Polymer relationships during preparation of chitosan-alginate and poly-l-lysine-alginate nanospheres

The preparation of chitosan-alginate nanospheres is described and their properties compared to the poly-L-lysine-alginate system. The mass ratio range of sodium alginate:CaCl(2):cationic polymer (poly-L-lysine [PLL] or chitosan) to prepare nanospheres was 100:17:10. This mass ratio ensured that the calcium alginate was maintained in the pre-gel phase and sufficient cationic polymer was present to form nanospheres. At low cationic polymer concentrations, nanospheres were not formed, whereas microspheres were formed at higher concentrations. The release of entrapped methylene blue from the nanospheres was directly proportional (R(2)=0.98) to the sodium chloride concentration in the dissolution medium. The sodium ions more efficiently displace PLL compared to chitosan; hence, the mass of drug released from the chitosan-alginate nanospheres is slow for equivalent sodium ion concentration. Isothermal titration calorimetry studies determined that the primary binding affinity between calcium and alginate was 1.33 x 10(6)/mole and entropically driven, whereas, the second binding affinity was weaker (1.03 x 10(4)/mole) and driven by both enthalpy and entropy. This binding was competitively inhibited by sodium ions. Similarly, the binding of PLL to calcium alginate pre-gel was electrostatic and competitively inhibited by sodium, although, the thermodynamic parameters for this interaction could not be determined.