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Formulation Design and Preclinical Evaluations of Surface Modified Lipid Nanoparticles-Coupled Gel Encapsulating Dihydroartemisinin for Treatment of Localized Inflammation

Previously, it has been claimed that artemisinin derivatives, e.g., dihydroartemisinin, possess very potent anti-inflammatory activity. The study aimed to formulate gels based on surface-modified nanostructured lipid carrier (NLC) and contain dihydroartemisinin (DHA) to treat localized inflammation. NLC was developed using Softisan®154 and Tetracarpidium conophorum oil and structured using PEG 4000. Physicochemical characterization of NLC, including surface charge, particle size, and encapsulation efficiency (EE%), was evaluated. NLCwas dispersed in hydroxypropyl cellulose, and the resulting nanogels were evaluated for drug content, ex vivo permeation, and anti-inflammatory activity. The surface charge and particle size of NLC ranged from -15.3 ± 1.1 to -25.5 ± 2.1 mV and 85.5 ± 8.6 – 108.7 ± 5.5 nm respectively. EE% of NLC was in the range of 90.0 ± 1.21 – 99.3 ± 1.60 %. NLC gels had high drug content (83 – 99 %). Ex vivo permeation study showed sustained-release of DHA over 24 h. The gels produced a sustained-release reduction of egg albumin-induced inflammation in rats up to 8 h for 7 days. Development of surface-modified lipid nanoparticles-based gel containing DHA produced controlled release of the drug localized inflammation.