Karaya Gum-Containing Thermosensitive Hydrogels for Controlled Release of Lidocaine in Short- and Long-Term Analgesia

Natural gums are widely available, biocompatible polymers that can be strategically employed to design novel stimuli-responsive materials to fulfill the specific requirements of the drug delivery carriers. This study developed multifunctional semi-interpenetrating networks (s-IPNs) by integrating karaya gum (KG), a bioactive adhesive biopolymer, with a thermosensitive poly(N-isopropylacrylamide) (pNIPAAm) network. KG improved the compressive strength of pNIPAAm up to threefold and enhanced the hydrogel swelling at pH 7.4 and 5.5, at 25 and 37 °C. The s-IPNs exhibited a lower volume phase transition temperature than pNIPAAm alone. Additionally, KG increased the lidocaine hydrochloride (LH)-entrapment efficiency of the s-IPN to 65% compared to 47% in the hydrogel without KG. The synergistic effect of KG content, LH loading, and physiological skin conditions (pH 5.5, 37 °C) enhanced the bioadhesiveness of the hydrogels. Notable, 71% of the drug was released from the s-IPN in its relaxed state within 3 h under normal skin conditions, while 80% of LH was delivered sustainably over 17 h from initially dehydrated s-IPN. The dual temperature- and pH-responsive s-IPNs demonstrated the promising potential for biomedical applications, particularly for controlled LH release, supporting both short- and long-term analgesic effects.