학술논문
Novel propyl karaya gum nanogels for bosentan: In vitro and in vivo drug delivery performance.
Document Type
Article
Source
Subject
*NANOGELS
*DRUG solubility
*COLLOIDS
*PROPYL group
*PERMUTATION groups
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Language
ISSN
0927-7765
Abstract
• Propylation of karaya gum led to the formation of self-assembled nanogels in water. • Low CAC and high zeta potential indicated physical stability of nanogels. • Core-shell nanogels accommodated more than 85% bosentan in hydrophobic core. • Nanogels exhibited pH-sensitive drug release behavior in simulated bio-fluids. • Pre-clinical testing demonstrated prolonged anti-hypertensive activity. The amphiphilic propyl Karaya gum (KG) with a degree of propyl group substitution of 3.24 was synthesized to design self-assembled nanogels as carriers for bosentan monohydrate, a poorly soluble antihypertensive drug. The drug was physically hosted into the hydrophobic core of the micellar nanogels by solvent evaporation method. TEM images revealed spherical shape and core-shell morphology of the nanogels. Depending upon polymer: drug weight ratio, the drug entrapment efficiency of >85% was attained. The carriers had hydrodynamic diameter in the range of 230–305 nm with narrow size distribution. The zeta potential of −23.0 to −24.9 mV and low critical association concentration (CAC) of 8.32 mg/l provided evidence that the colloidal nanogel system was physically stable. Thermodynamics of the propyl KG system in water favored spontaneous self-assembly of propyl KG. FTIR, thermal and x-ray analyses suggested that the drug was compatible in the hydrophobic confines of the nanogels. The micellar nanogels liberated their contents in simulated gastrointestinal condition in a pH-dependent manner over a period of 10 h. Peppas-Sahlin modeling of in vitro drug release data suggested that the polymer relaxation/swelling mechanism dominated the drug release process. Pre-clinical testing of the mucoadhesive nanogel formulations exhibited that the system could monitor the anti-hypertensive activity for a prolonged period. Overall, this propyl KG micellar nanogel system had a great potential and splendid outlook to serve as novel oral controlled release carriers for poorly soluble drugs with outstanding pharmacodynamics. [ABSTRACT FROM AUTHOR]