Shahid Jamil

Enhanced oral bioavailability of insulin-loaded solid lipid nanoparticles: pharmacokinetic bioavailability of insulin-loaded solid lipid nanoparticles in diabetic rats.

Abstract Objective: Insulin is a hormone used in the treatment of diabetes mellitus. Multiple injections of insulin every day may causes pain, allergic reactions at injection site, which lead to low patient compliance. The aim of this work was to develop and evaluate an efficient solid lipid nanoparticle (SLN) carrier for oral delivery of insulin. Methods: SLNs were prepared by double emulsion solvent evaporation (w/o/w) technique, employing glyceryltrimyristate (Dynasan 114) as lipid phase and soy lecithin and polyvinyl alcohol as primary and secondary emulsifier, respectively, and evaluated in vitro for particle size, polydispersity index (PDI) and drug entrapment. Results: Among the eight different developed formulae (F1–F8), F7 showed an average particle size (99 nm), PDI (0.021), high entrapment of drug (56.5%). The optimized formulation (F7) was further evaluated by FT-IR, DSC, XRD, in vitro release, permeation, stability, bioavailability and pharmacological studies. Insulin-loaded SLNs showed better protection from gastrointestinal environment as evident from the relative bioavailability, which was enhanced five times as compared to the insulin solution. A significant enhancement of relative bioavailability of insulin was observed, i.e. approximately five times of pure insulin solution when loaded in SLN (8.26% versus 1.7% only).

Effect of Black Seed on Dextromethorphan O- and N-Demethylation in Human Liver Microsomes and Healthy Human Subjects

OBJECTIVE To investigate the effects of black seed on the metabolic activities of CYP3A4 and CYP2D6 in human liver microsomes and in human subjects using dextromethorphan as a probe drug. METHODS CYP2D6-mediated O-demethylation and CYP3A4-mediated N-demethylation of dextromethorphan (DEX) to dextrorphan (DOR) and 3-methoxymorphinan (3-MM), respectively, were utilized to assess the metabolic activities of the two enzymatic pathways. In the in vitro experiments, DEX was incubated with microsomes and NADPH in absence or presence of black seed extract (10-100 microg/ml) and the formation of the metabolites were measured by HPLC. In the clinical study, four healthy volunteers received a single oral dose of DEX 30 mg alone in phase I, and along with last dose of black seed (2.5 g twice daily for seven days) in phase II. Activities of the two enzymes were evaluated based on the urinary metabolic ratios (MRs), which were calculated from eight-hour urine collections. DEX and its metabolites were assayed in urine samples by HPLC following a liquid-liquid extraction. RESULTS Black seed extracts significantly inhibited the formation of both metabolites in microsomes. The maximum inhibition was observed at the highest extract concentration (i.e., 100 microg/ml), which was about 80% and 60% for DOR and 3-MM, respectively. In the clinical study, the urinary MRs of DEX/DOR and DEX/3-MM increased by factors of 127 and 1.6-fold, respectively, after consumption of black seed. CONCLUSION Black seed significantly inhibited CYP2D6 and CYP3A4 mediated metabolism of DEX in human liver microsomes and healthy human volunteers indicating that it has the potential to interact with CYP2D6 and CYP3A4 substrates.

Development and evaluation of PLGA polymer based nanoparticles of quercetin

Quercetin is the most abundant antioxidant found in the human diet. Low aqueous solubility of quercetin limits its bioavailability and hence therapeutic effects. Therefore, the aim of the present study was to develop a poly lactide-co-glycolic acid (PLGA) polymer based nanoparticles of quercetin with a view to improve its aqueous solubility and examine the effect on its antioxidant and diuretic properties. Nanoparticles of quercetin were developed by single emulsion-solvent evaporation technique and evaluated in vitro for differential scanning calorimetry (DSC), Fourier transforms infra-red (FTIR) spectroscopy, particle size, polydispersity index and drug entrapment efficiency. Among the five different formulations (F1, F2, F3, F4 and F5), F2 and F3 were optimized with an average particle size of 189nm and 186nm and high entrapment values of 86.48%, 83.71%, respectively. SEM images of confirmed that prepared nanoparticles were spherical in shape with a smooth surface. In vitro release and anti-oxidant activity confirmed significant results. Furthermore, its in vivo diuretic activity was much better as compared to pure quercetin. The overall results suggest that PLGA polymer based nanoparticle could be a potential option for quercetin delivery.

Development and evaluation of olmesartan medoxomil loaded PLGA nanoparticles

The purpose of the present study was to develop olmesartan medoxomil (OLM) loaded poly (d,l-lactide-co-glycolide) (PLGA) nanoparticles by nanoprecipitation technique. Olmesartan medoxomil nanoparticles (F1–F3) were prepared using PLGA as polymer and Pluronic acid 127 as a surfactant. Developed PLGA nanoparticles were evaluated for particle size, polydispersity index (PI), differential scanning calorimetry (DSC), Fourier transforms infrared (FTIR) spectroscopy, powder X-ray diffraction (XRD), scanning electron microscopy (SEM), drug entrapment efficiency (EE%) and in vitro drug release. Optimised PLGA nanoparticle (F3) had particle size of 97.8 ± 6.3 nm, EE of 58.33% and drug release of 37.1% after 24 h of study. SEM images confirmed that developed nanoparticles were spherical in shape with a smooth surface. DSC, FTIR, and XRD spectra indicated formation of PLGA nanoparticles. The results suggest that PLGA polymer-based nanoparticle could be a potential option for sustained drug delivery of OLM.

RP-HPLC Method for the Analysis of Quercetin in Eruca Sativa with Green Solvent

Background: Quercetin is a major representative of flavonolsub-classs of flavonoids which has a nutritional value and active moieties of many medicinal plants with potent antioxidant, Antidiabetic, anti-tumor, antiviral and anti-inflammatory properties. Eruca Sativa one of the most consumable herbs in Saudi Arabia, has not been analyzed yet by using green solvent. Objectives: A simple, sensitive, accurate, and precise reversed phase liquid chromatography method was developed and validated for the quantitative estimation of flavonoid quercetin from the extract of Eruca Sativa. Method: The flavonoid was analyzed on RP-HPLC using Lichrosphere-100, C 18, column (25cm 4.6mm ID, 5μm) with UV detector system. The mobile phase consisting Methanol and water having -cyclodextrin (5mM) with 0.1 % orthophosphoric acid(70: 30 v/v) solution was used with flow rate of 1.0 mL min -1 and detection was performed at 370 nm wavelength. Results: The data showed that the linear ranges of Quercetin were 02-14 μg mL -1 (r=0.997), intraday and intermediate precision at three concentration level as % RSD (0.4550,0.7251, 0.5075; 0.4859,0.7999,0.5618), accuracy at three concentration level as % recovery (102.3 ± 0.8074,101.17± 0.9074,101.46 ± 0.1856 ), limit of detection; LOD (3.64042E-05 g mL -1 ) and limit of quantitation, LOQ (0.00011μg mL -1 ) and robustness ( in significant variations expressed as % RSD 0.13). Conclusion: The method was applied to quantitative analysis of Quercetin in plant extract of Eruca Sativa and was found to be simple, rapid and efficient.