| With low water solubility and high membrane permeability, protein and peptidedrugs are short at in-vivo half-life, while poor in stability. Polymeric drug deliverysystems can improve the bioactivity of protein and peptide drugs in the body. Amongpolymeric drug delivery systems, biodegradable polymer is considered as perfectmaterial for its safety, non-toxicity, and inexistence of side effect. Polylactic-glycolicacid (PLGA) is the most widely studied pharmaceutical carrier because of its highbiocompatibility and bio-degradability, and as a novel drug delivery system is one ofthe hot spots in recent years. Currently, PLGA nanoparticles are mainly prepared bysolvent evaporation method, solvent diffusion method or double emulsion solventevaporation method. But all the above methods do not apply to water-soluble andpharmaceutical sensitive protein drugs.In this paper, to address the above issue, emulsion solvent diffusion and doubleemulsion solvent evaporation technique were combined as a novel W/O/W emulsionsolvent diffusion technique.. In addition, PLGA was used as a carrier, and partiallywater-soluble glycerol triacetate as organic solvent. We mainly focused on optimizingthe preparation technology, including the selection and concentration of the emulsifier,the concentration of polymer, the aqueous phase to oil phase volume ratio, externalaqueous phase to colostrum volume ratio, diffusion phase component andphacoemulsification time. The results showed that: F-68as a emulsifier is more suitedfor double emulsion solvent diffusion technique than the others in this study; Theinner diameter of the nanoparticles decreased with the increase of F-68concentrationin inner water, increased linearly with the increase of polymer concentration and theincrease of the outer aqueous phase volume ratio; Inner aqueous phase to oil phasevolume ratio principally effects the morphology of nanoparticles; Increasing ethanolcontent of the dispersed phase resulted in the increasing of expanded phase and the solubility of organic solvent, accelerating the curing of droplets. Neither too short nortoo long of phacoemulsification time is conducive to the preparation of nanoparticles.Through single factor analysis and optimization of preparation technique we got bestpreparation conditions, and ultimately obtained particle size less than200nm,morphologically smooth and well-dispersed nanoparticles.DhHP-6is an artificially synthesized peptide analogue, which is confirmed as acure for a variety of diseases by its obliterating of radicals, and is with good prospectsfor development. However, DhHP-6is short in half-life and easily inactivated in vivo,just like the other protein and peptide. In this paper, DCC/NHS method was used tosuccessfully achieve chemical coupling of DhHP-6and PLGA to obtain apharmaceutically active material, PLGA-DhHP-6, the activity of which was wellmaintained. By optimized double emulsion solvent diffusion technique we preparedPLGA-DhHP-6nanoparticles to be compared with DhHP-6-in-PLGA nanoparticlesunder the same preparation conditions. We found that the drug loading of the formerwas nearly twice of the latter, indicating that covalent coupling of drug with thepolymer matrix material is an effective way to improve drug loading. However, allthese two nanoparticles showed initial burst of release in vitro release experiments.Although PLGA-DhHP-6nanoparticles’ accumulated releasing percent was higherthan PLGA nanoparticles, the drug in it remained low activity after release comparedwith PLGA nanoparticles. In this paper, ensuring the activity of DhHP-6as apreceding condition, we successfully covalent coupled PLGA and DhHP-6and byW/O/W double emulsion solvent diffusion technique, we successfully improve drugloading of DhHP-6, one of the water-soluble protein drugs. Furthermore, the releasingpercent of drug in DhHP-6is also increased by a certain degree. |
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