Simon Benita

A. Badihi, M. Frušić-Zlotkin, Y. Soroka, S. Benhamron, T. Tzur, T. Nassar, and S. Benita. 2020. “Topical nano-encapsulated cyclosporine formulation for atopic dermatitis treatment: Topical cyclosporine NCs for AD.” Nanomedicine: Nanotechnology, Biology, and Medicine, 24. Publisher's Version Abstract
Systemic cyclosporine A (CsA) therapy shows efficacy in the treatment of recalcitrant severe atopic dermatitis (AD) but elicits severe side-effects. Thus, a topical formulation of CsA nanocapsules (NCs), able to potentially bypass these drawbacks, was developed. CsA-NCs were shown to enhance drug penetration into the various layers of porcine ear skin. Furthermore, the encapsulated CsA was biologically active, as shown in vitro on mouse splenocytes, reflected by inhibition of both cell proliferation and of interleukin (IL)-2 secretion. Ex-vivo efficacy was demonstrated on human skin organ culture by markedly reducing pro-inflammatory cytokines secretion. Finally, CsA-NCs topical formulation elicited improved efficacy in terms of better preservation of the skin barrier integrity, a decrease of the systemic pro-inflammation markers and reduced skin inflammation. The overall results suggest that this original topical platform may provide a novel therapeutic tool of clinical significance compared to the existing topical therapeutic drugs in AD. © 2019 Elsevier Inc.
T. Nassar, A. Rohald, N. Naraykin, D. Barasch, O. Amsalem, P. Prabhu, M. Kotler, and S. Benita. 2019. “Nanocapsules embedded in microparticles for enhanced oral bioavailability and efficacy of Lopinavir as an anti-AIDS drug.” Journal of Drug Targeting, 27, 5-6, Pp. 590-600. Publisher's Version Abstract
Lopinavir (LPV), an efficient drug for HIV infection treatment, was incorporated into biodegradable PLGA nanocapsules (NCs) embedded in microparticles (MCPs) using the spray-drying technique in an attempt to bypass the P-gp efflux and protect the drug from CYP3A pre-systemic metabolism without ritonavir (RTV). SEM observations confirmed the formation of NCs and their entrapment in the MCPs. LPV-loaded NCs and free LPV were released from the MCPs at pH of 7.4 as evidenced by in vitro release studies. Results obtained from rat studies showed a two-fold higher bioavailability of LPV following oral administration of the optimal formulation than Kaletra®, the marketed drug, showing that when properly entrapped, LPV can be effectively protected from CYP degradation in the gut as well as from the liver following systemic absorption. It was also shown that serum derived from rats following LPV oral administration in two formulations and Kaletra® significantly decreased the multiplication of HIV-1 in cultured SupT1 cells. Furthermore, the LPV formulations markedly restricted the titre of infectious HIV-1 production compared with Kaletra® confirming the improved antiviral activity of LPV delivered in the rat blood circulation by the nanocapsules embedded in microparticle formulations. © 2018, © 2018 Informa UK Limited, trading as Taylor & Francis Group.