pH Responsive Polysaccharide vesicles for drug delivery

Abstract

This thesis emphasizes on the design and synthesis of pH responsive amphiphiles based on biodegradable dextran as hydrophilic segment and different hydrophobic units. In this work, the role of hydrophobic part in the molecular self-assembly of amphiphiles into vesicles were studied in detail by using linear, branched and aromatic long chains as hydrophobic segments. The newly synthesized amphiphiles were characterized by NMR and FT-IR technique. Self-assembly of these amphiphiles in aqueous medium was investigated using FE-SEM and dynamic light scattering (DLS) techniques. From the self-assembly studies, it was inferred that only the amphiphile having pentadecylphenol (PDP) as a pendant group (i.e. Dex-PDP-IM) self-organized to form vesicles of 190 nm diameter. While, other amphiphilic dextran derivatives self-assembled to form nanoparticles of 140-170 nm. Further, the loading efficiency of these scaffolds were evaluated by using three different dyes; Rhodamine B (hydrophilic dye), Nile Red and Pyrene (hydrophobic dyes). Dex-PDP-IM based vesicle successfully encapsulated both hydrophilic and hydrophobic dyes independently. Additionally, these dextran vesicles exhibited dual drug loading phenomena. In other words, simultaneously both Rh B and pyrene were efficiently loaded in to the dextran based vesicular scaffold. Pyrene gets localized in the hydrophobic layer, while Rh B in the inner aqueous interior of the vesicle. The release kinetics of Rh B encapsulated Dex-PDP-IM was investigated at pH 7.4 (physiological pH), 5.5 (endosomal pH) and 2 (extreme acidic condition). Acidic pH was employed as the stimuli since the nanoscaffold is having an imine linkage, which is acid labile. At physiological pH, around 45-50% of the dye was retained in the vesicle. On the other hand, at lower pH i.e. 5.5 almost 80% of the dye gets released due to hydrolysis of imine linkage and at pH = 2, 100% of the dye leaches out from the vesicle. Thus the tailor made Dex-PDP-IM is a highly potent nanocarrier to delivering both hydrophobic as well as hydrophilic anticancer drug to the targeted tumor tissues.