Synthesis, optimization, and evaluation of polyvinyl alcohol‐based hydrogels as controlled combinatorial drug delivery system for colon cancer

Abstract

The purpose of current research work was to synthesize and evaluate the cross‐linked ternary hydrogels using polyvinyl alcohol (PVA) and two monomers itaconic acid and methacrylic acid. Controlled combinatorial drug delivery systems (CCDDS) were synthesized by free radical solution polymerization method using ethylene glycol dimethacrylate (EGDMA) as cross‐linking agent. 5‐Fluorouracil (5‐FU) and leucovorin calcium (LC) were loaded in combination into synthesized gels for colonic delivery. Various characterizations such as Fourier transform infrared spectroscopy, differential scanning calorimetry, TGA, powder X‐ray diffraction, and scanning electron microscopy were performed to confirm the cross‐linking of functional groups, thermal stability, crystal structure, and surface morphology of developed formulations. Swelling and drug release was performed at higher and lower pH (1.2, 7.4) buffer solution. Increase in swelling was observed at higher pH 7.4. Cumulative percent release of 5‐FU and LC was 29.8% and 27.2% at pH 1.2, and 86.9% and 87.01% at pH 7.4, respectively. Kinetic modeling was applied on optimized hydrogel formulation, and the results showed that release of 5‐FU and LC best expressed by first‐order kinetic model with regression coefficient (R2) value 0.937 for 5‐FU and 0.963 for LC. Acute oral toxicity was performed on healthy rabbits, and results showed that the synthesized CCDDS is nontoxic and compatible with biological system. In vivo studies on rabbits were conducted using HPLC, and plasma drug concentration and pharmacokinetic parameters were estimated. Newly synthesized CCDDS showed a good pH‐responsive swelling and controlled drug delivery characteristics. CCDDS can be used as excellent carrier for various therapeutic agents, which are compatible with biological system.

<p>Development and in vitro evaluation of (β-cyclodextrin-g-methacrylic acid)/Na⁺-montmorillonite nanocomposite hydrogels for controlled delivery of lovastatin</p>

“…Furthermore, the shape of spleen cells remained unaltered in both control as well as treated group with β-CD-g-poly (MAA) nanocomposite networks. Various researchers from Pakistan have already conducted toxicity studies to ensure safety of living systems against developed crosslinked networks ie, β-CD-g-MAA hydrogel microparticles (Mahmood et al, 2016), polyvinyl alcohol and itaconic acid–g–MAA combinatorial networks (Orva et al, 2018), cellulose acetate phthalate–g–MAA networks (Shah et al, 2018), and chondroitin sulfate–g–MAA (Barkat et al, 2018) etc 34–36. Our results were comparable with the findings of these studies.…”

Synthetic hydrogels: Synthesis, novel trends, and applications

“…However, it is difficult to obtain the optimum monomer sequence or number of cross‐links to yield the desired properties; hence combinatorial synthesis can be used. In combinatorial synthesis, a series of different compositions of monomers, modifiers, cross‐linkers, and so forth, can be used 164,165 …”

pH-Responsive Nanocomposite Based Hydrogels for the Controlled Delivery of Ticagrelor; In Vitro and In Vivo Approaches

“…Thus, NCHs can be used safely for oral delivery of TG due to their non-toxic nature. 16,22,26 The pharmacokinetic evaluation revealed that C max of both NCH1 and NCH2 showed a 6.5 and 7.2 fold increment, respectively. T max increased from 2 hrs (pure TG) to 6 hrs for both NCH formulations.…”