BITS Faculty Publications
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Item Exploring temozolomide encapsulated PEGylated liposomes and lyotropic liquid crystals for effective treatment of glioblastoma: in-vitro, cell line, and pharmacokinetic studies(Elsevier, 2023-05) Singhvi, Gautam; Roy, AniruddhaTemozolomide (TMZ) is one of the best choices for treating glioblastoma. However, due to the short plasma half-life, only 20–30 % brain bioavailability can be achieved using traditional formulations. In the present study, PEGylated liposomes and lyotropic liquid crystals (LLCs) were developed and investigated to prolong the plasma circulation time of TMZ. Industrially feasible membrane extrusion and modified hot melt emulsification techniques were utilized during the formulation. Liposomes and LLCs in the particle size range of 80–120 nm were obtained with up to 50 % entrapment efficiency. The nanocarriers were found to show a prolonged release of up to 72 h. The cytotoxicity studies in glioblastoma cell lines revealed a ∼1.6-fold increased cytotoxicity compared to free TMZ. PEGylated liposomes and PEGylated LLCs were found to show a 3.47 and 3.18-fold less cell uptake in macrophage cell lines than uncoated liposomes and LLCs, respectively. A 1.25 and 2-fold increase in the plasma t1/2 was observed with PEGylated liposomes and PEGylated LLCs, respectively, compared to the TMZ when administered intravenously. Extending plasma circulation time of TMZ led to significant increase in brain bioavailability. Overall, the observed improved pharmacokinetics and biodistribution of TMZ revealed the potential of these PEGylated nanocarriers in the efficient treatment of glioblastoma.Item Quality by design assisted optimization of temozolomide loaded PEGylated lyotropic liquid crystals: Investigating various formulation and process variables along with in-vitro characterization(Elsevier, 2022-04) Singhvi, Gautam; Roy, AniruddhaTemozolomide (TMZ) is approved for the treatment of glioblastoma. The objective of the present study was to develop and characterize TMZ loaded lyotropic liquid crystals (LLCs) for intravenous delivery. Various formulation and process variables were studied in detail, following the quality by design principles. A three-level Box Behnken design was used for optimization. The effect of lipid concentration, surfactant concentration, and co-surfactant concentration on response variables like size, size distribution, zeta potential, entrapment efficiency, and drug loading was investigated using the statistical data obtained by Design Expert® software. The results demonstrated that LLCs were obtained in the size range of 53.15–186.50 nm with PDI less than 0.25. The optimized formulation showed particle size of 97.70 ± 0.481 nm and entrapment efficiency of 36.46 ± 1.48%. TMZ loaded LLCs were found to follow Korsmeyer's Peppas model and showed sustained release up to 72 h. The LLCs were further PEGylated to prevent hemolysis and achieve long plasma circulation. PEGylated LLCs showed less than 5% hemolysis. TMZ loaded LLCs demonstrated higher cytotoxicity towards glioma cell lines as compared to native TMZ. The results revealed that the prepared LLCs could be a potential delivery system to enhance the efficacy of TMZ. Additionally, the preparation method involved a minimum number of steps ensuring reproducibility and scalability.