Formulation Development, Characterization and In-vitro Evaluation of Tamoxifen Loaded Liposomes

Main Article Content

Md. Mazed Hasan
Md. Hamiduzzaman
Ishrat Jahan
A. H. M. Nazmul Hasan
Md. Asaduzzaman


Background: The study was aimed to prepare and evaluate tamoxifen loaded controlled release liposomes to reduce the side effects of tamoxifen during cancer treatment. 

Methods: Different tamoxifen loaded liposomes were prepared by modified ether injection (MEIM) and thin film hydration method (TFHM) under prescribed conditions. The prepared liposomes were characterized by using optical microscopy, evaluating encapsulation efficiency, in-vitro and ex-vivo diffusion studies by using dialysis membrane and chicken intestinal sac respectively.

Results: The data revealed that all of the liposomes were spherical in shape and stable under three physical conditions i.e. 4, 25 and 37 ± 2°C temperatures and 60 ±5% relative humidity. Additionally most of the liposomes followed zero order and class II release kinetics. It was also observed that with the increase of phospholipids and cholesterol, entrapment efficiency of liposome vesicles increased thus giving a controlled release drug delivery system but further increase reduced this efficiency at a certain level.

Conclusion: The formulated control release liposomes might be a good drug delivery system for target oriented drug delivery with minimum side effects of tamoxifen during cancer treatment.

Tamoxifen, liposomes, ether injection method, thin film hydration method, controlled release, in-vitro drug diffusion study.

Article Details

How to Cite
Hasan, M. M., Hamiduzzaman, M., Jahan, I., Hasan, A. H. M. N., & Asaduzzaman, M. (2020). Formulation Development, Characterization and In-vitro Evaluation of Tamoxifen Loaded Liposomes. Journal of Pharmaceutical Research International, 32(6), 64-82.
Original Research Article


Shagufta, Ahmad I. Tamoxifen a pioneering drug: An update on the therapeutic potential of tamoxifen derivatives. European Journal of Medicinal Chemistry. 2018;1(143):515-531.

Kastrati I, Joosten SEP, Semina SE, Alejo LH, Brovkovych SD, Stender JD, et al. The NFκB pathway promotes tamoxifen tolerance and disease recurrence in estrogen receptor positive breast cancers. Molecular Cancer Research. 2020;1082: 2019. .

Bhattacharyya GS. Oral systemic therapy: Not all win-win. Indian Journal of Medical Paediatric Oncology. 2010;31(1):1–3.

Whitfield J, Littlewood T, Soucek L. Tamoxifen administration to mice.Cold Spring Harbor Protocols. 2015;2015(3): 269-71.

Bozzuto G, Molinari A. Liposomes as nano-medical devices. International Journal of Nanomedicine. 2015;10:975–999.

Bangham AD, Horne RW. Negative staining of phospholipids and their structural modification by surface-active agents as observed in the electron microscope. Journal of Molecular Biology. 1964;8:660–668.

Felice B, Prabhakaran MP, Rodríguez AP, Ramakrishna S. Drug delivery vehicles on a nano-engineering perspective. Journal of Material Science Engineering. 2014;41: 178–195.

Budai L, Hajdú M, Budai M, Gróf P, Béni S, Noszál B, et al. Gels and liposomes in optimized ocular drug delivery: Studies on ciprofloxacin formulations. International Journal of Pharmaceutics. 2007;343:34–40.

Vyas SP, Rawat M, Rawat A, Mahor S, Gupta PN. Pegylated protein encapsulated multivesicular liposomes: A novel approach for sustained release of Interferon α. Drug Development and Industrial Pharmacy. 2006;32:699–707.

Anabousi S, Laue M, Lehr CM, Bakowsky U, Ehrhardt C. Assessing transferrin modification of liposomes by atomic force microscopy and transmission electron microscopy. European Journal of Pharmacy and Biopharmaceutics. 2005; 60:295–303.

Abraham SA, Waterhouse DN, Mayer LD, Cullis PR, Madden TD, Bally MB. The liposomal formulation of doxorubicin. Methods Enzymology. 2005;391:71–97.

Vyas SP, Quraishi S, Gupta S, Jaganathan KS. Aerosolized liposome-based delivery of amphotericin B to alveolar macrophages. International Journal of Pharmaceutics. 2005;296:2–25.

Devaraj GN, Parakh SR, Devraj R, Apte SS, Rao BR, Rambhau D. Release studies on niosomes containing fatty alcohols as bilayer stabilizers instead of cholesterol. Journal of Colloid Interface Science. 2002; 251(2):360-5.

Alexopoulou E, Georgopoulos A, Konstantinos A. Kagkadis, Demetzos C. Preparation and characterization of lyophilized liposomes with incorporated quercetin. Journal of Liposome Research. 2006;16(1):17-25.

Laouini A, Jaafar-Maalej C, Limayem-Blouza I, Sfar S, Charcosset C, Fessi H. Preparation, characterization and applications of liposomes: State of the art. Journal of Colloid Science. 2012;1:147–168.

Huang Z, Li X, Zhang T, Song Y, She Z, Li J et al. Asian Journal of Pharmaceutical Sciences. 2014;9(4):176-182.

Wagener K, Worm M, Pektor S, Schinnerer M, Thiermann R, Miederer M, et al. Comparison of linear and hyperbranched polyether lipids for liposome shielding by 18F-radiolabeling and positron emission tomography. Biomacromolecules. 2018; 19(7):2506 2516.

Zhang H. Thin-film hydration followed by extrusion method for liposome preparation. Methods Molecular Biology. 2017;1522:17-22.

Yang S. Preparation, in vitro characterization and pharmacokinetic study of coenzyme q10 long-circulating liposomes. Drug Research. 2018;68(5): 270-279.

Yadav AV, Murthy MS, Shete AS, Sakhare S. Stability aspects of liposomes. Indian Journal of Pharmaceutical Education and Research. 2011;45(4):402-413.

Akashi K, Miyata H, Itoh H, Kinosita K. Preparation of giant liposomes in physiological conditions and their characterization under an optical microscope. Biophysical Journal. 1996; 71(6):3242-3250.

Buchanan CM, Buchanan NL, Edgar KJ, Lambert JL, Posey‐Dowty JD, Ramsey MG et al. Solubilization and dissolution of tamoxifen‐hydroxybutenylcyclodextrin complexes. Journal of Pharmaceutical Science. 2006;95(10):2246-2255.

Mura P, Maestrelli F, Rodríguez MLG, MichelacciI, Ghelardini C, Rabasco AM. Development, characterization and in vivo evaluation of benzocaine-loaded liposomes. European Journal of Pharmaceutics and Biopharmaceutics. 2007;67(1):86-95.

Zhang L, Alfano J, Race D, Davé RN. Zero-order release of poorly water-soluble drug from polymeric films made via aqueous slurry casting. European Journal of Pharmaceutical Science. 2018;117:245-254.

Madni A, Rahim MA, Mahmood MA, Jabar A, Rehman M, Shah H, et al. Enhancement of dissolution and skin permeability of pentazocine by proniosomes and niosomal gel.AAPS Pharmaceutical Science and Technology. 2018;19(4):1544-1553.

Wójcik-Pastuszka D, Krzak J, Macikowski B, Berkowski R, Osiński B, Musiał W. Evaluation of the release kinetics of a pharmacologically active substance from model intra-articular implants replacing the cruciate ligaments of the knee. Materials. 2019;12(8):1202.

Simionato LD, Petrone L, Baldut M, Bonafede SL, Segall AI. Comparison between the dissolution profiles of nine meloxicam tablet brands commercially available in Buenos Aires, Argentina. Saudi Pharmaceutical Journal. 2018;26(4): 578–584.

Cascone S. Modeling and comparison of release profiles: Effect of the dissolution method. European Journal of Pharmaceutical Science. 2017;106:352-361.

Choonara BF, Choonara YE, Kumar P, Toit LC, Tomar LK, Tyagi C, et al. A menthol-based solid dispersion technique for enhanced solubility and dissolution of sulfamethoxazole from an oral tablet matrix. Technology. 2015;16(4):771–786.

Amiri S, Rezazadeh-Bari M, Alizadeh-Khaledabad M, Amiri S. New formulation of vitamin C encapsulation by nanoliposomes: Production and evaluation of particle size, stability and control release. Food Science Biotechnology. 2019;28(2):423–432.

Briuglia ML, Rotella C, McFarlane A, Lamprou DA. Influence of cholesterol on liposome stability and on in vitro drug release. Drug Delivery and Translational Research. 2015;5(3):2015.

Li J, Wang X, Zhang T, Wang C, Huang Z, Luo X, et al. A review on phospholipids and their mainapplications in drug delivery systems. Asian Journal of Pharmaceutical Sciences. 2015;81-98.

Shaker S, Gardouh AR, Ghorab MM. Factors affecting liposomes particle size prepared by ethanol injection method. Research in Pharmaceutical Science. 2017;12(5):346–352.

Jacops E, Aertsens M, Maes N, Bruggeman C, Swennen R, Krooss B, et al. The dependency of diffusion coefficients and geometric factoronthe size of the diffusing molecule: Observations for different clay-based materials. Hindawi. 2017;1-16.

Fu Y, Kao WJ. Drug release kinetics and transport mechanisms of non-degradable and degradable polymeric delivery systems. Expert Opinion Drug Delivery. 2010;7(4):429–444.

Shazly GA. Propranolol liposomes: Formulation, characterization, and in vitro release. Journal of Optoelectronic Biomedical Mater. 2013;5(1):17-25.

Bhatia A, Kumar R, Katare OP. Tamoxifen in topical liposomes: Development, characterization and in vitro evaluation. Journal of Pharmacy and Pharmaceutical Sciences. 2004;7(2):252-259.

Chanda H, Das P. Development and evaluation of liposomes of fluconazole. Journal of Pharmaceutical and Biomedical Sciences. 2011;5(27):1-9.

Ghanbarzadeh S, Valizadeh H, Milani PZ. Application of response surface methodology in development of sirolimus liposomes prepared by thin film hydration technique. BioImpacts. 2013; 3(2):75-81.

Kumar A, Badde S, Kamble R, Pokharkar VB. Development and characterization of liposomal drug delivery system for nimesulide. International Journal of Pharmacy and Pharmaceutical Sciences. 2010;2(4):87-89.

Nitesh JV, Ranjan MM. Comparative physical and chemical stability studies of orlistat liposomal drug delivery systems. Asian Journal of Pharmaceutics. 2018;12 (3):972.

Khan R, Ashraf MS, Afzal M, Kazmi I, Jahangir MA, Singh R, et al. Formulation and evaluation of sustained release matrix tablet of rabeprazole using wet granulation technique. Journal of Pharmaceutical Bioallied Science. 2014; 6(3):180–184.