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. 2022 Dec;29(1):2549-2560.
doi: 10.1080/10717544.2022.2100514.

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

Mahmoud H Teaima  1 , Moaz A Eltabeeb  2 , Mohamed A El-Nabarawi  1 , Menna M Abdellatif  2
Affiliations

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

Mahmoud H Teaima et al. Drug Deliv. 2022 Dec.

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; spermicide; vaginal drug delivery.

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Conflict of interest statement

No potential conflict of interest was reported by the authors.

Figures

Figure 1.
Figure 1.
Effect of formulation variables on EE% of PNL-INVs (a-b) and PS (c-d). EE%: Entrapment Efficiency Percentage, PS: Particle Size, PNL: Propranolol Hydrochloride, INVs: Invasomes.
Figure 2.
Figure 2.
Effect of formulation variables on ZP of PNL-INVs (e-f) and Q6h (g-h). ZP: Zeta Potential, Q6h: Amount of drug released after six hours, PNL: Propranolol Hydrochloride, INVs: Invasomes.
Figure 3.
Figure 3.
Transmission electron micrographs of INV14. INVs: Invasomes.
Figure 4.
Figure 4.
DSC thermograms of PNL, PC and the optimum INV. PC: Phospholipid, PNL: Propranolol Hydrochloride, INV: Invasome.
Figure 5.
Figure 5.
Ex-vivo permeation profile of PNL from INV-gel, PNL-gel, INV14 compared to PNL solution. PNL: Propranolol Hydrochloride, INV: Invasome.
Figure 6.
Figure 6.
Light microscope photomicrographs showing sperm cells A) before addition of PNL-INV gel B) after addition of PNL-INV gel. PNL: Propranolol Hydrochloride, INV: Invasome.
Figure 7.
Figure 7.
Light microscope photomicrographs showing histopathological sections (hematoxylin and eosin stained) of rat vagina normal control (group I), rat vagina treated with PNL gel (group II) and rat vagina treated with INVs gel (group III) with magnification power of 16X to illustrate all vagina layers (Left side) and magnification power of 40X (Right side). PNL: Propranolol Hydrochloride, INV: Invasome.
See this image and copyright information in PMC

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