Self-assembled polyelectrolyte nanocomplexes between chitosan derivatives and enoxaparin

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Abstract

Polyelectrolyte complexes (PEC) formed from chitosan derivatives and enoxaparin were prepared and parameters influencing complex formation were characterized. Dynamic light scattering (DLS) and laser doppler anemometry (LDA) were used to study the complexation process. Surface morphology of the PECs was observed with atomic force microscopy (AFM). The PEC formation process was influenced by a variety of parameters, including the system pH, polymer/enoxaparin mass ratio, polymer molecular weight, concentration and structure. Soluble complexes in the size range of 200–500 nm with spherical morphology could be obtained at optimized polymer/enoxaparin ratios in the pH range of 3.0–6.5, with positive charge and drug encapsulation efficiency of approximately 90%. An increase in ionic strength of the medium accelerated the dissociation of chitosan/enoxaparin complexes. In contrast, chitosan thiolation, methylation and PEGylation significantly improved the stability of the complexes. Physicochemical properties of the PECs, including particle size, charge density and morphology, could be modified by using different chitosan derivatives. On the basis of our results, we suggest that interactions involved in PEC formation were partly electrostatic in nature, involving the positively charged chitosan derivatives and the negatively charged enoxaparin at pH values in the vicinity of the pKa interval of the two polymers. Oral absorption of the polyelectrolyte nanocomplexes will be studied in vivo.

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