A novel thermosensitive polymer with pH-dependent degradation for drug delivery

Abstract

A class of thermosensitive biodegradable multiblock copolymers with acid-labile acetal linkages were synthesized from Pluronic® triblock copolymers (Pluronic® P85 and P104) and di-(ethylene glycol) divinyl ether. The novel polymers were engineered to form thermogels at body temperature and degrade in acidic environment. The Pluronic®-based acid-labile polymers were characterized using nuclear magnetic resonance, gel permeation chromatography and differential scanning calorimetry. In vitro biocompatibility of the synthesized polymers was evaluated using MTT assay. The polymers showed reverse thermogelling behavior in water around body temperature. The solgel transition temperatures of the polymers synthesized from Pluronic® P85 and P104 were lowered from 70.3 to 30 o C and from 68.5 to 26.9 o C, respectively, when the synthesized polymers were compared with corresponding Pluronic® block copolymers at a concentration of 25 wt%. The hydrophobic dye solubilization confirmed the formation of polymeric micelles in the aqueous solution. The sizes of multiblock copolymer increased upon a temperature rise indicating that thermal gelation was mediated by micellar aggregation. The thermally driven hydrogels showed preferential polymer degradation at acidic pH. At pH 5.0 and 6.5, the release of 40 kDa fluorescein isothiocyanate -dextran (FITC-dextran) from the thermally formed hydrogels was completed within 2 and 9 days, respectively. However, FITC-dextran was continuously released up to 30 days at neutral pH. The mechanism of FITC-dextran release at pH 5.0 was mainly an acid-catalyzed degradation whereas both diffusion and pH-dependent degradation resulted in FITC-dextran release at pH 6.5. The novel polymers hold great potential as a pH-sensitive controlled drug delivery system due to their interesting phase transition behavior and biocompatibility.

Polymers in Small-Interfering RNA Delivery

“…These complexes displayed enhanced intracellular uptake and silencing effect of siRNA in cancer cells under applied magnetic force. Pluronic, an amphiphilic tri-block copolymer consisting of poly-(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO), is wellknown for its biocompatibility (Kwon et al, 2009;Namgung et al, 2009b;Garripelli et al, 2010). Pluronic derivatives and oleic acid-coated iron oxide nanocrystals in an organic solvent were ultrasonically emulsified in an aqueous PEI solution.…”

Synthesis and in vitro Studies of Cross-Linked Hydrogel Nanoparticles Containing Amoxicillin

“…19 Accordingly, thermo-and pH-responsive PNIPAM-based copolymers for drug delivery systems have been previously reported. [20][21][22][23][24][25] Furthermore, poly acrylic acid (PAA, Carbopol, polycarbophil) is deemed to be a polymer with bioadhesive and pH-dependence properties, even though it is difficult to maintain its effectiveness in GI tract. Using polyglycerol esters of fatty acids and PAA derivatives, mucoadhesive microparticles have been prepared and examined as in vivo and invitro in rats showing prolonged gastrointestinal residence.…”

Degradability, biocompatibility, and osteogenesis of biocomposite scaffolds containing nano magnesium phosphate and wheat protein both in vitro and in vivo for bone regeneration

“…22 It is known that the release of acidic degradation by-products from some degradable polymers could lead to inflammatory responses in vivo, and many methods have been tried to control the pH decrease during the degradation of these polymers. 23,24 In this study, it was found that there was gradually a decrease of pH in the solution containing WP (from 7.40 to 7.10), indicating that some acidic products (amino acids) might be produced from WP degradation during the soaking process. However, the pH for MWC scaffolds showed a slight increase from the initial value of 7.40 to 7.76 during the soaking process.…”