Utilization of propranolol hydrochloride mucoadhesive invasomes as a locally acting contraceptive: <i>in-vitro</i>, <i>ex-vivo,</i> and <i>in-vivo</i> evaluation

Abstract

It was found that propranolol hydrochloride (PNL), which is a beta-blocker used for hypertension treatment, has a potent spermicidal activity through local anesthetic activity or beta-blocking effect on sperm cells subsequently it could be used as a contraceptive remedy. This study aimed to entrap PNL into invasomes (INVs) and then formulate it as a locally acting contraceptive gel. PNL-loaded mucoadhesive INVs were prepared via the thin-film hydration technique. The D-optimal design was utilized to fabricate INVs employing lipid concentration (X₁), terpenes concentration (X₂), terpenes type (X₃), and chitosan concentration (X₄) as independent variables, while their impact was observed for entrapment efficiency percent (Y₁; EE%), particle size (Y₂; PS), zeta potential (Y₃; ZP), and amount of drug released after 6 h (Y₄; Q6h). Design Expert® was bestowed to nominate the desired formula. The selected INV was subjected to further studies and formulated into a mucoadhesive gel for <i>ex-vivo</i> and <i>in-vivo</i> investigations. The optimum INV showed a spherical shape with EE% of 65.01 ± 1.24%, PS of 243.75 ± 8.13 nm, PDI of 0.203 ± 0.01, ZP of 49.80 ± 0.42 mV, and Q6h of 53.16 ± 0.73%. Differential scanning calorimetry study asserted the capability of INVs to entrap PNL. Permeation studies confirmed the desired sustained effect of PNL-loaded INVs-gel compared to PNL-gel, INVs, and PNL solution. Sperm motility assay proved the potency of INVs-gel to inhibit sperm motility. Besides, the histopathological investigation verified the tolerability of the prepared INVs-gel. Taken together, the gained data justified the efficacy of PNL-loaded INVs-gel as a potential locally acting contraceptive.