Controlled release starch-lipid implant for the therapy of severe malaria

Parenteral depot systems can provide a constant release of drugs over a few days to months. Poly-(lactic acid) (PLA) and Poly-(lactide-co-glycolide) (PLGA) are the most commonly used polymers in the production of these systems. Finding alternatives to these polymers is of great importance to avoid certain drawbacks of these polymers (e.g. microacidity) and to increase the selection possibilities. In this study, different types of starch in combination with glycerol monostearate (GMS) were developed and investigated for their physicochemical properties and release characteristics. The noninvasive method of electron paramagnetic resonance (EPR) was used to study the release kinetics and mechanisms of nitroxide model drugs. The studies demonstrated the general suitability of the system composed of high amylose starch and GMS to form a controlled release system. For further characterization of the prepared system, formulations with different proportions of starch and GMS, loaded with the antimalarial agents artesunate or artemether were prepared. The implants were characterized with X-ray powder diffraction (XRPD) and texture analysis. The in vitro release studies demonstrated the sustained release of artemether over 6 days from a starch-based implant which matches desired kinetic for the treatment of severe malaria. In summary, a starch-based implant with appropriate mechanical properties was produced that can be a potential candidate for the treatment of severe malaria.

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Materials

Native pea starch (PEA STARCH N-735) and high amylose starch (MAIZE STARCH AMYLO N-400 (amylose content ≈53%)) were kindly provided by Roquette (Lestrem, France). Hydroxyethyl starch (HES) was kindly provided by Serumwerk Bernburg (Bernburg, Deutschland). Glycerol monostearate (Kolliwax® GMS II) was kindly provided by BASF (Germany). Glycerol monostearate (IMWITOR® 491) was kindly provided by IOI Oleo GmbH (Germany). Tempol (4-Hydroxy-TEMPO) and Tempol Benzoate (4-hydroxy-tempo benzoate) were purchased from SIGMA Aldrich Chemie GmbH (Munich, Germany). Artemether and artesunate were purchased from abcr GmbH. Olive oil was purchased from Caelo (Germany). NMP (1-Methyl-2-pyrrolidone) was purchased from Sigma-Aldrich (USA). Testing media was Phosphate Buffered Saline (Ph.Eur.) plus 1% sodium dodecyl sulfate (SDS), adjusted to pH 7.4. SDS was purchased from Sigma Aldrich Chemie GmbH (Munich, Germany). Acetonitrile (VWR International, Darmstadt, Germany), Formic Acid (Merck, Germany) and, double distilled water were used for the HPLC measurements.

Golbarg Esfahani, Olaf Häusler, Karsten Mäder,
Controlled release starch-lipid implant for the therapy of severe malaria,
International Journal of Pharmaceutics, Volume 622, 2022, 121879, ISSN 0378-5173,
https://doi.org/10.1016/j.ijpharm.2022.121879.