Ciprofibrate-Loaded Nanoparticles Prepared by Nanoprecipitation: Synthesis, Characterization, and Drug Release

Author(s)

Gomes Quintino Correa, Raissa Lohanna ^[1] ; dos Santos, Renan ^[1] ; Calumby Albuquerque, Lindomar Jose ^{[1, 2]} ; Barros de Araujo, Gabriel Lima ^[3] ; Chante Edwards-Gayle, Charlotte Jennifer ^[4] ; Ferreira, Fabio Furlan ^{[1, 5]} ; Costa, Fanny Nascimento ^{[1, 4]}

Affiliation

^[1] Fed Univ ABC UFABC, Ctr Nat & Human Sci CCNH, BR-09210580 Santo Andre, SP - Brazil

^[2] Brazilian Ctr Res Energy & Mat CNPEM, Brazilian Synchrotron Light Lab LNLS, BR-13083170 Campinas - Brazil

^[3] Univ Sao Paulo, Fac Pharmaceut Sci, Dept Pharm, BR-05508900 Sao Paulo - Brazil

^[4] Diamond Light Source, Harwell Sci & Innovat Campus, Didcot OX11 0DE, Oxon - England

^[5] Fed Univ ABC UFABC, Nanomed Res Unit NANOMED, BR-09210580 Santo Andre, SP - Brazil

• Document type: Journal article
• Source: POLYMERS; v. 13, n. 18 SEP 2021.
• Web of Science Citations: 0

Abstract

Ciprofibrate (CIP) is a highly lipophilic and poorly water-soluble drug, typically used for dyslipidemia treatment. Although it is already commercialized in capsules, no previous studies report its solid-state structure; thus, information about the correlation with its physicochemical properties is lacking. In parallel, recent studies have led to the improvement of drug administration, including encapsulation in polymeric nanoparticles (NPs). Here, we present CIP's crystal structure determined by PXRD data. We also propose an encapsulation method for CIP in micelles produced from Pluronic P123/F127 and PEO-b-PCL, aiming to improve its solubility, hydrophilicity, and delivery. We determined the NPs' physicochemical properties by DLS, SLS, ELS, SAXS and the loaded drug amount by UV-Vis spectroscopy. Micelles showed sizes around 10-20 nm for Pluronic and 35-45 nm for the PEO-b-PCL NPs with slightly negative surface charge and successful CIP loading, especially for the latter; a substantial reduction in zeta-potential may be evidenced. For Pluronic nanoparticles, we scanned different conditions for the CIP loading, and its encapsulation efficiency was reduced while the drug content increased in the nanoprecipitation protocol. We also performed in vitro release experiments; results demonstrate that probe release is driven by Fickian diffusion for the Pluronic NPs and a zero-order model for PEO-b-PCL NPs. (AU)

• FAPESP's process: 16/23844-8 - Biodegradable and pH-responsive polymersomes for gene and protein delivery
• Grantee: Lindomar Jose Calumby Albuquerque
• Support Opportunities: Scholarships in Brazil - Doctorate