Novel Gefitinib Formulation with Improved Oral Bioavailability in Treatment of A431 Skin Carcinoma

Abstract

Purpose Oral administration of anticancer agents presents a series of advantages for patients. However, most of the anti-cancer drugs have poor water solubility leading to low bioavailability. Methods Controlled released spray dried matrix system of Gefitinib with hydroxypropyl β-cyclodextrin, chitosan, hydroxy propyl methyl cellulose, vitamin E TPGS, succinic acid were used for the design of formulations to improve the oral absorption of Gefitinib. Spray drying with a customized spray gun which allows simultaneous/pulsatile flow of two different liquid systems through single nozzle was used to prepare Gefitinib spray dried formulations (Gef-SD). Formulation was characterized by in vitro drug release and Caco-2 permeability studies. Pharmacokinetic studies were performed in Sprague Dawley rats. Efficacy of Gef-SD was carried out in A431 xenografts models in nude mice. Results In Gef-SD group 9.14-fold increase in the AUC was observed compared to free Gef. Improved pharmacokinetic profile of Gef-SD translated into increase (1.75 fold compared to Gef free drug) in anticancer effects. Animal survival was significantly increased in Gef formulation treated groups, with superior reduction in the tumor size (1.48-fold) and volumes (1.75-fold) and also increase in the anticancer effects (TUNEL positive apoptotic cells) was observed in Gef-SD treated groups. Further, western blot, immunohistochemical and proteomics analysis demonstrated the increased pharmacodynamic effects of Gef-SD formulations in A431 xenograft tumor models. Conclusion Our studies suggested that Gefitinib can be successfully incorporated into control release microparticles based oral formulation with enhanced pharmacokinetic and pharmacodynamic activity. This study demonstrates the novel application of Gef in A431 tumor models.

Novel diindolylmethane derivatives based NLC formulations to improve the oral bioavailability and anticancer effects in triple negative breast cancer

“…Significant reduction in the VEGF levels was observed in tumor lysates in C-DIM treated groups. The role of VEGF in angiogenesis is very well documented in several studies and antiangiogenic effects of C-DIM were also reported in previous studies, which are in agreement with our present findings [2,7]. Our NLC based oral formulation approach may provide superior anticancer drug delivery strategies for poorly water soluble drugs to improve the pharmacokinetics problems associated with several interesting anticancer agents.…”

Honokiol nanomicellar formulation produced increased oral bioavailability and anticancer effects in triple negative breast cancer (TNBC)

“…The colonies/spheroids grown in each well were fixed in glutaraldehyde and stained with crystal violet. Number of colonies was counted with an optical microscope and colony sizes were measured and representative spheroid images were captured [25]. …”

Improved Dissolution and Pharmacokinetics of Abiraterone through KinetiSol® Enabled Amorphous Solid Dispersions

“…ASDs have been reported to enhance the pharmacokinetics of several anticancer drugs [24][25][26]. Also, ASDs have been reported to improve the therapeutic outcomes of anti-cancer drugs such as vemurafenib and gefitinib [26][27][28]. Hence, ASDs represent a promising formulation to enhance the dissolution of abiraterone and improve its pharmacokinetic properties, once a suitable manufacturing technique is found.…”