Purpose: Preparing mucoadhesive nanoparticles (NP) based on quaternary ammonium-chitosan conjugates or their thiolated derivatives, medicated with dexamethasone phosphate (DXP), and studying DXP release from NP and NP mucoadhesivity by a non-invasive 1H-NMR method. Methods: Two structurally different quaternary ammonium-chitosan conjugates, synthesised at 60 °C (N+-Ch(60°)) and 50°C (N+-Ch(50°)), respectively, and their thiolated derivatives (N+-Ch(60°)-SH and N+-Ch(50°)-SH, respectively) were used to prepare DXP medicated NP by ionotropic gelation with hyaluronic acid (HA). Drug release from NP was studied by quantitative NMR (600 MHz, D2O, 25 °C) analyses in the presence or absence of mucin. Translational diffusion coefficients of DXP were measured by Diffusion Ordered SpectroscopY (DOSY) in the presence of each polymer, or mucin, or NP, or NP/mucin or polymer/mucin mixtures. Results: NP were in the 300-400 nm size range. The encapsulation efficiency was in the 20-30% range. DXP was retained for prolonged times by all NP types. Drug release was favoured by the presence of mucin, pointing to NP mucoadhesivity. All NP constituent polymers showed a remarkable affinity for the drug, consistent with the NP drug-retaining ability. Conclusion: An efficient NMR spectroscopic protocol has been developed for measuring drug release from NP and detecting NP mucoadhesivity. The prolonged drug retention within NP suggests that the expected NP internalization by cells of mucous epithelia could create a drug reservoir within the epithelium for a prolonged drug activity.
USING 1H-NMR TO STUDY A NANOPARTICULATE SYSTEM FOR DEXAMETHASONE PHOSPHATE RELEASE AND MUCOADHESIVITY
ZAMBITO, YLENIA;BALZANO, FEDERICA;Angela Fabiano;AIELLO, FEDERICA;UCCELLO BARRETTA, GLORIA
2013-01-01
Abstract
Purpose: Preparing mucoadhesive nanoparticles (NP) based on quaternary ammonium-chitosan conjugates or their thiolated derivatives, medicated with dexamethasone phosphate (DXP), and studying DXP release from NP and NP mucoadhesivity by a non-invasive 1H-NMR method. Methods: Two structurally different quaternary ammonium-chitosan conjugates, synthesised at 60 °C (N+-Ch(60°)) and 50°C (N+-Ch(50°)), respectively, and their thiolated derivatives (N+-Ch(60°)-SH and N+-Ch(50°)-SH, respectively) were used to prepare DXP medicated NP by ionotropic gelation with hyaluronic acid (HA). Drug release from NP was studied by quantitative NMR (600 MHz, D2O, 25 °C) analyses in the presence or absence of mucin. Translational diffusion coefficients of DXP were measured by Diffusion Ordered SpectroscopY (DOSY) in the presence of each polymer, or mucin, or NP, or NP/mucin or polymer/mucin mixtures. Results: NP were in the 300-400 nm size range. The encapsulation efficiency was in the 20-30% range. DXP was retained for prolonged times by all NP types. Drug release was favoured by the presence of mucin, pointing to NP mucoadhesivity. All NP constituent polymers showed a remarkable affinity for the drug, consistent with the NP drug-retaining ability. Conclusion: An efficient NMR spectroscopic protocol has been developed for measuring drug release from NP and detecting NP mucoadhesivity. The prolonged drug retention within NP suggests that the expected NP internalization by cells of mucous epithelia could create a drug reservoir within the epithelium for a prolonged drug activity.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
