Intravesical mucoadhesive self-emulsifying drug delivery system (SEDDS) have been developed via synthesis and incorporation of S-protected chitosan CS-MNA into SEDDS. N-acetyl cysteine-6-mercaptonicotinamide (NAC-6-MNA) was synthetized via disulphide exchange reaction between N-acetyl cysteine and 6-mercaptonicotinamide dimer. NAC-6-MNA was attached to chitosan (CS) via carbodiimide mediated amide bond formation. The S-protected chitosan (CS-MNA) and chitosan (CS) were complexed with sodium dodecyl sulfate (CS-SDS and CS-MNA-SDS) and incorporated in SEDDS at a concentration of 1% (m/m). SEDDS, SEDDS-CS-SDS and SEDDS-CS-MNA-SDS were characterized regarding size and zeta potential. 6-MNA release from SEDDS-CS-MNA-SDS in presence of glutathione was evaluated. Mucoadhesive properties of these novel formulations were assessed via rheology measurements and residence time evaluation on porcine bladder. Cytotoxicity of formulations was determined on porcine bladder. S-protected chitosan displayed 465.42 ± 75.64 µmol of NAC-6-MNA per gram of polymer. SEDDS and SEDDS-CS-SDS and SEDDS-CS-MNA-SDS displayed a size of 22.5 ± 0.9, 37.4 ± 0.1 and 98.5 ± 5.7 nm at a concentration of 20% (m/v) in simulated urine pH 6.2, and a zeta potential of -5.1 ± 0.2, -1.6 ± 0.1 and -1.4 ± 0.2 mV at a concentration of 1% (m/v) in water at pH 6, respectively. 80% of MNA was released from SEDDS-CS-MNA-SDS in presence of glutathione. Viscosity of SEDDS-CS-SDS/mucus and SEDDS-CS-MNA-SDS/mucus was 6- and 18-fold higher than SEDDS/mucus after 90 min incubation. 2.6%, 5.8% and 14% of SEDDS, SEDDS-CS-SDS and SEDDS-CS-MNA-SDS remained on bladder mucosa within 120 min, respectively. No pronounced bladder cytotoxicity was observed in presence of 0.5% (m/v) formulations. According to these results, SEDDS-CS-MNA-SDS might be a promising carrier for intravesical drug administration.
Keywords: Chitosan; Intravesical drug delivery; Mucoadhesion; Self-emulsifying drug delivery systems; Thiolated chitosan.
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