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      Optimization of the Preparation Process for an Oral Phytantriol-Based Amphotericin B Cubosomes

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          Abstract

          In order to develop an oral formation of Amphotericin B (AmB) using phytantriol- (PYT-) based cubosomes with desirable properties, homogenization conditions were firstly investigated to determine their effects on the morphological and dimensional characteristics of cubosomes. Under the optimized homogenization conditions of 1200 bar for 9 cycles, cubosomes with reproducible, narrow particle size distribution and a mean particle size of 256.9 nm ± 4.9 nm were obtained. The structure of the dispersed cubosomes was revealed by SAXS (small-angle X-ray scattering) and Cryo-TEM (cryogenic transmission electron microscopy) as a bicontinuous cubic liquid crystalline phase with Pn3m geometry. To overcome the poor drug solubility and increase the drug-loading rate, a solubilization method was firstly used to develop cubosomes containing AmB. The encapsulation efficiency determined by HPLC assay was 87.8 % ± 3.4 % , and UV spectroscopy and stability studies in simulated gastric fluids further confirmed that AmB was successfully encapsulated in cubosomes.

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          Estradiol loaded PLGA nanoparticles for oral administration: effect of polymer molecular weight and copolymer composition on release behavior in vitro and in vivo.

          G Mittal, D Sahana, V Bhardwaj … (2007)
          The present investigation was aimed at optimization of estradiol loaded PLGA nanoparticulate formulations resulting in improved oral bioavailability and sustained release of estradiol by varying the molecular weight and copolymer composition of PLGA. Nanoparticles were prepared following emulsion-diffusion-evaporation method employing didodecyldimethyl ammonium bromide (DMAB) as stabilizer. The effect of polymer molecular weight and copolymer composition on particle properties and release behavior (in vitro and in vivo) has been reported. Drug release in vitro decreased with increase in molecular weight and lactide content of PLGA. Zero order release was obtained with low molecular weight (14,500 and 45,000 Da) PLGA, while high molecular weight (85,000 and 213,000 Da) and different copolymer compositions followed square root of time (Higuchi's pattern) dependent release. The bioavailability of estradiol from nanoparticles was assessed in male Sprague Dawley (SD) rats at a dose of 1 mg estradiol/rat. The in vivo performance of the nanoparticles was found to be dependent on the particle size, polymer molecular weight and copolymer composition. The C(max) of drug in the plasma was dependent on the polymer molecular weight and composition while particle size was found to influence the duration of release, suggesting smaller is better. The histopathological examination revealed absence of any inflammatory response with the formulations prepared of low/high molecular weight or high lactide content polymers for the studied period. Together, these results indicate that nanoparticulate formulations are ideal carriers for oral administration of estradiol having great potential to address the dose related issues of estradiol.
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            Amphotericin B: time for a new "gold standard".

            Luis Ostrosky-Zeichner, Kieren A. Marr, John H Rex … (2003)
            When introduced in 1959, amphotericin B deoxycholate (AmBD) was clearly a life-saving drug. Randomized studies demonstrating its efficacy were not thought to be necessary, and it was granted indications for many invasive fungal infections. Despite its formidable toxicities, AmBD is thus often used as the primary comparator in studies of invasive fungal infections. Safer lipid-based versions of amphotericin B (AmB) have been introduced, but difficulties with studying these agents generally led to licensure for salvage therapy, not primary therapy. However, the cumulative clinical experience to date with the lipid-based preparations is now adequate to demonstrate that these agents are no less active than AmBD, and, for some infections, it can now be stated that specific lipid-based preparations of AmB are superior to AmBD. Given their superior safety profiles, these preparations can now be considered suitable replacements for AmBD for primary therapy for many invasive fungal infections in clinical practice and research.
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              Lyotropic liquid crystalline phases formed from glycerate surfactants as sustained release drug delivery systems.

              S. H. Khoo, Christopher Davey, B Boyd … (2006)
              A new class of surfactants with glycerate headgroups, that form viscous lyotropic liquid crystalline phases in excess water, have been investigated for their potential to provide sustained release matrices for depot drug delivery. Oleyl glycerate and phytanyl glycerate were used as representative surfactants of this new class, and their behaviour compared with that of glyceryl monooleate (GMO). The surfactants were found to form reverse hexagonal phase (H(II)) in excess water, and the matrices were loaded with a series of model hydrophobic and hydrophilic drugs, (paclitaxel, irinotecan, glucose, histidine and octreotide), and the release kinetics determined. In all cases, the release behaviour obeyed Higuchi kinetics, with linear drug release versus square root of time. The H(II) phases released model drugs slower than the GMO cubic phase matrix. The oleyl glycerate matrix was found to consistently release drug faster than the phytanyl glycerate matrix, despite both matrices being based on H(II) phase. To further demonstrate the potential utility of these materials as drug depot delivery systems, an injectable precursor formulation for octreotide was also prepared and demonstrated to provide controlled release for the peptide. The stability of the H(II) phase to likely in vivo breakdown products was also assessed.
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                Author and article information

                Journal
                Title: Journal of Nanomaterials
                Abbreviated Title: Journal of Nanomaterials
                Publisher: Hindawi Limited
                ISSN (Print): 1687-4110
                ISSN (Electronic): 1687-4129
                Publication date Created: 2011
                Publication date (Print): 2011
                Volume: 2011
                Issue:
                Pages: 1-10
                Article
                DOI: 10.1155/2011/308016
                SO-VID: fffd8584-a1e4-494a-8cdc-e550c1c05063
                Copyright © © 2011
                License:

                http://creativecommons.org/licenses/by/3.0/

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