G-3327

Preparation and evaluation of minoxidil and azelaic acid invasome with cineole and limonene

 Tahereh Dara ¹ ©, Mohsen Zabihi ², Hamid Bahreini ³, Ana Amaninezhad ⁴ ℗   

 
Abstract

Introduction: New drug delivery systems, such as invasomes, are being explored for treating male pattern baldness. Topical minoxidil is the only FDA-approved drug for hair growth, while azelaic acid helps normalize keratinization in skin and hair cells. Combining minoxidil with azelaic acid can increase drug concentration by enhancing minoxidil's solubility. Invasomes are advanced liposome-based systems, incorporating terpenes to improve vesicle flexibility and cellular penetration. This study prepared an invasome formulation of minoxidil and azelaic acid using the terpenes limonene and cineole to enhance skin delivery, reduce the side effects of irritation, and increase the effectiveness of minoxidil. Materials and Methods: In this study, different formulations were prepared with specified amounts of minoxidil, cineole, lecithin, and limonene. The formulations were evaluated in terms of average particle size, polydispersity index, zeta potential, drug loading percentage, and in vitro release rate. Also, at the end of the study, the effect of different formulations on hair growth in Wistar rats was evaluated and the results were reported as the weight of hair grown in the treated area. Results: The results showed that formulation 4 with an average diameter of 112.4 nm had the smallest particle size and formulation 2 with an average diameter of 181.9 nm had the largest particle size. The average zeta potential in all formulations was estimated between -14.8 and -29.4 mV, with the lowest value being for formulation 5 and the highest value being for formulation 3. The lowest polydispersity index (PI) was for formulation 6 (0.201) and the highest index was for formulation 5 (1.64). The entrapment percentage of all formulations was above 80%, although formulation 3 had the highest entrapment percentage with 90.5%. The highest drug release percentage in the dialysis bag and in vitro conditions after 4 hours was for formulation 6 with about 85%, respectively. The R2 value of the drug release kinetics in all formulations in vitro and in the dialysis, bag was most consistent with the Higuchi model. Also, the results of the effect of the produced formulations on hair growth in laboratory rats showed that the invasome prepared with limonene had the highest hair growth rate, followed by cineole. Invasome containing both of these compounds were able to significantly increase the weight of hair grown at the treatment area compared to the control group (P0.05). Discussion and Conclusion: Based on the results, it is possible to make an invasome formulation of minoxidil, and these invasomes, with the presence of two terpenoids, cineole and limonene, allow for more absorption of the drug minoxidil, which can consequently increase hair growth.

Keywords: Invasome, minoxidil, azelaic acid, limonene, cineole