Abstract
A good balance between drug loading capacity and release was hard to achieve in matrix of transdermal drug delivery according to Higuchi theory. Herein, a controlled release drug system was conducted with -COOH polyacrylate polymer (PA-1) and an innovative mechanism was proposed to achieve the balance based on hydrogen bond and ion-ion repulsive interaction. Though thermodynamic activity of drug in PA-1 was lower than control group (without -COOH), a higher AUC of PA-1 (115.00 ± 3.96 h mg/mL) was achieved, which indicated good balance between cargo loading and drug release. As illustrated by FT-IR, Raman and molecular docking, repulsive interaction in PA-1 played a dominated role. The -COO- in PA-1 was considered as source of repulsive interaction through new peak appearance (α-carbon of COOH: 77.22 ppm) of 13C-NMR and increased carbonyl content (9%) in XPS. Moreover, repulsive interaction elevated molecular mobility with a decreased relaxation time, and enhanced electrical properties with closely to a semicircle Nyquist curve, reduced EPR line width, decreased resistivity and increased carrier mobility. In conclusion, our results revealed that ion-ion repulsion were responsible for balance between cargo loading and controlled release of NSAIDs in PA-1 and weaken hydrogen bond between drug and -COOH of PA-1.
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