Novel methylcellulose based thermosenstive in situ nano liposomes of docetaxel for improved pharmacokinetics and pharmacodynamics with reduced toxicity

The utility of Docetaxel (DTX) in different cancers is highly compromised due to reported side effects from its commercial injectable formulation. In this work, novel methylcellulose (MC) based thermosenstive in situ nano liposomes of anti-cancer drug docetaxel (DTX) was developed for its locoregional delivery in treatment of cancer. An array of biodegradable polymers; Hydroxy propyl methyl cellulose (HPMC), Poloxamer-407 and MC for development of in situ nano liposomes (NL) were utilized alone and in combinations of one another for different sets of formulations. Optimized formulation ISNL-MC-2 exhibited in situ gelation at 36.2 ± 0.5 ºC, ideal syringeability, and sustained drug release (at 37 ± 0.5 ºC) up to 6 days with immediate in vitro gelation (5.5 ± 0.3 min). Further, a significantly higher biological half-life (23 ± 0.2 h) was detected in vivo in comparison to the commercial DTX injectable formulation (1.7 ± 0.1 h). Bio distribution study revealed almost 3 fold higher drug localization from the optimized formulation. When evaluated pharmaco dynamically in Ehrlich Ascites Carcinoma (EAC) induced mice, better tumor inhibition (87.7 ± 2.5%) was seen with the optimized formulation compared to the commercial DTX formulation (76.5 ± 2.1%). The detailed characterization and optimization brought in situ behavior of the optimized formulation close to physiological temperature using suitable concentration of MC and sodium chloride.