Thermosensitive polymers-based injectable hydrogels: a quantitative validations design utilized for controlled delivery of gefitinib anticancer drug

A.A.H. Abdellatif, A. Al-Subaiyel, A.M. Mohammed

Department of Pharmaceutics, College of Pharmacy, Qassim University, Qassim, Saudi Arabia. a.abdellatif@qu.edu.sa

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• Pharmacology

OBJECTIVE: Gefitinib (GFB) was loaded into different designs of thermos- and pH-responsive polymer-based hydrogels, namely chitosan (CH) and Pluronic F127 (Pl F127) with the aid of a crosslinking β-glycerophosphate (β-GP).

MATERIALS AND METHODS: GFB was loaded in CH and P1 F127 hydrogel. The preparation was characterized and tested for their stability and efficacy as antitumor injectable therapy devices. The antiproliferative effect of the selected CH/β-GP hydrogel formula was investigated against the hepatic cancerous cell, HepG2 using the MTT tetrazolium salt colorimetric assay. Furthermore, the pharmacokinetic was performed for GEF using a developed, reported and validated LC method.

RESULTS: All hydrogel samples showed no changes in color, separation(s), and crystallization in both liquid and gel forms. The CH/β-GP system showed a lower viscosity (110.3 ± 5.2 Cp) compared to CH/β-GP/Pl F127 system (148.4 ± 4.4 Cp) in the sol phase. Also, the results confirmed a continued increase in rats’ plasma during the first four days (Tmax) with a plasma peak level (Cmax) of 3.663 μg/mL followed by a decrease below the detection limit after 15 days. Moreover, the results indicated no significant difference (p < 0.05) between the predicted and observed GEF-concentration data and that the proposed CH-based hydrogel facilitated its sustained release as distinguished from the longer value of MRT of 9 days and an AUC0-t of 41.917 μg/L/day.

CONCLUSIONS: The medicated CH/β-GP hydrogel formula had a higher targeting-controlled efficiency against a solid tumor than the free poor water soluble GFB.

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