Nanoparticle-in-Microparticle Drug Delivery System of An Antiretroviral Drugs Combination

David Wang Auditorium, 3rd floor Dalia Maydan Bldg.
Mrs. Roni Sverdlov, M.Sc. Candidate

Mrs. Roni Sverdlov, M.Sc. Candidate

Laboratory of Pharmaceutical Nanomaterials Science, Department of Materials Science and Engineering, Technion-Israel. Haifa 320000

During the last decade, many attempts have been made to eradicate human immunodeficiency (HIV). However, eradication of HIV is highly unlikely, and effective antiretroviral therapy is required on a long-term basis to maintain viral suppression and reduce disease progression [1]. Darunavir (DAR) is a poorly water-soluble gold-standard antiretroviral of the protease inhibitors family used in the anti-HIV cocktail that dissolves under the low pH conditions of the stomach. DAR undergoes efflux in the intestinal epithelium and metabolism that decrease its oral bioavailability and displays short half-life in plasma. To improve its pharmacokinetics, DAR is co-administered with the boosting agent ritonavir (RIT) that inhibits both the efflux and the metabolism. However, its pharmacokinetics remains suboptimal. Nanotechnology based approaches offer unique opportunities to improve the aqueous solubility, stability, bioavailability and targeting of antiretroviral drugs in order to reduce their costs and increase patient compliance.[1] In this work, we investigated a modular mucoadhesive nanoparticle-in-microparticle delivery system based on the encapsulation of pure drug nanoparticles within film-coated microparticles made of natural polymers for the oral administration of a clinically relevant antiretroviral drug combination. After the development of a semi-continuous production method, we assessed the oral pharmacokinetics of DAR using the novel delivery approach and compared it with that of the unprocessed drugs and the pure drug nanoparticles in rats. Results indicated that microencapsulation prevented the dissolution of the drugs in the stomach and ensured its release in the intestine, leading to a 2.3-fold increase of the oral bioavailability with respect to the pristine and nanonized (though not microencapsulated) drugs.

  1. Sosnik A, Augustine R. Challenges in oral drug delivery of antiretrovirals and the innovative strategies to overcome them. Adv Drug Deliv Rev 103 (2016) 105-120.

Supervisor: Assoc. Prof. Alejandro Sosnik