Development of dissolving microneedles for intradermal delivery of the long-acting antiretroviral drug bictegravir

Oral administration and intramuscular (IM) injection are commonly recommended options for human immunodeficiency virus (HIV) treatment. However, poor patient compliance due to daily oral dosing, pain at injection sites and the demand for trained healthcare staff for injections limit the success of these administration routes, especially in low-resource settings. To overcome these limitations, for the first time, we propose novel bilayer dissolving microneedles (MNs) for the intradermal delivery of long-acting nanosuspensions of the antiretroviral (ARV) drug bictegravir (BIC) for potential HIV treatment and prevention. The BIC nanosuspensions were prepared using a wet media milling technique on a laboratory scale with a particle size of 358.99 ± 18.53 nm. The drug loading of nanosuspension-loaded MNs and BIC powder-loaded MNs were 1.87 mg/0.5 cm² and 2.16 mg/0.5 cm², respectively.

Both dissolving MNs exhibited favorable mechanical and insertion ability in the human skin simulant Parafilm® M and excised neonatal porcine skin. Importantly, the pharmacokinetic profiles of Sprague Dawley rats demonstrated that dissolving MNs were able to intradermally deliver 31% of drug loading from nanosuspension-loaded MNs in the form of drug depots. After a single application, both coarse BIC and BIC nanosuspensions achieved sustained release, maintaining plasma concentrations above human therapeutic levels (162 ng/mL) in rats for 4 weeks. These minimally invasive and potentially self-administered MNs could improve patient compliance, providing a promising platform for the delivery of nanoformulated ARVs and resulting in prolonged drug release, particularly for patients in low-resource settings.

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Materials

Poly(vinyl alcohol) (PVA) with a molecular weight of 9–10 kDa and poly(vinylpyrrolidone) (PVP) with molecular weights of 58 kDa and 360 kDa were purchased from Sigma Aldrich, Steinheim, Germany. Bidistilled glycerol was purchased from VWR International, Leicestershire, UK. BIC was purchased from Enke Pharma-tech Co., Ltd, Cangzhou, China. All other reagents used in this work were of analytical reagent grade.

Chunyang Zhang, Lalitkumar K. Vora, Ismaiel A. Tekko, Fabiana Volpe-Zanutto, Ke Peng, Alejandro J. Paredes, Helen O. McCarthy, Ryan F. Donnelly, Development of dissolving microneedles for intradermal delivery of the long-acting antiretroviral drug bictegravir, International Journal of Pharmaceutics, Volume 642, 2023, 123108, ISSN 0378-5173, https://doi.org/10.1016/j.ijpharm.2023.123108.

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