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

• Published in: AAPS PharmSciTech Vol. 25; no. 5; p. 113
• Main Authors: Attar, Esha S., Jayakumar, S., Devarajan, Padma V.
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 15.05.2024
• Subjects: Administration, Oral; Animals; Biochemistry; Biological Transport - physiology; Biomedical and Life Sciences; Biomedicine; Biotechnology; Curcumin - administration & dosage; Curcumin - chemistry; Curcumin - pharmacokinetics; Drug Carriers - chemistry; Hydrophobic and Hydrophilic Interactions; Intestinal Mucosa - metabolism; Lipids - chemistry; Nanoparticles - chemistry; Particle Size; Pharmacology/Toxicology; Pharmacy; Polymers - chemistry; Polyvinyls - chemistry; Research Article; Stearic Acids - chemistry; transepithelial transport; lipomer; hydrophobic-hydrophilic balance; approach; mucopenetration; curcumin; in-situ approach
• DOI: 10.1208/s12249-024-02824-8
• ISSN: 1530-9932

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™ 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°, 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. Graphical Abstract