Shaılesh SHARMA, Neelam SHARMA, Surajpal VERMA, Deepak BHAGWAT

Development of liposomal topical gel of bexarotene for effective management of cutaneous t-cell lymphoma: Formulation to preclinical assessment

Background and Aims: The objective of this work was to formulate liposomal gel formulation of bexarotene for Cutaneous T-cell Lymphoma (CTCL). Low solubility and high log P value make the drug a poor candidate for its penetrability and absorp- tion through the transdermal route. When bexarotene is incorporated into liposomal formulation, its solubility and perme- ability can enhance. Methods: In the present investigation, the liposomes of bexarotene were prepared by thin film-hydration method and opti- mized for different critical processing parameters such as the amount of lipid and the time of stirring. Checkpoint batches were prepared to validate the mathematical model. Results: The final optimized liposome formulation, which has more than 85% entrapment efficiency and vesicle size of 625 nm, was prepared. The optimized liposomes were loaded (equivalent to 1% w/w bexarotene) into the carbopol gel (1.5% w/w) and, evaluated for physico-chemical parameters. In vitro drug permeation and deposition of promised liposomal gel were performed through rat skin. The skin irritation studies of the liposomal gel were examined on rats, in vivo. MTT assay was performed to determine the cytotoxicity and cell apoptosis on CTCL specified cell line (Hut-78) by bexarotene liposomal gel. The optimized liposomes of bexarotene (FL1) were found to be spherical having a vesicle size of 639 nm with PDI 0.115 and a zeta potential value of -19.3 mV. The promised liposomal gel (LG5) evaluations were found in the limit. The LG5 was shown 31% bexarotene deposition in the skin. The experiment revealed a significant decrease (p<0.005) in the number of viable cells following MTT assay. Conclusion: The liposomal gel formulation of bexarotene improved the treatment and management of CTCL.

Keywords:

Bexarotene, Liposome Topical Gel, Lymphoma, MTT assay, UV skin irritation studies,

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