Oral In-Situ Nanoplatform with Balanced Hydrophobic-Hydrophilic Property for Transport Across Gastrointestinal Mucosa

被引：2

作者：

Attar, Esha S. ^{[1
]}

Jayakumar, S. ^{[2
,3
]}

Devarajan, Padma V. ^{[1
]}

机构：

[1] Inst Chem Technol, Dept Pharmaceut Sci & Technol, Mumbai 400019, India

[2] Bhabha Atom Res Ctr, Radiat Biol & Hlth Sci Div, Modular Labs, Mumbai 400085, India

[3] Homi Bhabha Natl Inst, Mumbai 400094, India

来源：

AAPS PHARMSCITECH | 2024年 / 25卷 / 05期

关键词：

curcumin; hydrophobic-hydrophilic balance; in-situ approach; lipomer; mucopenetration; transepithelial transport; MUCUS MODULATING AGENTS; DRUG-DELIVERY; CURCUMIN NANOPARTICLES; PROTEIN DRUGS; PARTICLES; OVERCOME; DESIGN; NANOCARRIERS; ABSORPTION; DIFFUSION;

D O I：

10.1208/s12249-024-02824-8

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Transport of oral nanocarriers across the GI epithelium necessitates transport across hydrophilic mucus layer and the hydrophobic epithelium. Based on hydrophobic-hydrophilic balance, Curcumin-Lipomer (lipid-polymer hybrid nanoparticles) comprising hydrophobic stearic acid and hydrophilic Gantrez (TM) AN 119 (Gantrez) were developed, by a radical in-situ approach, to successfully traverse both barriers. A monophasic preconcentrate (Cur-Pre) comprising Cur (Curcumin), stearic acid, Gantrez and stabilizers, prepared by simple solution, was added to an aqueous phase to instantaneously generate Curcumin-Lipomer (Cur-Lipo) of nanosize and high entrapment efficiency (EE). Cur-Lipo size and EE was optimized by Box-Behnken Design. Cur-Lipomers of varying hydrophobic-hydrophilic property obtained by varying the stearic acid: Gantrez ratio exhibited size in the range 200-400 nm, EE > 95% and spherical morphology as seen in the TEM. A decrease in contact angle and in mucus interaction, evident with increase in Gantrez concentration, indicated an inverse corelation with hydrophilicity, while a linear corelation was observed for mucopenetration and hydrophilicity. Cur-SLN (solid lipid nanoparticles) which served as the hydrophobic reference revealed contact angle > 90 degrees, maximum interaction with mucus and minimal mucopenetration. The ex-vivo permeation study through chicken ileum, revealed maximum permeation with Cur-Lipo1 and comparable and significantly lower permeation of Cur-Lipo1-D and Cur-SLN proposing the importance of balancing the hydrophobic-hydrophilic property of the nanoparticles. A 1.78-fold enhancement in flux of hydrophobic Cur-SLN, with no significant change in permeation of the hydrophilic Cur-Lipomers (p > 0.05) following stripping off the mucosal layer was observed. This reiterated the significance of hydrophobic-hydrophilic balance as a promising strategy to design nanoformulations with superior permeation across the GI barrier.

引用

页数：11