In-vitro and in-vivo evaluation of biocompatible polymeric microgels for pH- driven delivery of Ketorolac tromethamine.

The aim of the current study was to prepare glutamic acid crosslinked poly(itaconic acid/methacrylic acid) microgels for pH-responsive delivery of ketorolac tromethamine, using aqueous free radical polymerization technique. The polymerization of polymer with monomers was carried out by a crosslinking agent N', N'-methylene bisacrylamide in the presence of initiator ammonium persulfate. The prepared microgels were characterized for structure, surface morphology, thermal stability, and crystallinity. Similarly, studies such as sol-gel analysis, drug loading, and polymer volume fraction were performed for the fabricated microgels. The pH-sensitivity of the developed microgels was investigated at three different pH values i.e., pH 1.2, 4.6, and 7.4 by swelling and in-vitro drug release studies. Maximum swelling and drug release were found at pH 7.4 as compared to pH 1.2 and 4.6, which indicated the pH-sensitive nature of the prepared microgels. The toxicity of the prepared microgels was evaluated by cell line and HET-CAM test, which demonstrated no toxic effect of the prepared microgels. In-vivo study was carried out on rabbits and high plasma concentration was reported for the drug loaded microgels as compared to drug solution and commercial product Keten. Hence, the prepared microgel system could be employed as an excellent carrier for the controlled drug delivery system.

Synthesis, Characterization, In-Vitro and In-Vivo Evaluation of Ketorolac Tromethamine-Loaded Hydrogels of Glutamic Acid as Controlled Release Carrier.

Glutamic acid-co-poly(acrylic acid) (GAcPAAc) hydrogels were prepared by the free radical polymerization technique using glutamic acid (GA) as a polymer, acrylic acid (AAc) as a monomer, ethylene glycol dimethylacrylate (EGDMA) as a cross-linker, and ammonium persulfate (APS) as an initiator. Increase in gel fraction was observed with the increasing concentration of glutamic acid, acrylic acid, and ethylene glycol dimethylacrylate. High percent porosity was indicated by developed hydrogels with the increase in the concentration of glutamic acid and acrylic acid, while a decrease was seen with the increasing concentration of EGDMA, respectively. Maximum swelling and drug release was exhibited at high pH 7.4 compared to low pH 1.2 by the newly synthesized hydrogels. Similarly, both swelling and drug release increased with the increasing concentration of glutamic acid and acrylic acid and decreased with the increase in ethylene glycol dimethylacrylate concentration. The drug release was considered as non-Fickian transport and partially controlled by viscoelastic relaxation of hydrogel. In-vivo study revealed that the AUC0-∞ of fabricated hydrogels significantly increased compared to the drug solution and commercial product Keten. Hence, the results indicated that the developed hydrogels could be used as a suitable carrier for controlled drug delivery.

Fabrication of alginate based microgels for drug-sustained release: In-vitro and in-vivo evaluation.

The current study was conducted to evaluate and analyze the effect of alginate, itaconic acid, and N,N'-methylene bisacrylamide in formulation of a novel alginate based microgels for sustained release of theophylline. The fabricated microgels were characterized by PXRD, SEM, FTIR, TGA and DSC respectively. FTIR revealed that alginate reacted with itaconic acid during polymerization reaction and confirmed the overlapping of itaconic acid on the backbone of alginate. TGA and DSC depicted high thermal stability of the fabricated microgels as compared to pure unreacted polymer and monomer. Likewise, dynamic swelling and percent drug release studies were carried out at different pH media i.e., pH 1.2, 4.6 and 7.4 respectively. Greater dynamic swelling and percent drug release was observed at higher pH 7.4 as compared to lower pH 4.6 and 1.2 due to the deprotonation of COOH groups of both alginate and itaconic acid respectively. The drug release mechanism from the fabricated microgels could be described by first order model. In-vivo pharmacokinetic study was performed on rabbits and exhibited sustained release in rabbits. Hence, the developed microgels indicated higher potential as the delivery system for the sustained delivery of theophylline.

Improved skin permeability and whitening effect of catechin-loaded transfersomes through topical delivery.

The aim of the study was to prepare catechin-loaded transfersomes to enhance drug permeability through topical administration for the skin protection against ultraviolet radiation induced photo-damage. The results showed that the catechin-loaded transfersomes were monodispersed with polydispersity index (PDI) < 0.2, <200 nm in particle size and with high encapsulation efficiency (E.E.%) greater than 85%. The in vitro skin permeation test indicated that the catechin-loaded transfersomes enhanced the skin permeability by 85% compared to the catechin aqueous solution. Similarly, the in-vivo skin whitening study demonstrated that F5 transfersome formulation was effective in tyrosinase inhibition and had good biocompatibility to the guinea pig skin. Finally, the stability study showed that both physicochemical properties and E.E.% of the F5 transferosome formulation were fairly stable after 3 months storage. Therefore, topical administration of catechin-loaded transfersomes could be considered as a potential strategy for the treatment of UV-induced oxidative damage to the skin.

Synthesis and In Vitro Evaluation of Aspartic Acid Based Microgels for Sustained Drug Delivery.

The main focus of the current study was to sustain the releasing behavior of theophylline by fabricated polymeric microgels. The free radical polymerization technique was used for the development of aspartic acid-co-poly(2-acrylamido-2-methylpropanesulfonic acid) microgels while using various combinations of aspartic acid, 2-acrylamido-2-methylpropanesulfonic acid, and N',N'-methylene bisacrylamide as a polymer, monomer, and cross-linker, respectively. Ammonium peroxodisulfate and sodium hydrogen sulfite were used as initiators. Characterizations such as DSC, TGA, SEM, FTIR, and PXRD were performed for the fabricated microgels to assess their thermal stability with unreacted polymer and monomer, their surface morphology, the formation of a new polymeric system of microgels by evaluating the cross-linking of functional groups of the microgels' contents, and to analyze the reduction in crystallinity of the theophylline by fabricated microgels. Various studies such as dynamic swelling, drug loading, sol-gel analysis, in vitro drug release studies, and kinetic modeling were carried out for the developed microgels. Both dynamic swelling and percent drug release were found higher at pH 7.4 as compared to pH 1.2 due to the deprotonation of functional groups of aspartic acid and AMPS. Similarly, sol-gel analysis was performed and an increase in gel fraction was observed with the increasing concentration of microgel contents, while sol fraction was decreased. Conclusively, the prepared carrier system has the potential to sustain the release of the theophylline for an extended period of time.