A RP-HPLC method for the simultaneous analysis of tocotrienol isoforms (TRF) and simvastatin (SIM) in SIM-TRF nanoparticles (NPs) was developed. Analytes were monitored by UV detection at 238 and 295 nm for SIM and TRF, respectively, using a gradient methanol/water elution. Calibration curves for TRF and SIM were linear over concentration range of 20-80 microg/mL and 1-10 microg/mL with correlation coefficients 0.9990 and 0.9991, respectively. The recovery of TRF and SIM from the NPs was in the range from 97.35 to 102.19% and from 92.71 to 104.35%, respectively. This developed method was successfully employed in quantifying both drugs in NPs for future use in cancer therapy.
[Show abstract][Hide abstract] ABSTRACT: A simple, rapid and selective method was developed for estimationof simvastatin from human plasma. The method involves simple protein precipitation techniques using etofylline as internal standard. Chromatographic separation was carried out on a reversed phase C<sub>18</sub> column using mixture of methanol: 2mM ammonium acetate and 500 μl of 0.5% formic acid (80:20, v/v) at a flow rate of 1.0 ml/min with UV-VIS detection at 418.35 nm. The retention time of simvastatin and internal standard were 5.41 and 1.086 min, respectively. The method was validated and found to be linear in the range of 1.0-10.0 ng/mL. An open, randomized, two-treatment, two period, single dose crossover, bioequivalence study in 12 fasting, healthy, male, volunteers was conducted. After dosing, serial blood samples were collected for the period of 24.0 h. Various pharmacokinetic parameters including AUC<sub>0–t</sub>, AUC<sub>0–∞</sub> , C<sub>max</sub>, T<sub>max</sub>, T<sub>½</sub>, and elimination rate constant (K<sub>el</sub>) were determined from plasma concentration of both formulations. Log transformed values were compared by analysis of variance (ANOVA) followed by classical 90% confidence interval for C , AUC<sub>0–t</sub> a nd AUC<sub>0–∞</sub> and was found to be within the range. These results indicated that the analytical method was linear, precise and accurate. Test and reference formulation were found to be bioequivalent.
Journal of Bioanalysis and Biomedicine 01/2009; DOI:10.4172/1948-593X.1000006
[Show abstract][Hide abstract] ABSTRACT: Vitamin E (VE) is a generic term that represents a family of compounds composed of various tocopherol and tocotrienol isoforms. Tocotrienols display potent anti-angiogenic and antiproliferative activities. Redox-silent tocotrienol analogues also display potent anticancer activity. The ultimate objective of this study was to develop semisynthetically C-6-modified redox-silent tocotrienol analogues with enhanced antiproliferative and anti-invasive activities as compared to their parent compound. Examples of these are carbamate and ether analogues of alpha-, gamma-, and delta-tocotrienols (1-3). Various aliphatic, olefinic, and aromatic substituents were used. Steric limitation, electrostatic, hydrogen bond donor (HBD) and hydrogen bond acceptor (HBA) properties were varied at this position and the biological activities of these derivatives were tested. Three-dimensional quantitative structure-activity relationship (3D QSAR) studies were performed using Comparative Molecular Field (CoMFA) and Comparative Molecular Similarity Indices Analyses (CoMSIA) to better understand the structural basis for biological activity and guide the future design of more potent VE analogues.
[Show abstract][Hide abstract] ABSTRACT: The primary objective of this study was to prepare nanostructured lipid carriers loaded with tocotrienol-rich-fraction of palm oil (TRF-NLCs) and to evaluate their antiproliferative effects against neoplastic +SA mammary epithelial cells. This necessitated optimizing the ultrasonic homogenization process parameters and the surfactant to lipid ratio within the NLCs. Therefore, sonication time and pulsar rate were initially evaluated for their effect on the size and polydispersity of the nanoparticles using a full factorial design. Also, varying the surfactant to lipid ratio from 0.25:1 to 3:1 was evaluated for its effect on the same responses. Optimal nanoparticles were obtained when dispersions containing a surfactant to lipid ratio of 0.5:1, with a total lipid concentration of 0.25 (w/v), were sonicated at 60% pulsar rate for 10 min. These parameters were subsequently used to prepare TRF-NLCs. TRF was loaded into the nanoparticles by substituting 10% (TRF-10-NLC) or 50% (TRF-50-NLC) of the lipid phase with TRF. In an extended stability study, no significant change in particle size of the TRF-NLCs was observed over 6 months of storage. In the cell culture studies, TRF-NLCs were shown to exhibit potent antiproliferative effect against neoplastic +SA mammary epithelial cells. The IC50 values of TRF-10-NLCs were 2-fold lower than the IC50 value of the reference TRF/BSA solution. In contrast, TRF-50-NLCs had comparable IC50 values as the TRF/BSA solution, which signified the importance of TRF encapsulation within NLCs on their activity. Furthermore, these findings suggested that TRF-NLCs may have potential value in the treatment of breast cancer.
Colloids and Surfaces A Physicochemical and Engineering Aspects 01/2010; 353(1-353):43-51. DOI:10.1016/j.colsurfa.2009.10.020 · 2.75 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.