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Improvement in dissolution rate and photodynamic efficacy of chlorin e6 by sucrose esters as drug carrier in nanosuspension formulation: optimisation and in vitro characterisation.
Journal of Pharmacy and Pharmacology 2018 September
OBJECTIVES: Chlorin e6 is a poorly water-soluble photoactive drug. Its monomers form aggregates at the tumour physiological pH, which drastically reduces its photodynamic efficacy. This study aimed to improve the dissolution rate and photodynamic efficacy of chlorin e6 by nanosuspension formulation using biodegradable sucrose esters as drug carrier.
METHODS: A modified emulsion-solvent diffusion method was used to prepare the nanosuspension, where amount of Ce6, ratio of sucrose monopalmitate to sucrose monolaurate as carrier and ratio of dichloromethane to acetone as solvent, were varied using central composite design. Particle size, zeta potential, encapsulation efficiency and in vitro drug release characteristics of the nanosuspensions were evaluated. The formulation was optimised by response surface methodology and its photodynamic efficacy evaluated.
KEY FINDINGS: The optimised nanosuspension had mean particle size of ~200 nm, 88% drug encapsulation efficiency and faster drug release compared to pure Ce6. Spectroscopic studies showed that Ce6 exists in monomeric form in the carrier, which facilitated a remarkable increase in cellular uptake, in vitro singlet oxygen generation and cytotoxicity to oral squamous carcinoma cells.
CONCLUSIONS: The dissolution rate and photodynamic efficacy of Ce6 were markedly improved by formulating the drug as a nanosuspension with sucrose esters as drug carrier.
METHODS: A modified emulsion-solvent diffusion method was used to prepare the nanosuspension, where amount of Ce6, ratio of sucrose monopalmitate to sucrose monolaurate as carrier and ratio of dichloromethane to acetone as solvent, were varied using central composite design. Particle size, zeta potential, encapsulation efficiency and in vitro drug release characteristics of the nanosuspensions were evaluated. The formulation was optimised by response surface methodology and its photodynamic efficacy evaluated.
KEY FINDINGS: The optimised nanosuspension had mean particle size of ~200 nm, 88% drug encapsulation efficiency and faster drug release compared to pure Ce6. Spectroscopic studies showed that Ce6 exists in monomeric form in the carrier, which facilitated a remarkable increase in cellular uptake, in vitro singlet oxygen generation and cytotoxicity to oral squamous carcinoma cells.
CONCLUSIONS: The dissolution rate and photodynamic efficacy of Ce6 were markedly improved by formulating the drug as a nanosuspension with sucrose esters as drug carrier.
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