Journal of Pharmaceutical and Biopharmaceutical Research

The drug release rates of poorly soluble medications such as doxorubicin has been investigated in this paper. Since the drug was fixed, different carriers used to deliver it and their release rates compiled from literature were evaluated in this paper. Even though targeting of drugs is very important in drug delivery, it is not within the scope of this paper. However, functionalization of the carrier may provide this benefit, those constructs are included for comparison in terms of hybrid constructs. Dendrimer, micelles and hybrid constructs used in the delivery of doxorubicin compared in this paper with respect to carrier size and drug loading. Assuming that the dissolution follows a slow release, 40-50% of the drug in the phase I representing a sudden or the burst release, followed by a steady release of 50-60% of the drug in phase II, not all the carriers and their sizes exhibited this behavior. Carriers and hybrid constructs 38nm size were more effective where phases I and II observed, however, as the size decreased to 34 nm or increased above 40nm, minimal release occurred meaning the carriers were too big to penetrate the vasculature permeability. Nano-carriers, dendrimers, micelle, hybrid dendrimers and micelles were found to be effective with the carrier manufacturing, generation, polymer, molecular weight of the carrier and other parameters. The release rate of doxorubicin was found to be effective with dendrimers together with hybrid dendrimer exhibiting a bilinear behavior. Micelles 20nm were more effective representing 60% of release in 10 hours followed by additional 25% in 35 hours exhibiting a bilinear behavior. Size greater than 20nm resulted in slow release reaching less than 10 to 40% of drug. Several drugs exhibited multiple slopes in their kinetics when micelle was used. The therapeutic efficacy of hybrid micelle was superior to other nano-carriers.

Diabetic complications are mostly due to hyperglycemia. Hyperglycemia is reported to be associated with oxidative stress. It can result in changes in the activities of drug-metabolizing enzymes and membrane-integrated transporters, which can modify the fate of drugs and other xenobiotics. An in vivo intestinal perfusion model was used to investigate how experimental hyperglycemia affects intestinal elimination and biliary excretion of ibuprofen enantiomers in the rat. Experimental diabetes was induced by intravenous (i.v.) administration of streptozotocin. The intestinal perfusion medium contained 250 µM racemic ibuprofen. A validated isocratic chiral HPLC method with UV detection was developed to determine the amount of the two enantiomers in the intestinal perfusate and the bile. The results indicated that experimental diabetes doesn’t cause a statistically significant difference in the disappearance of ibuprofen enantiomers from the small intestine. Analysis of the bile samples detected only the (S)-IBP enantiomer. Excretion of the ibuprofen enantiomer to the bile decreased in experimental diabetes. The observed changes can affect the pharmacokinetics of drugs administered in hyperglycemic individuals.