QBD approach for the development of hesperetin loaded colloidal nanosponges for sustained delivery: In-vitro, ex-vivo, and in-vivo assessment

Hesperetin (HT) is a polyphenolic compound with anti-carcinogenic, tumor necrosis, and anti-oxidant properties. The present study reports the fabrication, optimization, and evaluation of HT-loaded nanosponges (HTN)- based gel (HTNG) for sustained anti-inflammatory effect. HTN formulation was prepared by quasi emulsion solvent diffusion method using a 42 factorial design. HTN was subjected to different solid and liquid state characterizations and subsequently loaded in carbopol gel. The effects of pro-inflammatory cytokines (IL- 1β and IL-6) were evaluated using RAW 264.7 macrophage cells, and the anti-inflammatory potential was tested in rats. Tiny, porous, and spherical HTN retarded the drug release (39.98%) up to 8 h compared to the pure drug (70.74%) and physical mixture (73.72%) and followed the Higuchi-matrix model. HTNG had a strong downregulating effect on cytokines. It showed no skin irritation and 18.52% skin permeation at 8 h. Further, HTNG-treated rats exhibited 33.16% inflammation inhibition compared to the control group. In conclusion, nanosponges significantly retarded the topical delivery and could circumvent the bioavailability issues associated with HT.