Development of pH-Sensitive Chitosan-g-poly(acrylamide-co-acrylic acid) Hydrogel for Controlled Drug Delivery of Tenofovir Disoproxil Fumarate

The present study aimed to develop a pH-sensitive chitosan-based hydrogel for controlled delivery of an anti-hepatitis B drug, tenofovir disoproxil fumarate (TDF). Free radical polymerization was utilized to graft acrylamide and acrylic acid using N,N-methylene bisacrylamide as the crosslinker. Physicochemical characterization confirmed the synthesis of thermally stable chitosan-g-poly(acrylamide-co-acrylic acid) hydrogels with well-defined pores within a fibrous surface.

The prepared hydrogels exhibited pH and ionic strength sensitivity, with the swelling significantly lower under acidic and strong ionic strength conditions but higher in neutral and basic solutions. In addition, cytotoxicity studies on HeLa cell lines proved the cytocompatibility of the drug delivery material and its readiness for physiological applications. The encapsulation of TDF in the hydrogels was optimized and an encapsulation efficiency and a drug loading percentage of 96% and 10% were achieved, respectively.

More interestingly, in vitro release studies demonstrated a pH-dependent release of TDF from hydrogels. The release at pH 7.4 was found to be up to five times higher than at pH 1.2 within 96 h. This further suggested that the newly developed hydrogel-loaded TDF could be proposed as a smart delivery system for oral delivery of anti-hepatitis B drugs.

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Materials: Chitosan low molecular weight (CS), acrylic acid (AA), N,N methylene bisacrylamide (MBA), Mono-potassium phosphate (KH₂PO₄), and sodium phosphate dibasic (Na₂HPO₄) were purchased from Sigma-Aldrich (Darmstadt, Germany). Tenofovir disoproxil fumarate (TDF) was donated by Aspen Pharmacare (Durban, South Africa). Acrylamide (AAm), hydrogen chloride (HCl), and HPLC grade acetonitrile were purchased from Merck (Darmstadt, Germany). Ammonium persulfate and orthophosphoric acid were purchased from Saarchem (Wadeville, South Africa). Glacial acetic acid, sodium hydroxide (NaOH), magnesium chloride (MgCl₂), sodium chloride (NaCl), potassium chloride (KCl), methanol, and acetone were purchased from Minema (Roodepoort, South Africa). Almunium chloride (AlCl₃) was purchased from Fluka Chemika (Buchs, Switzerland). Ultra-pure water was HPLC grade 18 mega Ohm water, prepared using a Milli-Q academic A10 water purification system (Millipore^® Bedford, MA, USA).

Article information: Safari, J.B.; Bapolisi, A.M.; Krause, R.W.M. Development of pH-Sensitive Chitosan-g-poly(acrylamide-co-acrylic acid) Hydrogel for Controlled Drug Delivery of Tenofovir Disoproxil Fumarate. Polymers 2021, 13, 3571. https://doi.org/10.3390/polym13203571