Journal
NANOMATERIALS
Volume 11, Issue 11, Pages -Publisher
MDPI
DOI: 10.3390/nano11112858
Keywords
P-gP efflux; biodistribution; mucoadhesion; resistance; fluorescent micelles
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This study focuses on overcoming multidrug resistance in cancer chemotherapy by delivering paclitaxel specifically to target sites with enhanced efficacy against solid tumors. The use of multifunctional polymeric micelles for loading and releasing paclitaxel has shown significant improvements in permeation, apoptosis induction, biodistribution, and toxicity reduction. By targeting the P-glycoprotein efflux pump, the mucopermeating PT-R-Ms demonstrated a promising approach to improve cancer therapy outcomes.
P-glycoprotein (P-gP) efflux-mediated multidrug resistance is a fundamental aspect of chemotherapeutic failure in oncology. The current study aims to deliver paclitaxel (PTX) specifically at the target site with improved in vivo efficacy of poorly permeable PTX against solid tumors. Multifunctional polymeric micelles as targeted delivery have been devised for loading and release of PTX. Mucoadhesion, permeation enhancement, oral pharmacokinetics, biodistribution, and toxicological studies were carried out to fully elucidate the therapeutic outcomes of the polymeric micelles. Ex vivo permeation studies indicated a 7.89-fold enhancement in the permeation of PTX with mucopermeating papain functionalized thiolated redox micelles (PT-R-Ms) compared to the pure PTX. Moreover, PT-R-Ms exhibited a higher percentage of apoptotic cells (42.9 & PLUSMN; 0.07%) compared to pure PTX. Biodistribution studies revealed that fluorotagged PT-RMs accumulated in excised tumors and organs. The higher fluorescence intensity indicated the mucopermeation of micelles across the intestine. The orally administered PT-R-Ms efficiently overcome intestinal barriers and inhibit the P-gP efflux pump, resulting in increased bioavailability of PTX (up to 8-fold) in comparison to pure PTX. The enhanced anti-tumor efficacy and reduced toxic effects are key aspects of efficient cancer therapy. This study demonstrates that the use of mucopermeating PT-R-Ms is an encouraging approach to overwhelm the permeation barrier in cancer treatment.
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