-8.
[42] Caponigro F, Cornelia P, Budillon A. Phase I study of Caelyx (doxorubicin HCL, Pegylated liposomal) in recurrent
or metastatic head and neck cancer. Annals of Oncology. 2000; 11(3): 339-342.
209
GSC Biological and Pharmaceutical Sciences, 2024, 27(01), 199–210
[43] L. Kaur, P. Kaur, and MU. Khan. Liposome as a drug carrier- A review. International Journal of Research in
Pharmacy and Chemistry. 2013; 3(1): 16.121-128.
[44] Ramkrishna S, Sunit K. S, Soumyaranjan S. Liposome as drug delivery system: A brief review. International
Journal of Research in Pharmaceutical Science. 2014; 5(4): 309-321.
[45] S. Marripati, K. Umashankar, P. Jayachandra Reddy. A Review on Liposomes. International Journal of Research in
Pharmaceutical and Nanoscience. 2014; 3(3): 159-169.
[46] Shashi K. Satinder K.Bharat P. A Complete Review on Liposome. International Research Journal of Pharmacy.
2012; 3(7): 10-16.
[47] Keller, B.C. Liposomes in Nutrition. Trends Food Sci. Technol. 2001; 12: 25–31.
[48] Rao M, Alving CR. Delivery of lipids and liposomal proteins to the cytoplasm and Golgi of antigen-presenting cells.
Advance Drug Delivery Review. 2000; 41: 171-188.
[49] Lian T, Bui T, Ho RJ. Formulation of HIV-envelope protein with lipid vesicles expressing ganglioside GM1
associated to cholera toxin B enhances mucosal immune responses Vaccine .1999; 18:604-611.
[50] Bui T, Dykers, T, Hu SL, Faltynek CR, Ho RJ. Effect of MTP-PE liposomes and interleukin-7 on induction of antibody
and cell-mediated immuneresponses to a recombinant HIV-envelope protein. J Acquir Immune De®c Syndr .
1994; 7: 799-806.
[51] Gluck R. Liposomal presentation of antigens for human vaccines. Pharm Biotechnol. 1995; 6: 325-345.
[52] Gabrijelcic V and Sentjure M. Influence of hydrogel on liposome stability and on liposome stability and on the
transport of liposome entrapped substance in to the skin. Int J Pharm .1995; 118: 209-212.
[53] Johnston MJ, Semple SC, Klimuk SK, Ansell S, Maurer N, Cullis. PR: Characterization of the drug retention and
pharmacokinetic properties of liposomal nanoparticles containing dihydrosphingomyelin. Biochim Biophys Acta.
2007; 1768:1121–1127.
[54] Atrooz OM. Effects of alkylresorcinolic lipids obtained from acetonic extract of Jordanian wheat grains on
liposome properties. Int J Biol Chem. 2011; 5(5): 314–321.
[55] Hatwar P. R, Dr. Bakal R. L, Dumare A. A, Dere M. D, Hage. P. D, Targeted drug delivery system for the treatment
of Cancer, WJPR. 2023; 12(12): 808-816.
[56] Deulkar D. A, kubade J. A, Hatwar P. R, Dr. Bakal R. L. A review on transdermal drug delivery system, GSC Advances
Research and Reviews. 2024; 18(02): 347-361.
[57] Liu W., Ye A., Singh H. Progress in Applications of Liposomes in Food Systems. In Microencapsulation and
Microspheres for Food Applications; Elsevier: Amsterdam. The Netherlands. 2015; 151–170.
[58] Shashi K., Satinder K., Bharat P. A Complete Review on Liposome. International Research Journal of Pharmacy.
2012; 3(7): 10-16.
[59] Bagmar N. A, Hatwar P. R, Dr. Bakal R. L. A review on Targeted Drug Delivery System, WJPR. 2023; 12(19): 288-
298.
[60] http://images.app.goo.gl/uV9HszgnHjLtcEgH9
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