Redox-sensitive micelles for targeted intracellular delivery and combination chemotherapy of paclitaxel and all-trans-retinoid acid

Publication date: Available online 24 September 2018Source: Asian Journal of Pharmaceutical SciencesAuthor(s): Lingfei Han, Lejian Hu, Fulei Liu, Xin Wang, Xiaoxian Huang, Bowen Liu, Feng Feng, Wenyuan Liu, Wei QuAbstractThe application of paclitaxel (PTX) in clinic has been restricted due to its poor solubility. Several traditional nano-medicines have been developed to improve this defect, while they are still lack of tumor targeting ability and rapid drug release. In this work, an amphiphilic polymeric micelle of hyaluronic acid (HA) - all-trans-retinoid acid (ATRA) with a disulfide bond, was developed successfully for the co-delivery of PTX and ATRA. The combination chemotherapy of PTX and ATRA can strengthen the anti-tumor activity. Along with self-assembling to micelles in water, the delivery system displayed satisfying drug loading capacities for both PTX (32.62% ± 1.39%) and ATRA, due to directly using ATRA as the hydrophobic group. Rapid drug release properties of the PTX-loaded redox-sensitive micelles (HA-SS-ATRA) in vitro were confirmed under reducing condition containing GSH. Besides, HA-CD44 mediated endocytosis promoted the uptake of HA-SS-ATRA micelles by B16F10 cells. Due to these properties, cytotoxicity assay verified that PTX-loaded HA-SS-ATRA micelles showed concentration-dependent cytotoxicity and displayed obvious combination therapy of PTX and ATRA. Importantly, HA-SS-ATRA micelles could remarkably prolong plasma circulation time after intravenously ad...
Source: Asian Journal of Pharmaceutical Sciences - Category: Drugs & Pharmacology Source Type: research