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Formulation of insulin-loaded N-trimethyl chitosan microparticles with improved efficacy for inhalation by supercritical fluid assisted atomization.

Abstract：

:Supercritical fluid assisted atomization introduced by a hydrodynamic cavitation mixer (SAA-HCM) was proposed as a green technique to fabricate insulin-loaded dry powders for inhalation administration. N-trimethyl chitosan (TMC), a polymeric mucoadhesive absorption enhancer, was synthesized and successfully micronized from aqueous solution using SAA-HCM. The prepared well-defined spherical TMC microparticles with preserved structure and thermal stability were potential carriers for delivery of proteins. Then, insulin-loaded TMC microparticles with high loading efficiency were coprecipitated from aqueous solutions using SAA-HCM without use of any organic solvents. The polymer/protein ratio revealed to be a factor influencing the particle morphology, and non-coalescing composite microparticles in amorphous state mainly ranging from 1μm to 5μm could be obtained in this work. Aerodynamic properties were assessed by next generation impactor (NGI) and the mass median aerodynamic diameter (MMAD) lied inside the inhalable range of 1-5μm, while fine particle fraction (FPF) reached above 60%. The structural integrity of encapsulated insulin was confirmed by HPLC, circular dichroism and fluorescence spectroscopy. In vivo study demonstrated that TMC could enhance the absorption and bioavailability of the pulmonarily administered insulin formulation for SD rats. These results suggest that TMC microparticles could be efficiently prepared as a promising vehicle for drug delivery, and SAA-HCM is a promising technique to prepare inhalable polymer/protein composite dry powders.

journal_name

Int J Pharm

journal_title

International journal of pharmaceutics

authors

Shen YB,Du Z,Tang C,Guan YX,Yao SJ

doi

10.1016/j.ijpharm.2016.03.053

subject

Has Abstract

pub_date

2016-05-30 00:00:00

pages

223-33

issue

1-2

eissn

0378-5173

issn

1873-3476

pii

S0378-5173(16)30262-9

journal_volume

505

pub_type

杂志文章

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