Novel propyl karaya gum nanogels for bosentan: In vitro and in vivo drug delivery performance

• Published in: Colloids and surfaces, B, Biointerfaces B, Biointerfaces, 2019-08, Vol.180, p.263-272
• Main Authors: Laha, Bibek, Das, Sanjib, Maiti, Sabyasachi, Sen, Kalyan Kumar
• Format: Article
• Language: English
• Subjects: Animals; Anti-hypertensive activity; Antihypertensive Agents - administration & dosage; Antihypertensive Agents - pharmacology; Antihypertensive Agents - therapeutic use; Bosentan - administration & dosage; Bosentan - pharmacology; Bosentan - therapeutic use; Calorimetry, Differential Scanning; Disease Models, Animal; Drug Delivery Systems; Drug Liberation; Hypertension - drug therapy; Karaya gum; Karaya Gum - chemical synthesis; Karaya Gum - chemistry; Male; Mice; Nanogels; Nanogels - chemistry; Polyethylene Glycols - chemistry; Polyethyleneimine - chemistry; Polymeric micelles; Propylation; Rats, Wistar; Spectroscopy, Fourier Transform Infrared; X-Ray Diffraction
• ISSN: 0927-7765; 1873-4367
• DOI: 10.1016/j.colsurfb.2019.04.064

[Display omitted] •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.