NLG anchored niosomal formulation of DOX with enhanced cytotoxicity, internalization and receptor binding potential has implication in targeted cancer therapy.

No abstract

The aim of this study was to develop a nanosuspension of a highly hydrophobic drug, isradipine (ISR) by combination of anti-solvent microprecipitation and high-pressure homogenization to achieve the superior in vitro dissolution and in vivo pharmacokinetic profile. The nanosuspension was formulated using combination of stabilizers as vitamin E TPGS and sodium lauryl sulfate. The developed nanosuspension was characterized for particle size, shape, and zeta potential. The particle size of the developed ISR nanosuspension was observed to be approximately 538 nm (by laser diffraction) and 469 nm (by photon correlation spectroscopy) with -33.3 mV zeta potential. Scanning electron microscopy study revealed the good correlation with particle size measured by photon correlation spectroscopy and laser diffraction. The X-ray diffraction and differential scanning calorimetry showed that ISR was present as an amorphous state in the lyophilized form of nanosuspension. In vitro dissolution and saturation solubility study showed the dissolution rate of nanosuspensions (98.60 %) and saturation solubility (98.76 μg/ml) compared with the coarse drug (11.53 % and 14.1 μg/ml, respectively) had been significantly enhanced. The pharmacokinetic study showed that the nanosuspension exhibits increased in AUC0-48 by 2.0-fold compared to coarse suspension. Further, there was increased in C max and decreased in t max of ISR nanosuspension compared to coarse suspension of ISR. These studies proved that particle size reduction can influence ISR absorption in gastrointestinal tract and thus nanosuspension technology is responsible for enhancing oral bioavailability in rats.

The glucosamine-anchored DOX-loaded targeted niosomes showed its potential in cancer targeted drug therapy with reduced toxicity. Abbreviations ALT alanine transaminase CL clearance CPK creatinine phosphokinase DOX doxorubicin EDC.HCL ethyl carbidimide hydrochloride GLUT glucose transporter GSH glutathione S-transferase LDH lactate dehydrogenase LHRH luteinizing hormone-releasing hormone MDA malonaldehyde NHS N-hydroxy succinimide NLG N-lauryl glucosamine NTAR DoxNio non-targeted doxorubicin niosomes PBS phosphate buffer saline RGD argynyl glycyl aspartic acid SGOT serum glutamate oxaloacetate transaminase SGPT serum glutamate pyruvate transaminase SOD superoxide dismutase TAR DoxNio targeted doxorubicin niosomes Vd volume of distribution.

A novel polymer-drug conjugate, polyethylene glycol-N-(acetyl)-glucosamine-doxorubicin (PEG-NAG-DOX) was evaluated in this study for its in vivo potential for treatment of tumours demonstrating improved efficacy and reduced toxicity. The proposed polymer-drug conjugate comprised of polyethylene glycol-maleimide (mPEG-MAL, 30000 Da) as a carrier, doxorubicin (DOX) as an anticancer drug and N-acetyl glucosamine (NAG) as a targeting moiety as well as penetration enhancer. Doxorubicin has a potent and promising anticancer activity; however, severe cardiotoxicity limits its application in cancer treatment. By modifying DOX in PEG-NAG-DOX prodrug conjugate, we aimed to eliminate this limitation. In vivo anticancer efficacy of the conjugate was evaluated using BDF mice-induced skin melanoma model by i.v. administration of DOX conjugates. Anticancer efficacy studies were done by comparing tumour volume, body weight, organ index and percent survival rate of the animals. Tumour suppression achieved by PEG-NAG-DOX at the cumulative dose of 7.5 mg/kg was two-fold better than that achieved by DOX solution. Also, the survival rate for PEG-NAG-DOX conjugate was >70% as compared to <50% survival rate for DOX solution. In addition, toxicity studies and histopathological studies revealed that while maintaining its cytotoxicity towards tumour cells, PEG-NAG-DOX conjugate showed no toxicities to major organs. Therefore, PEG-NAG-DOX conjugate can be suggested as a desirable candidate for targeted cancer therapy.