Synthesis and characterization of polymeric prodrug conjugate systems based on poly (p-hydroxystyrene): In vitro hydrolysis behavior and antibacterial activity

Abstract

The synthesis and in-vitro evaluation of a novel polymeric systems based on linear poly(p-hydroxystyrene) for targeted controlled release have been described. Linear poly(p-hydroxystyrene) (PHS) functionalized with chloroacetyl groups was first prepared by reacting PHS with chloroacetyl chloride, in presence of pyridine as a catalyst, with degree of chloroacetylation ranged from 87 to 96 mol%. The resulting chloroacetylated-PHS (CPHS) was then coupled with each of sodium diclofenac and 1,3-diaminopropane affording the corresponding polymers P1 and P3, respectively, in quantitative loading yields. Their structures were confirmed by means of FTIR, 1 H-NMR as well as by elemental analysis. The hydrolysis in the heterogeneous system of CPHS-diclofenac conjugate was performed in buffer solutions (pH 1.2 ,7.4 and 9) at 37 o C by UV spectroscopy at the absorption wavelength of diclofenac sodium ( max = 276 nm). The drug could be released by selective hydrolysis of the ester bond at the side of the drug moiety. The hydrolytic behavior was found to be mainly dependant on the pH value of the hydrolysis medium. The obtained results suggested that this polymer could be useful in controlled release systems after in-vivo examinations. The antibacterial activities of the modified polymers were also tested against Staphylococcus aureus, Enterococcus, Escherichia coli, Pseudomonas aeruginosa, Salmonella typhi, and Klebsiella pneumoniae. They showed good antibacterial activity which differed according to the concentration of the polymer as obtained from minimum inhibitory concentration (MIC) studies