Preparation and Characterization of Simvastatin Nanocapsules: Encapsulation of Hydrophobic Drugs in Calcium Alginate

Abstract

During past few years, development of methods for physical encapsulation of drugs in biocompatible materials in mild conditions for poorly water-soluble hydrophobic drugs which are sensitive to hydrolytic conditions is of high interest in biomedical and pharmaceutical industries. The encapsulation can improve the drug solubility while decreases its side effects besides controlling its pharmacokinetic profile which results in the overall improvement of the therapeutic efficacy. In the current paper, we provide a detailed protocol for encapsulation of poorly water-soluble hydrophobic drugs which is a development of the previously developed protocol of nanocapsule formation by complex formation on the interface of emulsion droplets. The newly developed protocol is based on nanocapsule formation by complex formation on the interface of emulsion droplets except using no organic solvent for potential targeted drug delivery to glioblastoma cells. Simvastatin as a model of hydrophobic drugs of high hydrolytic sensitivity was encapsulated in calcium alginate hydrogel as a biocompatible matrix using the developed protocol. Simvastatin belongs to a group of mevalonate cascade inhibitors (statins) which have recently been considered as a possible new approach in cancer treatment especially glioblastoma. As a cholesterol biosynthesis inhibitor, it is very important to deliver statins only to target cells and not intact cells using targeted drug delivery strategies to avoid dysregulation of cholesterol biosynthesis in normal tissue. To prepare the statin drug nanocarrier’s, the drug was first dissolved in polysorbate 20 nonionic surfactant solution, and then peptide modified calcium alginate was deposited on the micelles interface at neutral pH and 30 °C. The prepared nanocapsules were spherical in shape and very small in size (i.e., 17 ± 5 nm). The drug content of the nanocapsules was 117.3 mg g−1 and the drug loading efficiency for a 5-mg initial amount of the drug was 23.5% ± 3.1%.