The effect of pH on the polymer degradation and drug release from PLGA‐mPEG microparticles

Abstract

In vitro drug release and degradation mechanism of Poly (dl-lactide-co-glycolic acid)-methoxypoly (ethyleneglycol) (PLGA-mPEG) microparticles were investigated under different pH conditions. Methotrexate(MTX), an antirheumatic drug, was employed as the model drug. In polyester-based microparticle system, two main issues involved in degradation were water uptake and the carboxylic groups produced by chain scission. Polymer composition was identified to be responsible for the odd degradation behavior in different releasing media. Because of the exposure of mPEG chains at the particle surface, microparticle degradation showed apparent different mechanism under the investigated releasing conditions. At pH 10.08, microparticles exhibited rapid weight loss but slower molecular weight decrease, and the degradation pattern was close to surface degradation. At pH 7.4, microparticles underwent heterogeneous bulk degradation. However, at pH 1.2, it showed fastest molecular weight decrease while slowest weight loss, and homogeneous degradation was observed. Particle agglomeration was also seen in acidic environment. Fourier transform infrared (FTIR) spectrum results indicated the crystallization of drugs under the low pH condition. Drug release was dependent on transport paths and drug property. These two factors were highly controlled by the polymer degradation and drug solubility in the releasing media as well as drug crystallinity.

Self‐assembled micelles prepared from poly(ɛ‐caprolactone)–poly(ethylene glycol) and poly(ɛ‐caprolactone/glycolide)–poly(ethylene glycol) block copolymers for sustained drug delivery

“…It is generally admitted that polymer degradation is affected by release conditions such as pH and temperature, which affects the drug release in turn. 37 In our work, drug release proceeded more rapidly at acidic conditions, which led to faster degradation of the hydrophobic core. The introduction of small amounts of glycolidyl moieties also slightly enhanced the release rate.…”

New insight into the mechanism of formation of dual actives loaded multilayered polymeric particles and their application in food preservation

“…The significantly faster release of both actives from System S2 compared to other system is clearly evident. This may be due to the following reasons: (1) predominant localization of benzoic acid in thick PLGA shell layer that may undergo accelerated degradation due to higher water uptake (Figure S4) by this low viscous amorphous PLGA layer leading to faster release of actives by diffusion as well as erosion controlled path . However, due to slower degradation of high viscous PLGA shell layer in System S1, the release retardation of benzoic acid was observed.…”

Synthesis, characterization, and in-vitro antitumor activity of the polyethylene glycol (350 and 1000) succinate derivatives of the tocopherol and tocotrienol isomers of Vitamin E

“…Due to their smaller size, however, isomers conjugated to mPEG 1000 had a slower hydrolysis rate. It was reported that an increase in PEG molecular weight will reduce particle size and impede the hydrolysis process (Li et al, 2008). …”