Polymer-lipid hybrid nanoparticles as enhanced indomethacin delivery systems

Abstract

Non-steroidal anti-inflammatory drugs (NSAIDs), i.e. indomethacin used for rheumatoid arthritis and non-rheumatoid inflammatory diseases, are known for their injurious actions on the gastrointestinal (GI) tract. Mucosal damage can be avoided by using nanoscale systems composed by a combination of liposomes and biodegradable natural polymer, i.e. chitosan, for enhancing drug activity. Aim of this study was to prepare chitosan-lipid hybrid delivery systems for indomethacin dosage through a novel continuous method based on microfluidic principles. The drop-wise conventional method was also applied in order to investigate the effect of the two polymeric coverage processes on the nanostructures features and their interactions with indomethacin. Thermal-physical properties, mucoadhesiveness, drug entrapment efficiency, in vitro release behavior in simulated GI fluids and stability in stocking conditions were assayed and compared, respectively, for the uncoated and chitosan-coated nanoliposomes prepared by the two introduced methods. The prepared chitosan-lipid hybrid structures, with nanometric size, have shown high indomethacin loading (about 10%) and drug encapsulation efficiency up to 99%. TEM investigation has highlighted that the developed novel simil-microfluidic method is able to put a polymeric layer, surrounding indomethacin loaded nanoliposomes, thicker and smoother than that achievable by the drop-wise method, improving their storage stability. Finally, double pH tests have confirmed that the chitosan-lipid hybrid nanostructures have a gastro retentive behavior in simulated gastric and intestinal fluids thus can be used as delivery systems for the oral-controlled release of indomethacin. Based on the present results, the simil-microfluidic method, working with large volumes, in a rapid manner, without the use of drastic conditions and with a precise control over the covering process, seems to be the most promising method for the production of suitable indomethacin delivery system, with a great potential in industrial manufacturing.

Keywords: Chitosan; Chitosan (CAS n. 9012-76-4, PubChem CID: 71853); Cholesterol (PubChem CID: 5997); Drug delivery; Glacial acetic acid (CAS n. 64-19-7, PubChem CID: 176); Indomethacin; Indomethacin (CAS n. 53-86-1, PubChem CID: 3715); L-α-Phosphatidylcholine (PC) from soybean (CAS n. 8002-43-5, PubChem CID: 122218); Liposome; Nano-encapsulation; Simil-microfluidic technique; TEM.