INTRODUCTION:

Liposomes are defined as spherical vesicles with particle sizes ranging from 30 nm to several micrometers. They consist of one or more lipid bilayers surrounding aqueous units, where the polar head groups are oriented in the pathway of the interior and exterior aqueous phases. Depend on molecular shape, temperature, and environmental and preparation conditions but may self-assemble into various types of colloidal particles⁽¹⁾. Due to complexicity of tumours, an effective penetration of anticancer agents encapsulated within nano carrier is the main challenge in cancer therapy.⁽²⁾

Liposomes are most commly investigated nano structure used in advanced drug delivery which were first discovered by Alee Bangham in 1963.⁽³⁾ Two of the greatest hurdles towards achieving cures with traditional chemotherapeutics are systemic toxicity and bioavailability at the tumor site (i.e., free drug is toxic to normal cells and achieves peak plasma concentrations in only 5 minutes.)⁽⁴⁾. In order to enhance the biodistribution of these drugs, reduce free drug toxicity, and favor tumor accumulation, drug delivery research have principally focused on phospholipid-based liposomes.^(5,6,7) Nanocarriers have larger surface area as compared to other systems, which can be easily modified to encapsulate large amount of drug which will increase the blood circulation time and enhance the accumulation of drugs in solid tumors via the enhanced permeability and retention (EPR) effect as well as selective targeting of tumor cells.⁽⁸⁾ Liposomes have several advantages contributing to drug delivery. They have a role enhancing drug solubility⁽⁹⁾, serving as a sustained release system^(10),providing targeted drug delivery^(11), reducing the toxic effect of drugs⁽¹²⁾, providing protection against drug degradation^(13), enhancing circulation half-life of APIs⁽¹⁴⁾, being effective in overcoming multidrug resistance⁽¹⁵⁾, improving the therapeutic index of the entrapped drug⁽¹⁶⁾, and protecting APIs against their surrounding environment ⁽¹⁷⁾

CATEGORY:

Numerous factors define liposomes properties such as the lipid composition, number of lipid bilayers, size, surface charge, and the method of preparation⁽¹⁸⁾_. Liposomes have been utilized to improve the restorative file of new or set up drugs by changing medication assimilation, lessening digestion, dragging out natural half-life or diminishing poisonousness. Medication conveyance is then controlled essentially by properties of the bearer and no longer by physico-compound qualities of the medication substance as it were. Lipids framing liposomes might be characteristic or engineered, and liposome constituents are most certainly not elite of lipids, new age liposomes can likewise be framed from polymers (in some cases alluded to as polymersomes). ⁽¹⁹⁾ The one of a kind element of liposomes is their capacity to compartmentalize and solubilize both hydrophilic and hydrophobic materials commonly. This one of a kind element, combined with biocompatibility and biodegradability make liposomes extremely appealing as medication conveyance vehicles. Liposome restricting drugs into or onto their layers, are relied upon to be shipped without quick corruption and minimum reactions to the beneficiary in light of the fact that by and large liposomes are made out of biodegradable, organically dormant and non-immunogenic lipids.⁽²⁰⁾ Thus, all these properties just as the simplicity of surface alteration to shoulder the targetable properties make liposomes increasingly appealing possibility for use as medication conveyance vehicles than other medication conveying frameworks.^(21,22)

MECHANISM:

The limitations and blessings of liposome drug carriers lie critically on the interplay of liposomes with cellsand their destiny in vivo after administration. In vivo and in vitro studies of the contacts with cells have shown that the primary interplay of liposomes with cells both easy adsorption (by means of precise interactions with cellular-surface components, electrostatic forces, or by way of nonspecific susceptible hydrophobic) or following endocytosis (by means of phagocytic cells of the reticuloendothelial device, as an instance macrophages and neutrophils)⁽²³⁾ Fusion with the plasma cell membrane by using insertion of the liposome of the lipid bilayer into the plasma membrane, with simultaneous release of liposomal content into the cytoplasm, is a lot uncommon⁽²⁴⁾ The fourth possible interplay is the trade of bilayer additives, for instance cholesterol, lipids, and membrane-sure molecules with additives of cellular membranes. It is often difficult to determine what mechanism is functioning, and more than one may characteristic at the same time.⁽²⁵⁾

STRUCTURE OF LIPOSOME:

Figure 1. Structure of conventional and functionalised liposomes: (A) conventional liposomes comprising phospholipids; (B) PEGylated/stealth liposomes containing a layer of polyethylene glycol (PEG); (C) targeted liposomes containing a specific ligand to target a cancer site; and (D) multifunctional liposomes, which can be used for diagnosis and treatment of solid tumours. Adapted from Creative Commons Attribution License.⁽²⁶⁾

STRUCTURAL STABILITY:

Physical and chemical stability of the liposomes in terms of size distribution, entrapment efficiency, and minimal degradation of liposomal apparatuses is the major limiting step for drug delivery using this system. Chemical degradation of liposomes mainly occurs at the phospholipid bilayers level, in which two different reactions might develop: (i) hydrolysis of the ester bonds between fatty acids and glycerol backbone, and (ii) peroxidation of any available unsaturated acyl chain. These two reactions might lead to the development of short-chain lipids; subsequently, soluble derivatives will appear in the membrane that would significantly reduce the quality and stability of the liposomal system⁽²⁷⁾ Several factors that have an influence on liposomal system stability, such as liposomal composition (e.g., phospholipids-lipids with high phase transition temperatures), fatty acid side-chains, polar head chemistry, chain length, and the degree of unsaturation, are preferred to maintain liposomal rigidity⁽²⁸⁾ and phospholipid:cholesterol molar ratio (crucial for the liposomal stability and controlling drug release). Briuglia et al. (2015) demonstrated that 70:30 molar ratio of phospholipids (using 1,2-Dimyristoyl-sn-glycero-3-phosphocholine (DMPC), dipalmitoyl phosphatidylcholine (DPPC), and distearoyl phosphatidylcholine (DSPC)): cholesterol achieved a liposomal formulation that can guarantee the stability and control over drug release⁽²⁹⁾ and surface potential (high surface potential is directly related to the liposomal physical stability, as it helps to reduce the rate of fusion and aggregation^(30). The physical stability of liposomes improves by increasing the surface charge density and reducing the ionic strength of liposomes (increases the electrostatic repulsive energies), especially when phosphatidylcholine and phosphatidylserine are used ^(31,32) Electrostatic stabilisation can be improved by combining it with the steric stabilisation (so called electrosteric stabilisation), which can be obtained by covering the surface of the liposomes with an adsorbed coat of long, bulky molecules (which, for example, keep the distance between the vesicles)⁽³³⁾

LIPOSOMAL COMPOSITION:

The maximum recognized lipids used within the liposomal formulations are phosphatidylcholine (zwitterionic), phosphatidylglycerol (negatively charged), phosphatidic acid, phosphatidylethanolamine (zwitterionic), and phosphatidylserine (negatively charged). Positively charged lipids (e.G., N-[1-(2,3-dioleyloxy) propyl]-N,N,N-triethylammonium(DOTMA) and 1,2-dioleoyl-three-trimethylammoniopropane (DOTAP)) are specially used for gene delivery, as they have interaction with the negatively charged deoxyribonucleic acid (DNA)⁽³⁴⁾ and negatively charged APIs.

Cholesterol is some other strategic aspect of liposomes. It has a modulatory impact at the properties of the lipid bilayer of the liposomes.⁽³⁵⁾Cholesterol is likewise vital for structural stability of liposomal membranes against intestinal environmental pressure.⁽³⁶⁾ Cholesterol become observed to influence liposomes length (increasing ldl cholesterol concentration increases liposomes size further to form transition), offer permeability and fluidity, and consequently modulate the discharge of hydrophilic compounds from liposomes.⁽³⁷⁾

METHODS OF PREPARATION:

There are a few parameters that should be considered during the method selection: 1) the physicochemical characteristics of the material to be entrapped and those of the liposomal ingredients, 2) the nature of the medium in which the liposomes are dispersed, 3) the effective concentration of the encapsulated material and its potential toxicity, 4) additional processes involved during application (delivery of the liposomes), 5) optimum size, polydispersity and shelf-life of the liposomes for the intended application and 6) batch-to-batch reproducibility and possibility of large-scale production of safe and efficient liposomal products^(38-40)

1.Mechanical dispersion method. 2.Solvent dispersion method. 3.Detergent removal method (removal of nonencapsulated material)^(41-42)

1. Mechanical dispersion method:

a. Sonication: Sonication is perhaps the most extensively used method for the preparation of SUV. Here, MLVs are sonicated either with a bath type sonicator or a probe sonicator under a passive atmosphere. The main disadvantages of this method are very low internal volume/encapsulation efficacy, possible degradation of phospholipids and compounds to be encapsulated, elimination of large molecules, metal pollution from probe tip, and presence of MLV along with SUV⁽⁴³⁾. There are two sonication techniques:

· Probe sonication. The tip of a sonicator is directly engrossed into the liposome dispersion. The energy input into lipid dispersion is very high in this method. The coupling of energy at the tip results in local hotness; therefore, the vessel must be engrossed into a water/ice bath. Throughout the sonication up to 1 h, more than 5% of the lipids can be deesterified. Also, with the probe sonicator, titanium will slough off and pollute the solution.

· Bath sonication. The liposome dispersion in a cylinder is placed into a bath sonicator. Controlling the temperature of the lipid dispersion is usually easier in this method, in contrast to sonication by dispersal directly using the tip. The material being sonicated can be protected in a sterile vessel, dissimilar the probe units, or under an inert atmosphere⁽⁴⁴⁾

2. Solvent dispersion method:

In this type of preparation methods, lipids are first dissolved in an organic solvent and then brought into contact with the aqueous phase containing the materials to be encapsulated within the liposome. The lipids align themselves into a monolayer at the interface between the organic and aqueous phase which is an important step to form the bilayer of the liposome⁽⁴⁵⁾

a. Ether injection (solvent vaporization): A solution of lipids dissolved in diethyl ether or ether-methanol mixture is gradually injected to an aqueous solution of the material to be encapsulated at 55°C to 65°C or under reduced pressure. The consequent removal of ether under vacuum leads to the creation of liposomes. The main disadvantages of the technique are that the population is heterogeneous (70 to 200 nm) and the exposure of compounds to be encapsulated to organic solvents at high temperature ⁽⁴⁶⁾

3. Detergent removal method:

a. Dialysis: The detergents at their critical micelle concentrations (CMC) have been used to solubilize lipids. As the detergent is detached, the micelles become increasingly better-off in phospholipid and lastly combine to form LUVs. The detergents were removed by dialysis. A commercial device called LipoPrep (Diachema AG, Switzerland), which is a version of dialysis system, is obtainable for the elimination of detergents. The dialysis can be performed in dialysis bags engrossed in large detergent free buffers (equilibrium dialysis)⁽⁴⁷⁾

LIPOSOMES IN ANTICANCER THERAPY:

Surgical resection, radiation therapy and chemotherapy are the first-line treatment of cancer. The chemotherapeutic agent can then be up taken via cancer and normal tissues, leads to severe toxicity to exclusive body organs such as heart, kidneys, liver and others.⁽⁴⁸⁾The success of cancer treatment basically depends on its capability to reduce the size and remove tumours without affecting normal tissues, thus increasing patients’ survival time and enhancing their quality of life.⁽⁴⁹⁾ The encapsulation of chemotherapeutic agents within liposomal structures can reduce the normal tissue uptake of the drug and thus improve its therapeutic index.⁽⁵⁰⁾ cancer cells and tumour related tissues overexpress certain types of receptor such as TFR, Folate receptor and antigens compared with the heathy cells.^(51-52) By means of passive targeting and active targeting liposomes can concentrate preferentially on the tumour.⁽⁵³⁾

LIPOSOMAL TARGETING:

Various strategies have been adopted for targeting liposomes to the tumour sites.⁽⁵⁴⁾Liposome concentrated on to tumor tissues may be broadly labeled into two types – passive targeting and active targeting.⁽⁵⁵⁾

Passive targeting:

passive targeting of liposomes is done by transferring them into the tumour interstitium via leaky tumour vasculature.⁽⁵⁶⁾The size of the gaps between the endothelial cells lining the tumor capillaries(interstitial space) ranges from 100 to 780nm depending on the cancer type, as that in a typical normal endothelium of 5–10nm.⁽⁵⁷⁾ Targeting of the drugs depending on the pathophysiological properties of the tumor tissues is referred to as ‘passive drug targeting’.⁽⁵⁸⁾ There is limited circulatory recovery of the extravasated molecules, resulting in the accumulation of nanoparticles in the tumor microenvironment. This phenomenon leads to a nano-particle accumulation in the tumor microenvironment which has been termed as the enhanced permeability and retention (EPR) effect.^(59-60) Utilization of the EPR effect is an effective strategy for targeting liposomes to the tumour site. Unlike liposomes and other nanoparticles, low molecular weight drugs and they are not retained in the tumor site for a longer period of time since they re-enter the circulation primarily via diffusion.^(61-62) An additional targeting method has been developed that uses an external trigger to overcome this problem. This can be done by triggering the release of the chemotherapeutic agent within the interstitium after accumulating on the tumour tissue. This can be achieved by releasing the agent within the tumour vasculature using liposomes particularly designed to respond to a precise external trigger (e.g., heat) . For example thermosensitive liposomes that can be administered systemically were developed.^(63-64)

Active targeting:

liposomes are actively targeted to tumour cells by surface modification. In general, actively targeted liposomes are designed to minimize adrift effects. Actively targeted liposomal systems are prepared by conjugating targeting moieties, including ligands, peptides and monoclonal antibodies, on the liposomal surface.⁽⁶⁵⁾ For example, certain receptors, such as folate and transferrin (Tf) receptors (TfR), are over expressed on cancer cells and can used to make liposomes tumor cell specific.⁽⁶⁶⁾ also, Liposomes can actively target tumour tissues using the antibody-based approach. It is done by incorporating certain antibodies to the liposomal surface. It is called as immunoliposomes (ILP).⁽⁶⁷⁾ Moreover, these surface-modified liposomes can further enhance intracellular uptake when they reach the tumor interstitium, presumably by several endocytotic pathway⁶⁸

APPLICATION OF LIPOSOME:

The most successful applications of liposomes in cancer therapeutics are PEGylated liposomal formulation and it is the first liposomal product that was approved by the FDA for the treatment of kaposi’s sarcoma in AIDS patients. ⁽⁷⁰⁾A liposomal formulation of cytarabine and daunorubicin.it showed promising results in phase III clinical trial on the patients with secondary acute myeloid leukemia (AML) by improving the induction response over 40%. ⁽⁷¹⁾

Table 1. Liposomal formulations used as anticancer treatments. ^(72-75)

Active Ingredient	Liposome Composition	Size (nm)	Cancer Type Being Targeted
DOX	HSPC/DSPE/cholesterol (12.5:1:8.25 molar ratio)	130	Colorectal
PCX	Egg phosphatidylcholine: cholesterol: TPGS1000-TPP (molar ratio 88:3.5:8.5)	80	Lung cancer cell lines
MXT	HSPC: DSPE-PEG2000: cholesterol: anacardic acid (molar ratio 0.55:0.05:0.35:0.05)	112	Melanoma cell lines
ATRA	DOTAP, cholesterol and ATRA (molar ratio 70:20:10)	263	Lung cancer

CONCLUSION:

Liposomes were the first nanotechnology-based drug delivery systems approved for the clinical applications in cancer therapy because of their biocompatibility and biodegradability features. Liposomes overcome the limitations of conventional chemotherapy by improving the stability of the drug molecules hence it is one of the popular agent in cancer therapy. However, based on the pharmaceutical applications and their available products, we can say that liposomes have definitely established their position in modern delivery systems and it will be developing more in future.

REFERENCE:

1. Andreas W, Karola VU: Liposome technology for industrial purposes. J Drug Deliv 201:9.

2. Takechi-haraya Y, Goda Y., Sakai Kato K. Control of Liposomal penetration into three dimensional multicellular tumour spheroid by modulating liposomal membrane rigidity. Mol. Pharma.2017;14:2158-2165.

3. Bangham A.D. Physical structure and behavior of lipids and lipids enzyme. Adv.Lipid Res. 1963;1:65-104.

4. Rahman A, Carmichael D, Harris M, Roh JK. Comparative pharmacokinetics of free doxorubicin and doxorubicin entrapped in cardiolipin liposomes. Cancer Res. 1986;46: 2295–2299.

5. Davis AJ, Tannock IF. Tumor physiology and resistance to chemotherapy: repopulation and drug penetration. Cancer Treat Res. 2002; 112:1–26.

6. Minchinton AI, Tannock IF. Drug penetration in solid tumours. Nat Rev Cancer. 2006;6: 583–592.

7. Papahadjopoulos D, editor. Liposomes and their uses in biology and medicine. New York: Annals of the New York Academy of Sciences; 1978.

8. Tyagi N and Ghosh PC. Folate receptor mediated targeted delivery of ricin entrapped into sterically stabilized liposomes to human epidermoid carcinoma (KB) cells: effect of monensin intercalated into folate-tagged liposomes. Eur J Pharm Sci. 2011; 43: 343-353.

9. Mohammed, A.R.; Weston, N.; Coombes, A.G.A.; Fitzgerald, M.; Perrie, Y. Liposome formulation of poorly water soluble drugs: optimisation of drug loading and ESEM analysis of stability. Int. J. Pharm. 2004, 285, 23–34.

10. Mukherjee, B.; Patra, B.; Layek, B.; Mukherjee, A. Sustained release of acyclovir from nano-liposomes and nano-niosomes: An in vitro study. Int. J. Nanomed. 2007, 2, 213–225.

11. Allen, T.M. Long-circulating (sterically stabilized) liposomes for targeted drug delivery. Trends Pharmacol. Sci. 1994, 15, 215–220.

12. Allen, T.M.; Martin, F.J. Advantages of liposomal delivery systems for anthracyclines. Semin. Oncol. 2004, 31, 5–15.

13. Cristiano, M.C.; Cosco, D.; Celia, C.; Tudose, A.; Mare, R.; Paolino, D.; Fresta, M. Anticancer activity of all-trans retinoic acid-loaded liposomes on human thyroid carcinoma cells. Colloids Surf. B: Biointerfaces 2017, 150, 408–416.

14. Allen, T.M.; Cheng, W.W.; Hare, J.I.; Laginha, K.M. Pharmacokinetics and pharmacodynamics of lipidic nano-particles in cancer. Anticancer Agents Med. Chem. 2006, 6, 513–523.

15. Matsuo, H.; Wakasugi, M.; Takanaga, H.; Ohtani, H.; Naito, M.; Tsuruo, T.; Sawada, Y. Possibility of the reversal of multidrug resistance and the avoidance of side effects by liposomes modified with MRK-16, a monoclonal antibody to P-glycoprotein. J. Control. Release 2001, 77, 77–86.

16. Wang, C.X.; Li, C.L.; Zhao, X.; Yang, H.Y.; Wei, N.; Li, Y.-H.; Zhang, L.; Zhang, L. Pharmacodynamics, pharmacokinetics and tissue distribution of liposomal mitoxantrone hydrochloride. Yao Xue Xue Bao 2010, 45, 1565–1569.

17. Park, K.; Kwon, I.C.; Park, K. Oral protein delivery: Current status and future prospect. React. Funct. Polym. 2011, 71, 280–287.

18. Akbarzadeh, A.; Rezaei-Sadabady, R.; Davaran, S.; Joo, S.W.; Zarghami, N.; Hanifehpour, Y.; Samiei, M.; Kouhi, M.; Nejati-Koshki, K. Liposome: Classification, preparation, and applications. Nanoscale Res. Lett. 2013, 8, 102.

19. Gregoriadis G, Florene A. T. Liposomes in Drug Delivery: Clinical, Diagnostic and Opthalmic Potential. Drugs 1993;45 15-28.

20. Campbell P.I. Toxicity of Some Charged Lipids Used in Liposome Preparations. Cytobios 1983;37 (1983) 21-26.

21. Grislain L, Couvreur P, Lenaerts V, Roland M, Depreg-Decampeneere D, Speiser P. Pharmacokinetics and Distribution of a Biodegradable Drug-carrier. International Journal of Pharmacology 1983;15 335-338.

22. Illum L, Gones P.D.E, Kreuker J, Daldwin R.W, Davis D.D. Adsorption of Monoclonal Antibodies to Polyhexylcyanoacrylate Nanoparticles and Subsequent Immunospecific Binding to Tumor Cells. International Journal of Pharmacology 1983;1765-69

23. Babai I, Samira S, Barenholz Y, Zakay-Rones Z, Kedar E: A novel influenza subunit vaccine composed of liposome-encapsulated haemagglutinin/ neuraminidase and IL-2 or GM-CSF. I. Vaccine characterization and efficacy studies in mice. Vaccine 1999, 17:1223–1238.

24. Banerjee R, Tyagi P, Li S, Huang L: Anisamide-targeted stealth liposomes: a potent carrier for targeting doxorubicin to human prostate cancer cells. Int J Cancer 2004, 112:693–700.

25. Baselga J, Metselaar JM: Monoclonal antibodies: clinical applications: monoclonal antibodies directed against growth factor receptors. In Principles and Practice of Biological Therapy of Cancer. Edited by Rosenburg SA. Philadelphia: Lippincott; 2000:475–489

26. Riaz, M.K.; Riaz, M.A.; Zhang, X.; Lin, C.; Wong, K.H.; Chen, X.; Zhang, G.; Lu, A.; Yang, Z. Surface functionalization and targeting strategies of liposomes in solid tumor therapy: A review. Int. J. Mol. Sci. 2018, 19, 195.

27. Yadav, A.; Murthy, M.S.; Shete, A.S.; Sakhare, S. Stability aspects of liposomes. Indian J. Pharm. Educ. Res. 2011, 45, 402–413.

28. Ceh, B.; Lasic, D.D. A rigorous theory of remote loading of drugs into liposomes. Langmuir 1995, 11, 3356–3368.

29. Briuglia, M.-L.; Rotella, C.; McFarlane, A.; Lamprou, D.A. Influence of cholesterol on liposome stability and on in vitro drug release. Drug Deliv. Transl. Res. 2015, 5, 231–242.

30. Crommelin, D.J. Influence of lipid composition and ionic strength on the physical stability of liposomes. J. Pharm. Sci. 1984, 73, 1559–1563.

31. Crommelin, D.J. Influence of lipid composition and ionic strength on the physical stability of liposomes. J. Pharm. Sci. 1984, 73, 1559–1563.

32. Frokjaer, S.; Hjorth, E.L.; Worts, O. Stability and storage of liposomes. In Optimization of Drug Delivery; Bundgaard, H., Bagger Hansen, A., Kofod, H., Eds.; Munkgaard: Copenhagen, Denmark, 1982.

33. Yadav, A.; Murthy, M.S.; Shete, A.S.; Sakhare, S. Stability aspects of liposomes. Indian J. Pharm. Educ. Res. 2011, 45, 402–413

34. Munye M.M., Ravi J., Tagalakis A.D., McCarthy D., Ryadnov M.G., Hart S.L. Role of liposome and peptide in the synergistic enhancement of transfection with a lipopolyplex vector. Sci. Rep. 2015;5: 9292.

35. Briuglia M.-L., Rotella C., McFarlane A., Lamprou D.A. Influence of cholesterol on liposome stability and on in vitro drug release. Drug Deliv. Transl. Res. 2015;5: 231–242.

36. Liu W., Wei F., Ye A., Tian M., Han J. Kinetic stability and membrane structure of liposomes during in vitro infant intestinal digestion: Effect of cholesterol and lactoferrin. Food Chem. 2017;230-242.

37. Kaddah S., Khreich N., Kaddah F., Charcosset C., Greige-Gerges H. Cholesterol modulates the liposome membrane fluidity and permeability for a hydrophilic molecule. Food Chem. Toxicol. 2018;113: 40–48.

38. Gomez-Hens A, Fernandez-Romero J. M. Analytical Methods for the Control of Lipo‐ somal Delivery Systems. Trends in Analytical Chemistry 2006;25 167-178.

39. Mozafari M.R, Johnson C, Hatziantoniou S, Demetzos C. Nanoliposomes and Their Applications in Food Nanotechnology. Journal of Liposome Research 2008;18 309-327.

40. Dua J.S, Rana A.C, Bhandari A.K. Liposome: Methods of Preparation and Applica‐ tions. International Journal of Pharmaceutical Studies and Research 2012;3(2) 14-20.

41. Riaz M: Liposome preparation method. Pak J Pharm Sci 1996, 9(1):65–77.

42. Himanshu A, Sitasharan P, Singhai AK: Liposomes as drug carriers. IJPLS 2011, 2(7):945–951.

43. Riaz M: Liposome preparation method. Pak J Pharm Sci 1996, 9(1):65–77.

44. Kataria S, Sandhu P, Bilandi A, Akanksha M, Kapoor B, Seth GL, Bihani SD: Stealth liposomes: a review. IJRAP 2011, 2(5):1534–1538

45. Rickwood D, Hames BD. Liposomes: A Practical Approach. IRL Press; 1994

46. Schieren H, Rudolph S, Findelstein M, Coleman P, Weissmann G: Comparison of large unilamellar vesicles prepared by a petroleum ether vaporization method with multilamellar vesicles: ESR, diffusion and entrapment analyses. Biochim Biophys Acta 1978, 542(1):137–153

47. Shaheen SM, Shakil Ahmed FR, Hossen MN, Ahmed M, Amran MS, Ul-Islam MA: Liposome as a carrier for advanced drug delivery. Pak J Biol Sci 2006, 9(6):1181–1191.

48. Motamarry, A.; Asemani, D.; Haemmerich, D. Thermosensitive Liposomes. In Liposomes; Catala, A., Ed.; InTech: Rijeka, Croatia, 2017.

49. Gogoi, M.; Kumar, N.; Patra, S. Multifunctional magnetic liposomes for cancer imaging and therapeutic applications. In Nanoarchitectonics Smart Delivery Drug Targeting; Holban, A.M.,Grumezescu, G., Eds.; Elsevier: Amsterdam, The Netherlands, 2016; pp. 743–782.

50. Maeda, H. The enhanced permeability and retention (EPR) effect in tumor vasculature: The key role of tumor-selective macromolecular drug targeting. Adv. Enzyme Regul. 2001, 41, 189–207.

51. Kaasgaard T, Andresen TL. Liposomal cancer therapy: exploiting tumor characteristics. Expert Opin. Drug Deliv.2010,7(2), 225–243.

52. Moghimipour E, Rezaei M, Ramezani Z et al. Folic acid-modified liposomal drug delivery strategy for tumortargeting of 5-fluorouracil. Eur. J. Pharm. Sci. 2010, 114, 166–174.

53. Maeda, H. The enhanced permeability and retention (EPR) effect in tumor vasculature: The key role of tumor-selective macromolecular drug targeting. Adv. Enzyme Regul. 2001, 41, 189–207.

54. _{Voinea M, Simionescu M. Designing of}‘intelligent’ liposomes for efficient delivery of drugs. J. Cell. Mol. Med. 6(4), 465–474 (2002).

55. Bradley AJ, Devine DV, Ansell SM, Janzen J, Brooks DE. Inhibition of liposome-induced complement activation by incorporated poly(ethylene glycol)-lipids. Arch Biochem Biophys1998; 357: 185-94.

56. Gogoi, M.; Kumar, N.; Patra, S. Multifunctional magnetic liposomes for cancer imaging and therapeutic applications. In Nanoarchitectonics Smart Delivery Drug Targeting; Holban, A.M. Grumezescu, G., Eds.; Elsevier: Amsterdam, The Netherlands, 2016; pp. 743–782.

57. Haley B, Frenkel E. Nanoparticles for drug delivery in cancer treatment. Urol. Oncol2008, . 26(1), 57–64.

58. Torchilin V. Passive and active drug targeting: drug delivery to tumors as an example. Handb. Exp. Pharmacol. (2010).197, 3–53

59. Torchilin V. Tumor delivery of macromolecular drugs based on the EPR effect. Adv. Drug. Deliv. Rev. (2011). 63(3), 131–135

60. Torchilin VP. Drug targeting. Eur. J. Pharm. Sci. 11, (2000). S81–S91

61. Kale AA, Torchilin VP. Environment responsive multifunctional liposomes. Methods Mol. Biol. 605, (2010). 213–242

62. Maeda H. Macromolecular therapeutics in cancer treatment: the EPR effect and beyond. J. Control. Release(2012), 164(2), 138–144

63. Motamarry, A.; Asemani, D.; Haemmerich, D. Thermosensitive Liposomes. In Liposomes; Catala, A.,Ed.; InTech: Rijeka, Croatia, 2017.

64. Kunjachan, S.; Ehling, J.; Storm, G.; Kiessling, F.; Lammers, T. Noninvasive imaging of nanomedicines and nanotheranostics: Principles, progress, and prospects. Chem. Rev. 2015, 115,10907–10937.

65. Torchilin VP. Targeted pharmaceutical nanocarriers for cancer therapy and imaging. AAPS J. (2007). 9(2), 128–147.

66. Taleka M, Kendall J, Denny W, Garg s, Targeting of nanoparticles in cancer: drug delivery and diagnostics. Anticancer Drugs (2011)., 22(10), 949

67. Targeting of nanoparticles in cancer: drug delivery and diagnostics. Anticancer Drugs (2011)., 22(10), 949

68. Kunjachan, S.; Ehling, J.; Storm, G.; Kiessling, F.; Lammers, T. Noninvasive imaging of nanomedicines and nanotheranostics: Principles, progress, and prospects. Chem. Rev. 2015, 115,10907–10937.

69. Noble GT, Stefanick JF, Ashley JD, Kiziltepe T, Bilgicer B. Ligand-targeted liposome design: challenges andfundamental considerations. Trends Biotechnol. (2014). 32(1), 32–45

70. Nguyen TX, Huang L, Gauthier M, Yang G, Wang Q. Recent advances in liposome surface modification for oraldrug delivery. Nanomedicine (2016). 11(9), 1169–1185

71. Allen TM and Cullis PR. Liposomal drug delivery systems: from concept to clinical applications. Adv Drug Deliv Rev. 2013; 65: 36-48.

72. Riviere K, Kieler-Ferguson HM, Jerger K, Szoka FC, Jr. Anti-tumor activity of liposome encapsulated fluoroorotic acid as a single agent and in combination with liposome irinotecan. Control Release. 2011; 153: 288-296.

73. Hardiansyah, A.; Huang, L.-Y.; Yang, M.-C.; Liu, T.Y.; Tsai, S.C.; Yang, C.Y.; Kuo, C.Y.; Chan, T.Y.; Zou, H.M.; Lian, W.N.; et al. Magnetic liposomes for colorectal cancer cells therapy by high-frequencymagnetic field treatment. Nanoscale Res. Lett. 2014, 9, 497.

74. Zhou, J.; Zhao, W.-Y.; Ma, X.; Ju, R.J.; Li, X.Y.; Li, N.; Sun, M.G.; Shi, J.F.; Zhang, C.X.; Lu, W.L. The anticancer efficacy of paclitaxel liposomes modified with mitochondrial targeting conjugate inresistant lung cancer. Biomaterials 2013, 34, 3626–3638.

75. Legut, M.; Lipka, D.; Filipczak, N.; Piwoni, A.; Kozubek, A.; Gubernator, J. Anacardic acid enhances the anticancer activity of liposomal mitoxantrone towards melanoma cell lines—in vitro studies.Int. J. Nanomed. 2014, 9, 653–668.

76. Berlin Grace, V.M.; Viswanathan, S. Pharmacokinetics and therapeutic efficiency of a novel cationic liposome nano-formulated all trans retinoic acid in lung cancer mice model. J. Drug Deliv. Sci. Technol. 2017, 39, 223–236.

Received on 28.05.2020 Revised on 20.06.2020

Asian J. Pharm. Res. 2020; 10(4):293-298.

DOI: 10.5958/2231-5691.2020.00050.7