Preparation and characterization of melittin-loaded poly (DL-lactic acid) or poly (DL-lactic-co-glycolic acid) microspheres made by the double emulsion method

Department of Pharmaceutics, School of Pharmaceutical Science, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang 110016, China.
Journal of Controlled Release (Impact Factor: 7.71). 11/2005; 107(2):310-9. DOI: 10.1016/j.jconrel.2005.07.001
Source: PubMed


The water soluble peptide, melittin, isolated from bee venom and composed of twenty-six amino acids, was encapsulated in poly (DL-lactic acid, PLA) and poly (DL-lactic-co-glycolic acid, PLGA) microspheres prepared by a multiple emulsion [(W1/O)W2] solvent evaporation method. The aim of this work was to develop a controlled release injection that would deliver the melittin over a period of about one month. The influence of various preparation parameters, such as the type of polymer, its concentration, stabilizer PVA concentration, volume of internal water phase and level of drug loading on the characteristics of the microspheres and drug release was investigated. It was found that the microspheres of about 5 microm in size can be produced in high encapsulation (up to 90%), and the melittin content in the microspheres was up to 10% (w/w). The drug release profiles in vitro exhibited a significant burst release, followed by a lag phase of little or no release and then a phase of constant melittin release. The type of polymer used was a critical factor in controlling the release of melittin from the microspheres. In this study, the rate of peptide release from the microspheres correlated well with the rate of polymer degradation. Moreover, melittin was released completely during the study period of 30 days, which agreed well with the polymer degradation rate.

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    • "One of the reasons for this phenomenon may be that the more of PVA molecules are absorbed on the surfaces between organic phase and aqueous phase, the lower is the interfacial tension between the oil and aqueous phase (Ito et al. 2007). Another reason may be the increase in viscosity of the outer aqueous phase with increasing concentration of PVA, which prevents the emulsion droplets from coalescence (Cui et al. 2005). Both of these resulted in smaller and more stable emulsion droplets. "
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    ABSTRACT: Lappaconitine instead of its hydrobromide salts has been encapsulated in poly (lactide-co-glycolide) acid (PLGA) microspheres by the simple o/w emulsion solvent evaporation technique. The effects of several variables including emulsifier (polyvinyl alcohol, PVA) concentration, stirring speed, PLGA concentration and drug/polymer mass ratios on quality of microspheres have been investigated. The particle size and size distribution can be controlled by PVA concentration, stirring speed and PLGA concentration. The entrapment efficiency and the burst release of lappaconitine from drug-loaded microspheres were dominantly affected by the drug/polymer mass ratio and PVA concentration. The best parameters of formulation were 1.5% PVA, the PLGA concentration of 50 g/L, and the stirring speed of 800 rpm and drug/polymer of 1:5. The optimized formulation has a mean particle size of 19.3 +/- 0.93 microm, mean entrapment efficiency of 70.77 +/- 3.23% and mean drug loading of 11.45 +/- 0.47%. Based on the optimized parameters of formulation, the effects of oil/aqueous solubility partition ratio of drug on entrapment efficiency of drug-loaded microspheres prepared by o/w emulsion solvent evaporation were further studied. A good linear relation existed between the partition ratio and entrapment efficiency. The optimized microspheres were characterized by SEM, FT-IR, DSC and XRD. SEM shows spherical and smooth surface and uniform size distribution. The results of DSC, FT-IR study reveal no interaction between drug and polymer. The results of the XRD study indicate lappaconitine trapped in microsphere exists in form of an amorphous or disordered crystalline status in polymer matrix. The in vitro release models were evaluated with two different groups of drug-loaded microspheres including microspheres washed with distilled water and 0.01N HCL, respectively. The drug release profile of lappaconitine-loaded microspheres washed with distilled water agreed with zero order equation and that of the latter better agreed with first order equation.
    Pharmazie 09/2011; 66(9):654-61. DOI:10.1691/ph.2011.1042 · 1.05 Impact Factor
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    • "Such biodegradable and biocompatible polymers include polylactic acid (PLA), polyglycolic acid (PGA), and polylactic-co-glycolic acid (PLGA). The latter is approved for therapeutic use by the Food and Drug Administration (FDA) and is one of the most widely used polymers in nano- and microparticle production [31, 67]. "
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    08/2011; 2011(20):936438. DOI:10.1155/2011/936438
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    • "This could be due to electric interactions between negatively charged Carboxyl ions in PLGA and positively charged ammonium ions in triptoreline, resulting in the formation of a barrier which efficiently prevents triptoreline leaving or diffusing from the microspheres during the preparation process. This trend was similar to the results obtained by Cui et al, for the encapsulation of melittin (21). "
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    ABSTRACT: Triptoreline is a potent agonist of luteinizing hormone-releasing hormone, currently used in the treatment of prostatic cancer where therapy may be required over months or years. Frequent injection of drug decreases patients' compliance. The present study describes the formulation of a sustained release microparticulate drug delivery system containing triptoreline acetate, using poly (D,L lactide-co-glycolide) (PLGA). Biodegradable microspheres were prepared using 50: 50 PLGA by a water in-oil-in-water (w/o/w) double emulsion-solvent evaporation procedure and characterized for drug content and drug release rate using the a HPLC method, particle size distribution using the laser diffraction method, and surface morphology using scanning electron microscopy and drug release rate. Effect of critical process parameters and formulation variables; i.e. volume of inner water phase, addition of NaCl to the outer aqueous phase (W2), addition of different types and amounts of emulsifying agents on microsphere characteristics; were investigated. Microspheres prepared were spherical with a smooth surface, but addition of poloxamer to the first emulsion produced microspheres with large pores. Size of microparticles was dependent on the type, as well as the amount of co-encapsulated surfactants. Increasing the inner water phase volume resulted in larger particles with a lower encapsulation efficiency. Low concentrations of Span 20 decreased triptoreline release rate, whereas the addition of poloxamer or high concentrations of Span 20 increased the drug release rateit. In conclusion, by selecting an appropriate level of the investigated parameters, spherical microparticles with encapsulation efficiencies higher than 90% and a prolonged triptoreline release over 45 days were obtained. © 2010 by School of Pharmacy.
    Iranian journal of pharmaceutical research (IJPR) 02/2010; 9(4-4):369-378. · 1.07 Impact Factor
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