Current Issue : July - September Volume : 2011 Issue Number : 3 Articles : 8 Articles
Background\r\nIn Central and South America and Eastern and Southern Africa, Plasmodium vivax infections accounts for 71-81% and 5% of malaria cases, respectively. In these areas, chloroquine (CQ) remains the treatment of choice for P. vivax malaria. In addition, CQ has recently proven to be an effective HIV-1 therapeutic agent. There is a dire need to continue monitoring quality of CQ as there is a major influx of substandard and fake formulations into malaria-endemic countries. The use of fake/substandard drugs will result in sub-therapeutic levels endangering the patient and possibly select for parasite resistance. The aim of this study was to develop an inexpensive, simple antibody-based ELISA to measure CQ concentrations in tablets and in plasma.\r\nMethods\r\nA monoclonal antibody (MAb) that reacts with the N-side chain of the CQ molecule was prepared by use of a CQ analogue. A specific and reliable ELISA for detection of CQ was developed. The developed assay was validated by measuring CQ in tablets sold in Denmark, India and Sudan. Furthermore, kinetics of CQ concentrations in plasma of four volunteers, who ingested two tablets of Malarex�® containing, 250 mg CQ base, were measured before drug intake, three hours later and thereafter at days 1, 3, 7, 14, 21 and 28. The same plasma samples were simultaneously measured by high performance liquid chromatography (HPLC).\r\nResults\r\nThe ELISA proved an easy-to-handle and very sensitive tool for the detection of CQ with a lower limit of detection at 3.9 ng/ml. ELISA levels of CQ in plasma showed high agreement with the levels obtained by HPLC (r = 0.98). The specificity in the negative control group was 100%.\r\nConclusion\r\nThe developed ELISA can be used for quality screening of CQ in pharmaceutical formulations and for drug monitoring in malaria and in other infectious diseases, such as HIV, where CQ proved to be an effective therapeutic agent. The methodology has been exploited to develop monoclonal antibodies for the drugs used in artemisinin-based combination therapy (ACT)....
The objective of the present study is to formulate and characterize a nanoparticulate-based formulation of a macromolecule in a hydrophobic ion pairing (HIP) complex form. So far, HIP complexation approach has been studied only for proteins with molecular weight of 10ââ?¬â??20?kDa. Hence, we have selected bovine serum albumin (BSA) having higher molecular weight (66.3?kDa) as a model protein and dextran sulphate (DS) as a complexing polymer to generate HIP complex. We have prepared and optimized the HIP complex formation process of BSA with DS. Ionic interactions between basic amino acids of BSA with sulphate groups of DS were confirmed by FTIR analysis. Further, nanoparticles were prepared and characterized with respect to size and surface morphology. We observed significant entrapment of BSA in nanoparticles prepared with minimal amounts of PLGA polymer. Finally, results of circular dichroism and intrinsic fluorescence assay have clearly indicated that HIP complexation and method of nanoparticle preparation did not alter the secondary and tertiary structures of BSA....
The interest using novel drug delivery systems to improve oral bioavailability of drug with poor solubility is increasing. In this study, a new oral delivery system, polybutylcyanoacrylate nanoparticles (PBCNs), was introduced to improve the oral bioavailability of puerarin (PUE). PUE-loaded PBCN was successfully prepared by anionic polymerization method. Characterization of PUE-loaded PBCN was evaluated with morphology, size, zeta potential, and in vitro release study. The PBCN loading PUE exhibited a spherical shape under transmission electron microscopy with an average size of 159.4?nm, and the zeta potential was -15.0?mV. The in vitro release of PUE-loaded PBCN showed an initial burst release followed by a sustained release. Physicochemical state of PUE in PBCN was investigated by differential scanning colorimetry, X-ray diffraction, and Fourier transform infrared spectroscopy. The results indicated that PUE in PBCN was in a noncrystalline state. The oral pharmacokinetic study in rats showed that the relative bioavailability of PUE-encapsulated PBCN to the crude PUE was more than 550%. It can be concluded that PBCN as an oral drug carrier can significantly improve the oral bioavailability of PUE....
The successful implementation of human embryonic stem cells (hESCs)-based technologies requires the production of relevant numbers of well-characterized cells and their efficient long-term storage. In this study, cells were microencapsulated in alginate to develop an integrated bioprocess for expansion and cryopreservation of pluripotent hESCs. Different three-dimensional (3D) culture strategies were evaluated and compared, specifically, microencapsulation of hESCs as: i) single cells, ii) aggregates and iii) immobilized on microcarriers. In order to establish a scalable bioprocess, hESC-microcapsules were cultured in stirred tank bioreactors.\nThe combination of microencapsulation and microcarrier technology resulted in a highly efficient protocol for the production and storage of pluripotent hESCs. This strategy ensured high expansion ratios (an approximately twenty-fold increase in cell concentration) and high cell recovery yields (>70%) after cryopreservation. When compared with non-encapsulated cells, cell survival post-thawing demonstrated a three-fold improvement without compromising hESC characteristics.Microencapsulation also improved the culture of hESC aggregates by protecting cells from hydrodynamic shear stress, controlling aggregate size and maintaining cell pluripotency for two weeks.This work establishes that microencapsulation technology may prove a powerful tool for integrating the expansion and cryopreservation of pluripotent hESCs. The 3D culture strategy developed herein represents a significant breakthrough towards the implementation of hESCs in clinical and industrial applications....
Freeze-drying a biodegradable polymer, poly(L-lactic acid) (PLLA), from 1,4-dioxane solutions provided very porous spherical particles of ca. 3?mm in radius with specific surface area of 8ââ?¬â??13?m2 g-1. The surface of the particle was found to be less porous compared with its interior. To apply the freeze-dried PLLA (FDPLLA) to drug delivery system, its morphology and drug releasing kinetics were investigated, bovine serum albumin (BSA) being used as a model drug compound. Immersion of FDPLLA into a BSA aqueous solution gave BSA-loaded FDPLLA, where mass fraction of the adsorbed BSA reached up to 79%. Time-dependent release profile of BSA in water suggested a two-step mechanism: (1) very rapid release of BSA deposited on and near the particle surface, which results in an initial burst, and (2) leaching of BSA from the interior of the particle by the diffusion process. It was suggested that the latter process is largely governed by the surface porosity. The porosity of both the interior and surface was found to decrease remarkably as the concentration of the original PLLA/1,4-dioxane solution increases, C0. Thus, C0 is a key parameter that controls the loading and releasing of BSA....
A congealable disperse phase encapsulation method was used to prepare controlled release wax microspheres of lamivudine to increase the efficacy of anti retroviral drug, lamivudine against HIV infections and decrease its gastric unwanted effects. The prepared lamivudine loaded wax microspheres were evaluated for drug content, particle size distribution, surface morphology, in-vitro release studies, dissolution efficiency (DE5%) and release kinetic study. Drug release from wax was compared with the release behavior of commercially available formulation Lamidine®150. The Carnauba wax microspheres were spherical in shape and non aggregated. The drug content was found to be 40.54-62.93 %W/W. The particle size was ranged from 13-17 µm in size and in-vitro release profile showed that the prepared wax microspheres effectively controlled the release of lamivudine compared to the market product. (DE5%) was ranged from 48.185-62.96%. The in vitro release data were in favor of diffusion release kinetics (for formulae F5, F6 and F7) and koresmeyer-peppas release kinetics (for F8). The values of n were ≤ 0.43 indicating Fickian (case I) diffusion transport for all formulae (except for formulae F8). Marked retardation of lamivudine release may provide a useful controlled release of anti retroviral drug therapy....
Solid dispersions were prepared by a conventional solvent evaporation method from the water-insoluble model drug 10-hydroxycamptothecin (HCPT) and monomethoxypoly(ethylene glycol) 2000 (mPEG 2000). And then one type of novel biodegradable nanoparticles, the solid dispersion (HCPT/mPEG-CHO) grafted with carboxymethylchitosan (HCPT/mPEG-g-CMCTS) was synthesized. The increase in HCPT solubility of solid dispersion was up to 21-fold compared with the original drug. With the increasing of the amount of mPEG-CHO, solubility of HCPT was from 7.71?�µg/mL to 25.82?�µg/mL. Colloid systems based on solid dispersion were stable in aqueous medium at 5�°C. After 5 months storage at 25�°C, the solid dispersions do not change at all. HCPT/mPEG-g-CMCTS was synthesized by grafting reaction of carboxymethylchitosan with mPEG-CHO to form Schiff base which is sensitive to acid environment. The release rate of HCPT from this conjugate in pH 5.4 was much higher than that in the environment of pH 7.4 and p H 4.5. The cumulative release percentages are 45%, 25%, and 15%, respectively. The cumulative release percentage of HCPT in conjugate was only 15% within 85?h while the original drug was up to 70% in pH 7.4, showing a significant slow-release property. This drug model can be attractive candidates as delivery biosystems in tumor therapy....
Non-virally inactivated cryoprecipitate prepared by blood banks is still used in the developing world, for the treatment of bleeding disorders such as factor VIII (FVIII) deficiency which induces haemophilia type A. As a consequence, patients receiving cryoprecipitate are at high risk of being infected by plasma-borne viruses, such as hepatitis B (HBV) or C viruses (HCV). Moreover, the high concentration of contaminating proteins in the cryoprecipitate evoked the need for development of a method for production of safe purified freeze-dried FVIII concentrate with increasing stability. In this work, FVIII was fractionated using modified techniques including aluminum hydroxide hydrogel (Al(OH)3) with polyethylene glycol (PEG) 4000 or glycine as precipitating agents with viral inactivation using betapropiolactone (BPL). The highest yield was exposed to accelerated stability using two different polysaccharides trehalose and sucrose. BPL as an inactivant has proved to inactivate Vesicular Stomatitis Virus (VSV) as HCV model, within 60-90 min post treatment at 37 oC and 4 oC in FVIII concentrate respectively. However, it was found to be degradative to FVIII although not affecting the total protein profile. Thus; it can be used for cold sterilization of other factors than FVIII. In this work, lyophilized FVIII concentrate supplemented with 60 mM sucrose or 60 / 90 mM trehalose as stabilizers were subjected for further accelerated stability studies , including forced degradation at 37 ºC for 10 days. Initial Activated Partial Thromboplastin Time (APTT) and percentage activity of the coagulation FVIII were found to be the highest in case of sucrose stabilization indicating a higher stabilizing effect of sucrose than trehalose on FVIII concentrate....
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