Utilization of propranolol hydrochloride mucoadhesive invasomes as a locally acting contraceptive: in-vitro, ex-vivo, and in-vivo 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 ex-vivo and in-vivo 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.

Keywords

• Contraception
• histopathological study
• mucoadhesive invasomes
• propranolol hydrochloride
• vaginal drug delivery
• spermicide