A thermo-sensitive PLGA-PEG-PLGA hydrogel for sustained release of docetaxel

Abstract

The aim of this study was to investigate the suitability of poly-(d,l-lactic acid-co-glycolic acid) (PLGA)-polyethylene glycol (PEG)-PLGA triblock copolymer as a matrix material for a sustained-release system for docetaxel (DTX). The copolymers were synthesized by ring-opening polymerization reaction and characterized by (1)H-NMR and gel permeation chromatography. The DTX-loaded formulations were prepared, characterized. And the antitumor efficacy and the pharmacokinetics of DTX-loaded copolymer on A-549 lung tumor-bearing BALB/cA mice were investigated. The results showed that DTX-loaded copolymer highly increased the solubility of DTX by more than 3000-fold. And copolymer concentration as well as drug loading level exerted appreciable influence on the drug release behavior. Further, the pharmacokinetic test showed that DTX-loaded copolymer could be with the sustained-release nature for over 3 weeks, which correlated well with the in vitro release. Additionally, one intratumoral injection of the thermo-sensitive hydrogel containing DTX was comparable to three intravenous injections of DTX injection in inhibiting the tumor growth in A-549 lung tumor-bearing BALB/cA mice with a less toxic manner. PLGA-PEG-PLGA could thus provide a promising alternate locally delivered vehicle for DTX to achieve prolonged exposure having greater efficacy in inhibiting tumor growth with lower toxicity.

A PLGA–PEG–PLGA Thermosensitive Gel Enabling Sustained Delivery of Ropivacaine Hydrochloride for Postoperative Pain Relief

“…This result is consistent with many previous studies. 23,25) The in vitro release profile was consistent with the Higuchi equation (Q=0.1026t 1/2 +0.0141, r 2 =0.9994). RP was primarily released from the PLGA-PEG-PLGA gel through diffusion.…”

“…Notably, we observed that the gelation temperature increased at higher RP concentrations, which is a different result from those found in previous reports of drug-loaded PLGA-PEG-PLGA gels. 21,[23][24][25] This discrepancy might be related to the interaction between the drug and the polymer. Some researchers have assumed that the hydrophilic or soluble salts of drug molecules, after absorbing water molecules themselves, can reduce the water activity and access of PEG blocks to the water molecules, thereby facilitating the phase transition at lower temperatures.…”

Efficacy, Pharmacokinetics, and Biodistribution of Thermosensitive Chitosan/β-Glycerophosphate Hydrogel Loaded with Docetaxel

“…After 21 days, the total release of the 1 mg/mL loaded gel was 92.85% while the one of the 4 mg/mL loaded gel was only 76.68%. The increase of viscoelasticity might contribute to the different release characteristics (14). For gelling system, the drug release patterns may be affected by interactions between drug and gel such as hydrophobic or hydrogen bonding interactions (33).…”

“…Several hydrogels for localized delivery of DTX have been reported such as pluronic F127-based reversal thermal gels (13) and poly-(D,L-lactic acid-co-glycolic acid) (PLGA)-polyethylene glycol (PEG)-PLGA hydrogel (14). Nevertheless, the application of pluronic in drug delivery system is restricted, partly ascribed to its high toxicity and nonbiodegradability (15).…”

Nanotechnology-based drug delivery systems for treatment of oral cancer: a review

“…There has been a great deal of interest in the use of hydrogels as chemotherapeutic drug delivery systems for drugs including paclitaxel, doxorubicin, DTX, tamoxifen, and cisplatin. [162][163][164][165][166][167][168][169][170][171] Furthermore, studies have revealed that strategies are required to overcome the disadvantages of chemotherapeutic drugs such as cisplatin, which is usually intravenously administered, whereby 90% becomes linked to hemoproteins and 10% is free to enter into the cells.…”