Abstract
Poor drugability problems are commonly seen in a class of chemical entities with poor solubility in water and oil, and moreover, physicochemical instability of these compounds poses extra challenges in design of dosage forms. Such problems contribute a significant high failure rate in new drug development. A hybrid nanoparicle-in-oil-in-water (N/O/W) submicron emulsion was proposed for improved delivery of poorly soluble and unstable drugs (e.g., dihydroartemisinin (DHA)). DHA is known for its potent antimalarial effect and antitumor activity. However, its insolubility and instability impose big challenges for formulations, and so far, no injectable dosage forms are clinically available yet. Therefore, an injectable DHA N/O/W system was developed. Unlike other widely-explored systems (e.g., liposomes, micelles, and emulsions), in which low drug load and only short-term storage are often found, the hybrid submicron emulsion possesses three-fold higher drug-loading capacity than the conventional O/W emulsion. Of note, it can be manufactured into a freeze-drying form and can render its storage up to 6 months even in room temperature. The in vivo studies demonstrated that the PK profiles were significantly improved, and this injectable system was effective in suppressing tumor growth. The strategy provides a useful solution to effective delivery of such a class of drugs.
Highlights
Poor solubility of a chemical entity is a major obstacle affecting its drugability [1]
Drugs were incorporated into solid lipid nanoparticles (SLN) and dispersed in oil as oily phase, and the oily phase was used to dispersed in aqueous solution with homogenization for preparation of the N/O/W submicron emulsion (Figure 1)
The drug-loading capacity was improved by the DHA N/O/W emulsion, in which DHA concentration
Summary
Poor solubility of a chemical entity is a major obstacle affecting its drugability [1]. It is estimated that more than 40% of the new chemical entities generated in drug discovery programs are poorly soluble [2]. With growing interest in the role of modern pharmaceutics in early stage of drug discovery and development, rationale design of drug delivery systems for poorly soluble drugs has been widely explored, such as emulsions [3,4], solid lipid nanoparticles [5,6], micelles, and liposomes [7,8]. For we propose a novel hybrid system of the nanoparticle-in-oil-in-water (N/O/W) submicron emulsion. Considering the oil compatibility, solid lipid nanoparticles (SLN) were selected. Drugs were incorporated into SLN and dispersed in oil as oily phase, and the oily phase was used to dispersed in aqueous solution with homogenization for preparation of the N/O/W submicron emulsion (Figure 1)
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