Novel amphiphilic folic acid-cholesterol-chitosan micelles for paclitaxel delivery

Abstract

In order to decrease the toxicity of paclitaxel (PTX) and increase the efficiency, we developed an amphiphilic PTX injection system using a biodegradable and biocompatible polymer synthesized by folic acid, cholesterol, and chitosan (FACC). This FACC-based polymer had a low critical concentration (64.13μg/ml) and could self-assemble in aqueous condition to form nanoscale micelles. The particle sizes of FACC-PTX micelles were 253.2±0.56 nm, the encapsulation efficiency and loading capacity of these FACC-PTX micelles were 65.1±0.23% and 9.1±0.16%, respectively. The cumulative release rate was about 85% at pH 5.0 which was higher than that at pH 7.4 (76%). This pH-dependent release behavior was highly suggesting that PTX release from FACC-PTX micelles might be higher in a weak acidic tumor microenvironment and lower toxic for normal cells. The anti-cancer effectiveness of FACC-PTX micelles was investigated by in vitro cytotoxicity and targeting study. The results revealed that FACC micelles have non-toxic on cells as evidenced by high cell viability found (86% to 100%) in the cells cultured with various concentrations of FACC micelles (1 to 500 μg/ml). Targeting study indicated that the cytotoxic efficacy of FACC-PTX micelles was significantly higher than that with Taxol® in the Hela cells (folate receptor-positive cells). These findings indicated that the anticancer efficiency of PTX can be enhanced by adding some cancer cell positive receptor into drug carrier and the FACC micelle was a potential tumor targeting carrier for PXT delivery.

Amphiphilic Polymeric Micelles Based on Deoxycholic Acid and Folic Acid Modified Chitosan for the Delivery of Paclitaxel

“…Moreover, the abundant active amine and hydroxyl groups in CS could offer many opportunities for chemical modification. In recent years, several chitosan-based PTX delivery systems have been developed, such as N -mercapto acetyl- N ′-octyl- O , N ′′-glycol chitosan micelles [ 13 ], 3,6- O , O ′-dimyristoyl chitosan micelles [ 14 ], folic acid–cholesterol–chitosan micelles [ 15 ], PTX conjugated trimethyl chitosan nanoparticles [ 16 ], palmitoyl chitosan nanoparticles [ 17 ], N -succinyl-chitosan nanoparticles [ 18 ] and PTX-loaded chitosan nanoparticles prepared by the nano-emulsion method [ 19 ]. However, chitosan with high molecular weight has poor solubility in aqueous medium at neutral pH, which limits its medical and pharmaceutical applications.…”

Indomethacin-based stimuli-responsive micelles combined with paclitaxel to overcome multidrug resistance

“…The encapsulation efficiency (EE%) and drug loading (DL%) were determined as described previously [ 26 ]. Briefly, 0.5 mL DEX-SS-IND/PTX micelle solution was dissolved in 9.5 mL DMSO to dissolve all PTX.…”

Targeted Chemotherapy via Folic Acid Decorated Nanomedicines

“…Folic acid conjugated nanomedicines has also reported to increase the efficacy of paclitaxel and cisplatin in cervix cancer cells facilitating the intracellular uptake. In vitro studies in Hela cells (FR-α positive) have demonstrated that paclitaxel micelles [12] and gelatin nanoparticles loaded with cisplatin [13] and decorated with folic acid improve the inhibition of cell proliferation, increasing therapeutic efficacy. This inhibition improvement of folate decorated micelles of PTX was not observed in A459 lung adenocarcinoma cells (FR-α negative), showing a similar efficacy than non-targeted formulations and indicating that folic acid conjugation is the responsible of the enhancement of anticancer efficacy [13] (Table1).…”