Preparation, characterization and evaluation of biological activity of inclusion complexes and nanoclusters of cyclodextrins self-assembled to increase the solubility of poorly soluble drugs

• Grant number: 13/15704-3
• Support Opportunities: Regular Research Grants
• Start date: March 01, 2014
• End date: June 30, 2016
• Field of knowledge: Health Sciences - Pharmacy - Pharmaceutical Technology
• Principal Investigator: Leticia Norma Carpentieri Rodrigues
• Grantee: Leticia Norma Carpentieri Rodrigues
• Host Institution: Instituto de Ciências Ambientais, Químicas e Farmacêuticas (ICAQF). Universidade Federal de São Paulo (UNIFESP). Campus Diadema. Diadema , SP, Brazil
• Associated researchers: Adriana Karla Cardoso Amorim Reis ; Daniela Goncales Galasse Rando ; Luciana Morita Katiki ; Paulo Roberto Regazi Minarini

Abstract

In general, the bioavailability of poorly soluble drugs have variable and incomplete. Benzimidazole (BZD) is one of the most privileged structures of medicinal chemistry, exhibiting a broad biological activity, however, the low solubility of this substance has caused inefficiency and emergence of resistance. Cyclodextrins (CDs) are known to increase the solubility, dissolution efficiency and bioavailability of various drugs through the formation of inclusion complex. Recently it has been observed that other types of CD complexes, such as non-inclusion complexes, are also participating in the CD solubilization of poorly soluble drugs. The present work aims to form and characterize inclusion complexes between CDs and BZD (fenbendazole and albendazole) in the presence or absence of water-soluble polymer (PVP) and evaluate the impact of training and nanoclusters of CDs on the solubility of these drugs. Solid systems equimolar drugs with CDs in the absence (BZD: CD) or the presence of water-soluble polymer (BZD:CD/PVP) will be prepared by coevaporation. Testing phase solubility and intrinsic dissolution will be conducted to verify the influence of CDs and / or water-soluble polymer on the solubility of the drugs. Molecular modeling studies and 1H-NMR will be performed to assess the viability of the formation as well as the more favorable conformations of the "inclusion complex." Differential Scanning Calorimetry, X-ray diffraction, scanning electron microscopy and particle size distribution by laser diffraction are used to characterize the systems solid. The biological activity of antiparasitic will be evaluated by testing the hatching of eggs and development testing and larval motility. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

PACHECO, P. A.; RODRIGUES, L. N. C.; FERREIRA, J. F. S.; GOMES, A. C. P.; VERISSIMO, C. J.; LOUVANDINI, H.; COSTA, R. L. D.; KATIKI, L. M.. Inclusion complex and nanoclusters of cyclodextrin to increase the solubility and efficacy of albendazole. Parasitology Research, v. 117, n. 3, p. 705-712, MAR 2018. (13/15704-3)

CARPENTIERI RODRIGUES, LETICIA NORMA; MORAES TAVARES, ANNA CAROLLINA; FERREIRA, BEATRIZ TAVARES; CARDOSO AMORIM REIS, ADRIANA KARLA; KATIKI, LUCIANA MORITA. Inclusion complexes and self-assembled cyclodextrin aggregates for increasing the solubility of benzimidazoles. Brazilian Journal of Pharmaceutical Sciences, v. 55, 2019. (13/15704-3)