chondroitin-sulfates and stearylamine

Progress at elimination of malaria is limited by the challenges of reaching large rural population and ensuring patient adherence to adequate pharmacologic treatment. In the present study, a novel material (octadecylamine modified chondroitin sulfate) was synthesized, to fabricate a long acting release meshy gel system as an efficient weapon for protracted warfare to malaria. Ivermectin loaded meshy gels (IVM-MG) composed of different amount of phospholipids, triglyceride and modified chondroitin sulfate were formulated. They were in aqueous state with low viscosity before injection, but rapidly turned into gel state with significantly increased viscosity upon exposure to an aqueous environment after injection. In vitro study proved a sustained released effect in different releasing media. In vivo study showed no irritation at injection site and slowly drug release over a 30-day release period in rat model. Among the three IVM-MG formulations, IVM-MG-3 with the highest amount of octadecylamine modified chondroitin sulfate presented the highest viscosity increase after solution-gel transition, the least initial burst release, and the longest sustained release effect over 30 days in rat model. Furthermore, by using mathematical models, IVM-MG system could boost the efficacy of mass drug administration toward malaria elimination goals. Meshy gel systems for long-acting drug delivery have the potential to revolutionize treatment options for malaria and other diseases of which treatment adherence is essential for their efficacy.

Topics: Amines; Animals; Antimalarials; Chondroitin Sulfates; Culicidae; Delayed-Action Preparations; Drug Carriers; Drug Liberation; Ethanol; Gels; Injections; Insecticides; Ivermectin; Male; Mice; Models, Theoretical; Rats, Wistar; Skin; Viscoelastic Substances; Viscosity

The initial step in mucosal infection by the herpes simplex virus type 2 (HSV-2) requires its binding to certain glycosaminoglycans naturally present on host cell membranes. We took advantage of this interaction to design biomimetic supramolecular hexagonal-shaped nanoassemblies composed of chondroitin sulfate having exalted anti-HSV-2 activity in comparison with native chondroitin sulfate. Nanoassemblies were formed by mixing hydrophobically-modified chondroitin sulfate with α-cyclodextrin in water. Optimization of alkyl chain length grafted on chondroitin sulfate and the ratio between hydrophobically-modified chondroitin sulfate and α-cyclodextrin showed that more cohesive and well-structured nanoassemblies were obtained using higher α-cyclodextrin concentration and longer alkyl chain lengths. A structure-activity relationship was found between anti-HSV-2 activity and the amphiphilic nature of hydrophobically-modified chondroitin sulfate. Also, antiviral activity of hexagonal nanoassemblies against HSV-2 was further improved in comparison with hydrophobically-modified chondroitin sulfate. This work suggests a new biomimetic formulation approach that can be extended to other heparan-sulfate-dependent viruses.

Topics: alpha-Cyclodextrins; Amines; Antiviral Agents; Carbohydrate Conformation; Chemistry, Pharmaceutical; Chondroitin Sulfates; Herpesvirus 2, Human; Hydrophobic and Hydrophilic Interactions; Models, Molecular; Structure-Activity Relationship; Water

Topics: Adhesiveness; Amines; Chemistry, Pharmaceutical; Cholesterol; Chondroitin Sulfates; Collagen Type I; Drug Compounding; Fluorescent Antibody Technique; Gels; Injections, Intra-Arterial; Lipids; Liposomes; Microscopy, Electron, Transmission; Microscopy, Fluorescence; Phosphatidylcholines; Phosphatidylethanolamines; Porosity; Technology, Pharmaceutical