Amol A. Tatode, Arun T. Patil, Milind J. Umekar


Objective: The present investigation was aimed to optimize the formula of paclitaxel-loaded   liposomes (PTL) by using the application of response surface methodology (RSM).

Method: Paclitaxel-loaded liposome (PTL) was optimized by response surface methodology based on two parameters, namely, percent entrapment efficiency (% EE) and percent in vitro drug release at 12 hrs (% DR). The liposome formula was prepared using 32 factorial design, and the selected independent variables were, phospholipid (phospholipon 90G) and cholesterol (CH) concentrations. Nine formulas of paclitaxel-loaded liposome were prepared by thin film hydration technique (THF). The entrapment efficiency, in vitro release studies and drug content, were evaluated using on UV -visible spectrophotometer at λmax- 230 nm. The developed PTL formulation vesicle morphology, particle size, polydispersity index (PDI) and zeta potential (ζ) were evaluated by Motic digital microscope and Malvern zetasizer respectively.

Result: Using response surface methodology the estimated coefficient values obtained for independent variables in the regression equations, exhibited that the phospholipid (PL90G) and cholesterol (CH) molar concentration was observed to be highly influencing variables in optimizing % EE (86.67 ± 0.67) and % DR (63.49 ± 1.21). In the prediction of % EE and % DR values, the percent relative errors (PRE) was found to be low (–0.290%) and (0.058%) respectively. This suggests that design-developed model was found to be suitable for PTL formulations and thus, validate the model. 

Conclusion: Experimental results show that the observed responses were in close agreement with the predicted values and this demonstrates the reliability of the RSM in an optimization of % EE and % DR in paclitaxel liposomal (PTL) formulations.


Liposomes, Phospholipon, Paclitaxel, Response surface methodology, 32 factorial design, Thin film hydration technique.


Louage B, De Wever O, Hennink WE, De Geest BG. Developments and future clinical outlook of taxane nanomedicines. J Control Rel 2017;253:137-52.

Ye J, Liu Y, Xia X, Meng L, Dong W, Wang R, et al. Improved safety and efficacy of a lipid emulsion loaded with a paclitaxel-cholesterol complex for the treatment of breast tumors. Oncol Rep 2016;36:399-409.

Kampan NC, Madondo MT, McNally OM, Quinn M, Plebanski M. Paclitaxel and its evolving role in the management of ovarian cancer. BioMed Res Int 2015;2015:1-21.

Wang L, Yu RS, Yang WL, Luan SJ, Qin BK, Pang XB, et al. Effects of paclitaxel loaded-drug micelles on cell proliferation and apoptosis of human lung cancer A549 cells. Acta pharmaceutica sinica 2015;50:1240-5.

Lemstrova R, Melichar B, Mohelnikova-Duchonova B. Therapeutic potential of taxanes in the treatment of metastatic pancreatic cancer. Cancer Chemother Pharmacol 2016;78:1101-11.

Webster LK, Woodcock DM, Rischin D and Millward MJ. Review: Cremophor: pharmacological activity of an" inert" solubiliser. J Oncol Pharm Pract 1997;3:186-92.

Cragun JM, Baggs JH, Rollins C, Chambers SK. Case Report Hypersensitivity reaction to parenteral nutrition after severe hypersensitivity reaction to paclitaxel. Am J Clin Exp Obstet Gynecol 2013;1:69-75.

Singla AK, Garg A and Aggarwal D. Paclitaxel and its formulations. Int J Pharm 2002;235:179-92.

Moes J, Koolen S, Huitema A, Schellens J, Beijnen J, Nuijen B. Development of an oral solid dispersion formulation for use in low-dose metronomic chemotherapy of paclitaxel. Eur J Pharm Biopharm 2013;83:87-94.

Sandhu PS, Beg S, Mehta F, Singh B, Trivedi P. Novel dietary lipid-based self-nanoemulsifying drug delivery systems of paclitaxel with p-gp inhibitor: implications on cytotoxicity and biopharmaceutical performance. Expert Opin Drug Deliv 2015;12:1809-22.

Li J, Wang F, Sun D, Wang R. A review of the ligands and related targeting strategies for active targeting of paclitaxel to tumours. J Drug Target 2016;24:590-602.

Xu J, Zhang X, Chen Y, Huang Y, Wang P, Wei Y, et al. Improved micellar formulation for enhanced delivery for paclitaxel. Mol Pharm 2016;14:31-41.

Bonde S, Nair S. Advances in liposomal drug delivery system: fascinating types and potential applications. Int J App Pharm 2017;9:1-7

Li J, Huang P, Chang L, Long X, Dong A, Liu J, et al. Tumor targeting and pH-responsive polyelectrolyte complex nanoparticles based on hyaluronic acid-paclitaxel conjugates and chitosan for oral delivery of paclitaxel. Macromol Res 2013;21:1331-7.

Teow HM, Zhou Z, Najlah M, Yusof SR, Abbott NJ, D’Emanuele A. Delivery of paclitaxel across cellular barriers using a dendrimer-based nanocarrier. Int J Pharm 2013;441:701-11.

Al-Najjar BY, Hussain SA. Chitosan microspheres for the delivery of chemotherapeutic agents: paclitaxel as a model. Asian J Pharm Clin Res. 2017;10:1-5.

Kulkarni PR, Yadav JD, Vaidya KA. Liposomes: a novel drug delivery system. Int J Curr Pharm Res. 2011;3:10-8.

Zhang W, Wang G, Falconer JR, Baguley BC, Shaw JP, Liu J, et al. Strategies to maximize liposomal drug loading for a poorly water-soluble anticancer drug. Pharm Res 2015;32:1451-61.

Zhang H, Gong W, Wang ZY, Yuan SJ, Xie XY, Yang YF, et al. Preparation, characterization, and pharmacodynamics of thermosensitive liposomes containing docetaxel. J Pharm Sci 2014;103:2177-83.

Bhatia A, Singh B, Raza K, Shukla A, Amarji B and Katare OP. Tamoxifen-loaded novel liposomal formulations: evaluation of anticancer activity on DMBA-TPA induced mouse skin carcinogenesis. J Drug Target 2012;20:544-50.

Carbone C, Tomasello B, Ruozi B, Renis M, Puglisi G. Preparation and optimization of PIT solid lipid nanoparticles via statistical factorial design. Eur J Med Chem 2010;49:110-7.

Hermans K, Van den Plas D, Everaert A, Weyenberg W, Ludwig A. Full factorial design, physicochemical characterisation and biological assessment of cyclosporine A loaded cationic nanoparticles. Eur J of Pharm Biopharm 2012;82:27-35.

Krishnaiah D, Bono A, Sarbatly R, Nithyanandam R, Anisuzzaman SM. Optimisation of spray drying operating conditions of Morinda citrifolia L. Fruit extract using response surface methodology. J King Saud Univ 2012;27:26-36.

Minitab. What is a Response Surface Design? 2016. Available from: modeling-statistics/doe/response-surface-designs/what-is-a-response-surface-design.

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

Sudhakar B, Krishna MC, Murthy KV. Factorial design studies of antiretroviral drug-loaded stealth liposomal injectable: PEGylation, lyophilization and pharmacokinetic studies. Appl Nanosci 2016;6:43-60.

Dua JS, Rana AC, Bhandari AK. Liposome: methods of preparation and applications. Int J Pharm Stud Res 2012;3:14-20.

Yang T, Cui FD, Choi MK, Lin H, Chung SJ, Shim CK, et al. Liposome formulation of paclitaxel with enhanced solubility and stability. Drug Deliv 2007;14:301-8.

Utreja P, Jain S and Tiwary AK. Localized delivery of paclitaxel using elastic liposomes: Formulation development and evaluation. Drug Deliv 2011;18:367-76.

Damai RS, Silvia S and Etik M. Optimization of luteolin-loaded transfersome using response surface methodology. Int J App Pharm 2017;9(Special Issue-oct):107-11.

Majumdar S, Debnath R, Bhattacharjee A, Banerjee A, Patro CS. Statistical optimization and characterization of prepared Fluconazole topical liposomal gel for improved skin permeation. Pelagia Res Lib 2014;5:42-55.

Tatode AA, Patil AT, Umekar MJ, Telange DR. Investigation of effect of phospholipids on physical and functional characterization of paclitaxel liposomes. Int J Pharm Pharm Sci 2017;9:141-6.

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