Functional benefits of PLGA particulates carrying VEGF and CoQ10 in an animal of myocardial ischemia

Myocardial ischemia (MI) remains one of the leading causes of death worldwide. Angiogenic therapy with the vascular endothelial growth factor (VEGF) is a promising strategy to overcome hypoxia and its consequences. However, from the clinical data it is clear that fulfillment of the potential of VEGF warrants a better delivery strategy. On the other hand, the compelling evidences of the role of oxidative stress in diseases like MI encourage the use of antioxidant agents. Coenzyme Q10 (CoQ10) due to its role in the electron transport chain in the mitochondria seems to be a good candidate to manage MI but is associated with poor biopharmaceutical properties seeking better delivery approaches. The female Sprague Dawley rats were induced MI and were followed up with VEGF microparticles intramyocardially and CoQ10 nanoparticles orally or their combination with appropriate controls. Cardiac function was assessed by measuring ejection fraction before and after three months of therapy. Results demonstrate significant improvement in the ejection fraction after three months with both treatment forms individually; however the combination therapy failed to offer any synergism. In conclusion, VEGF microparticles and CoQ10 nanoparticles can be considered as promising strategies for managing MI

High-performance liquid chromatographic analysis of amphotericin B in rat plasma using α-naphthol as an internal standard

A simple, sensitive and accurate reverse phase high-performance liquid chromatographic (RP-HPLC) method with photo-diode array detector (PDA) was developed and validated for the determination of amphotericin B (AMB) in the rat plasma using a new internal standard (IS) α-naphthol. The plasma samples were subjected to protein precipitation with methanol prior to a HPLC analysis. Chromatographic separations were achieved on a Nucleosil® 100-5C18 (150 mm × 4.6 mm) column. The mobile phase consisted of acetonitrile and sodium acetate buffer (pH 4; 10 mM) in a gradient mode. Detection was carried out at a wavelength of 407 and 294 nm for AMB and IS, respectively. The retention times of AMB and IS were about 6.8 and 7.8 min, respectively. The calibration curve was linear in the range of 10-2000 ng mL−1 for AMB (r2 > 0.998). No significant matrix effect was observed on quantification of AMB or IS. At three quality control concentrations of 20, 500, and 2000 ng mL−1, the intra-day and inter-day relative standard deviation ranged from 1.13% to 4.91%. The limit of detection (LOD) was 5 ng mL−1 and the limit of quantification (LOQ) was 10 ng mL−1 for AMB in rat plasma. This method is simple, sensitive, rapid and does not require any extensive sample purification before injecting into HPLC

Evaluating the potential of polyester nanoparticles for per oral delivery of amphotericin B in treating visceral leishmaniasis

Leishmaniasis is a protozoan disease, which is responsible for response for major epidemics in many parts of the World. Amphotericin B (AMB) is one of the drugs used to treat leishmaniasis but it must be given intravenously and serious side effects such as nephrotoxicity can limit its use. Development of a formulation of AMB, which can be given by a non-invasive route but is still as effective as the conventional formulation, whilst causing minimal adverse side effects, is required. The present study describes a method for scale up production of a per oral nanoparticle formulation of AMB (AMB-NP) and compared its efficacy both in vitro and in vivo against Leishmania donovavni. Prophylactic studies showed that the AMB-NP formulation was significantly more effective (p < 0.05) than the same dose of AMB solution at suppressing parasite numbers compared to controls in bone marrow derived macrophages infected with L. donovani. Per oral treatment with AMB-NP resulted in a significant reduction in liver parasite burdens (p < 0.05) compared to control values and the formulation had a similar antileishmanial activity against parasites with different inherent susceptibilities to sodium stibogluconate

PLGA nanoparticles for oral delivery of hydrophobic drugs: influence of organic solvent on nanoparticle formation and release behavior in vitro and in vivo using estradiol as a model drug

The aim of present investigation was to screen different solvents for optimizing nanoparticle preparation in terms of particle size, entrapment efficiency, and finally, release behavior using a model drug estradiol. Nanoparticles were prepared following emulsion-diffusion-evaporation method using didodecyldimethyl ammonium bromide (DMAB) or polyvinyl alcohol (PVA) as stabilizers. Ethyl acetate (EA), acetone (ACE), chloroform (CHL), and dichloromethane (DCM) were used as organic solvents either individually or in combinations. DMAB when used as surfactant led to smaller particle size as compared to PVA irrespective of the solvents and combinations used, but on the other hand, PVA produced particles with higher entrapment when combinations of solvents used. DCM in combination with EA resulted in highest entrapment with both the stabilizers. All the formulations exhibited similar in vitro release profile (Zero order) irrespective of stabilizer (DMAB or PVA) used, however, the average release per day was higher in case of DCM formulations due to greater entrapment. In situ uptake studies suggest that smaller the particle size better is the uptake. The bioavailability from nanoparticles was assessed in male Sprague Dawley (SD) rats at a dose of 1 mg drug/rat. EA/DMAB (size 116.0 ± 2.6 nm) and DCM:EA 70:30/DMAB (size 253.0 ± 5.5 nm) showed the release for 9 and 5 days, respectively, whereas EA/PVA (size 279.3 ± 2.5 nm) released the drug over the periods of 3 days suggesting that particle size has significant role in determining the fate of nanoparticles in vivo. Histopathological examination revealed absence of any inflammatory response with the formulations under the studied period