Carbohydrate Nanoparticles: A Novel Drug Delivery Platform for the Systemic Route
Type of DegreeDissertation
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With the phenomenal developments in the fields of biotechnology and molecular biology, the focus in the medical fraternity is shifting towards cellular level intervention. The use of polypeptides, proteins and possibly genes through targeted delivery platforms is viable today. Available particulate delivery platforms are inadequate targeting platforms because of the poor physical and chemical properties of the polymers used. In course of current research a novel nanoparticulate delivery platform has been developed with hydrophilic carbohydrate polymers, using a water-in-oil emulsion and interfacial crosslinking. Synthesis of nanoparticles has been characterized and key parameters affecting the reaction identified. The reaction is dependent on the pH, species of the polymer, the polymer load of the dispersed aqueous phase and species of the crosslinker. Smaller starch polymers were found to be most suitable for this purpose because their relatively higher aqueous solubility and superior rheological properties. Trimesoyl chloride was found to be the best crosslinker because of better reactivity and the higher hydrophilicity imparted to the surface. Sorbitan mono palmitate (Span 40?) was found to be the best surfactant. The nanoparticles have been chemically characterized by determining the degree of substitution (DS). Analytical methodology was developed for quantifying the DS. The reaction occurs in a wide pH range of 3-11 and was base catalyzed at higher and acid catalyzed at lower pHs. The nanoparticles prepared using maltodextrin from amylopectin and trimesoyl chloride had hydrophilic surfaces. The particles suspended in aqueous media as monodispersed mononucleated particles. The crosslinked membrane of the nanoparticles was largely inadequate in sustaining the release of small molecules like tartrazine. For moderate sized proteins like lysozyme though, the membrane was adequate in sustaining the release for weeks. Diffusion based modeling of release data showed two independent modes of release, one fast phase which is complete within 3 hr and one slow phase lasting for weeks. Estimated permeability coefficients show that there is a negative correlation between the degree of substitution and the permeability coefficient of the slower mode of release. Further work is required to establish the behavior of these nanoparticles in vivo. Overall, the developed platform appears suitable for macromolecular delivery in the systemic circulation. Future studies will investigate potential cellular level intervention.