Impacts of dextran sulfate’s chain length on the characteristics of its self-assembled colloidal complex formed with amphiphilic small-molecule drug

Abstract

Self-assembled colloidal complexes of dextran sulfate (DXT) and amphiphilic small-molecule drugs have recently emerged as an attractive drug formulation strategy to improve drug delivery efficacy. Herein we investigated the effects of DXT’s chain length (MW=5kDa and 500kDa) on the (1) physical characteristics (i.e. size, zeta potential, drug payload, colloidal stability), (2) preparation efficiency, and (3) dissolution characteristics of the colloidal complexes produced. Antibiotic ciprofloxacin (CIP) was used as the model amphiphilic drug. Compared to its low MW DXT counterpart, the use of high MW DXT resulted in colloidal complex having (1) smaller size, (2) lower CIP payload, (3) higher production yield; while exhibiting similar CIP utilization rate, zeta potential, colloidal stability, and dissolution characteristics. The use of long-chain DXT was believed to increase the occurrence of inter-DXT chain interactions in CIP-DXT complexation causing earlier phase transition of the soluble complex to its insoluble form, resulting in the smaller size and lower payload. Furthermore, the effects of two key variables in drug-polysaccharide complexation, i.e. pH and charge ratio of CIP to DXT (RCIP/DXT), were investigated, from which both colloidal complexes were found to share fairly similar optimal preparation conditions (i.e. acidic pH and RCIP/DXT slightly above unity).