Nestorone nanosuspension-loaded dissolving microneedles array patch: A promising novel approach for "on-demand" hormonal female-controlled peritcoital contraception

Altuntas E., Tekko I. A., Vora L. K., Kumar N., Brodsky R., Chevallier O., ...More

INTERNATIONAL JOURNAL OF PHARMACEUTICS, vol.614, 2022 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 614
  • Publication Date: 2022
  • Doi Number: 10.1016/j.ijpharm.2021.121422
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Aquatic Science & Fisheries Abstracts (ASFA), BIOSIS, Biotechnology Research Abstracts, CAB Abstracts, EMBASE, International Pharmaceutical Abstracts, MEDLINE, Veterinary Science Database
  • Keywords: Bilayer dissolving microneedles, Nanosuspension, Intradermal, Nestorone, Pericoital contraception, IN-VITRO, TRANSDERMAL DELIVERY, PROGESTIN ST-1435, OVARIAN-FUNCTION, LEVONORGESTREL, FORMULATION, IMPLANTS, WOMEN, MODEL, SKIN
  • Istanbul University Affiliated: Yes


"On demand " hormonal female-controlled pericoital contraception is one strategy which could be used to minimize the impact of unintended pregnancy. Nestorone (NES) is a potent contraceptive, with relatively few side effects in comparison with other contraceptives. NES presents an attractive option for "on demand " pericoital contraceptive. Unfortunately, the drug is inactive if taken orally, but it has high progestational activity and antiovulatory potency if administered parenterally. Current drug delivery systems, such as a transdermal hydrogel are not so satisfactory. Dissolving microneedles array (DMNs) are an attractive alternative, minimally invasive, delivery system. In this study, we report, for the first time, development of tip-loaded NES-nanosuspension (NES-NS)-loaded bilayer DMNs to deliver NES intradermally for subsequent release. NES-NS was prepared and optimised, freeze-dried and then used to fabricate DMNs using a blend of two biocompatible polymers, namely poly(vinyl alcohol) and poly(vinyl pyrrolidone). Both NES-NS and the NES-NS-loaded DMNs were fully characterised and the performance of the DMNs was evaluated in vivo using Sprague Dawley rats. Results showed that the finalised NES-NS had particle size and PDI values of 666.06 & PLUSMN; 1.86 nm and 0.183 & PLUSMN; 0.01, respectively. The NES-NS-DMNs had relatively high tips-localised drug loading (approximately 2.26 & PLUSMN; 1.98 mg/array) and exhibited satisfactory mechanical and insertion properties. In Sprague Dawley rats, DMNs delivered NES into the skin, with the drug then appearing in blood and rapidly reaching its maximum concentration (C-max of 32.68 & PLUSMN; 14.06 ng/mL) within 1 h post-DMNs application. Plasma levels above 3.4 ng/mL were maintained for 2 days. This suggests that DMNs are a promising drug delivery system that could be used to deliver NES as an "On demand " hormonal female-controlled pericoital contraceptive.