β-Cyclodextrin-based (IA-co-AMPS) Semi-IPNs as smart biomaterials for oral delivery of hydrophilic drugs: Synthesis, characterization, in-Vitro and in-Vivo evaluation

Currently, the synthesis of multi-polymer based hydrogels called interpenetrating networks (IPNs) is more in practice due to enhanced tunability and effective drug release features in comparison to single components. IPNs are synthesized by crosslinking two or more polymeric networks where one of the networks is synthesized in the presence of the other network. In comparison to conventional hydrogels, the IPN systems exhibit enhanced mechanical features with good swelling, drug entrapment and release profile. The objective of this study was to prepare beta-CD-based pH-responsive semi-IPN hydrogels utilizing the strong ionizable functionalities of itaconic acid (IA) and 2 acrylamido-2methylpropane sulfonic acids AMPS. The semi-IPNs were prepared through free radical polymerization technique using N, N'-methylene bisacrylamide (MBA) as a crosslinking agent and ammonium persulfate (APS) as reaction imitator. Loxoprofen sodium was chosen as a model drug. The network formation and drug loading were confirmed through Fourier transform infrared spectroscopy (FTIR) while thermal behavior was evaluated through thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). X-ray diffraction (XRD) and scanning electron microscopy (SEM) were used to check the change in the crystallinity and morphology of the prepared semi-IPNs. The behavior, efficiency, safety and oral tolerability of the semi-IPNs were tested through various in-vitro and in-vivo studies. FTIR results confirmed the successful crosslinking and drug loading in the semi-IPNs while TGA and DSC proved their thermal stability. XRD showed a decrease in crystallinity while SEM confirmed the uneven and rough surface with some cracks. The semi-IPNs exhibited high swelling and drug release at pH 5.5 and 7.4 than the acidic pH 1.2. Drug release followed first-order kinetic while release phenomena was diffusion-based following non-Fickian mechanism. Oral tolerability suggested that the hydrogel dispersion was well tolerable up to 3200 mg/kg without causing any histopathological or hematological changes. The obtained results suggested that beta-CD-IA-AMPS semi-IPNs could be a safe and efficient carrier for oral delivery of hydrophilic drugs.