Preparation of biodegradable porous poly(butylene succinate) microspheres

Abstract

The aim of this study was to determine the optimal conditions for the fabrication of porous microspheres based on poly(butylene succinate), PBS. The biodegradable non-porous PBS microspheres were prepared by the oil-in-water (o/w) emulsion solvent evaporation method using poly(vinyl alcohol), PVA, as the surfactant. Fabrication conditions, such as stirring rate, organic/aqueous ratio, PBS concentration and surfactant (PVA) concentration, which have an important influence on both the particle size and the morphology of the microspheres, were varied. Scanning electron microscopy, SEM, observations confirmed the size, size distribution and surface morphology of the microspheres. The optimal conditions for the preparation of the non-porous microspheres were found to be: concentration the PBS solution, 10 mass%; PVA concentration, 1 mass%; the organic/ aqueous ratio CHCl3/H2O = 1/20 and stirring rate 800 rpm. Porous PBS microspheres were fabricated under the optimal conditions using various amounts of hexane and poly(ethylene oxide), PEO, as porogens. The influence of the amount of porogen on the pore size and the particle size was investigated using SEM and the apparent density. The microspheres exhibited various porosities and the pore sizes. The average particle size of the microspheres with PEO as the porogen was from 100 to 122μm and that of the microspheres with hexane as the porogen was from 87 to 97μm. The apparent density of the porous microspheres with PEO as the porogen, from 0.16 to 0.23 g/cm3, was much smaller than the non-porous microspheres, 0.40 g/cm3. In the in vitro degradation experiments, the porous microspheres were incubated in phosphate buffer solution (pH 7) at 37°C. After incubating for one month, the microspheres showed significant extent of the hydrolytic degradation of the porous PBS microspheres.

Cilj ovog rada je bio pronalaženje optimalnih uslova za dobijanje poroznih mikrosfera na bazi biodegradabilnog poli(butilensukcinata), PBS. Neporozne PBS mikrosfere su dobijene emulzionim postupkom uz otparavanje rastvarača u prisustvu poli(vinil alkohola), PVA, kao stabilizatora emulzije. Tokom izrade mikrosfera menjani su uslovi kao što su: brzina mešanja, odnos organska/vodena faza, PBS koncentracija i koncentracija emulgatora (PVA), koji imaju značajan uticaj na veličinu čestica i morfologiju mikrosfera. Skenirajućim elektronskim mikroskopom (SEM) utvrđena je veličina mikrosfera, raspodela veličina čestica kao i morfologija površine mikrosfera. Ustanovljeni su optimalni uslovi za dobijanje neporoznih mikrosfera: koncentracija PBS rastvora od 10 mas%, PVA koncentracija od 1 mas%, odnos organska/vodena faza = 1/20 i brzina mešanja 800 min-1. Porozne PBS mikročestice su pravljene pri optimalnim uslovima u prisustvu različitog sadržaja heksana i poli(etilenoksida), PEO, kao porogena. Kao rezultat dobijeno je da mikrosfere pokazuju različitu poroznost kao i različitu veličinu pora unutar čestica. Srednja veličina čestica mikrosfera kod kojih je korišćen PEO kao porogen bila je od 100 do 122 μm, a kod mikrosfera sa heksanom kao porogenom srednja veličina čestica se kretala od 87 do 97 μm. Prividna gustina poroznih čestica kod mikrosfera sa PEO kao porogenom bila je u opsegu od 0,16 do 0,23 g/cm3, dosta manje od prividne gustine neporoznih mikorsfera, 0,40 g/cm3. In vitro degradacioni testovi poroznih mikrosfera su izvođeni u puferskom rastvoru (pH 7) na 37°C. Posle inkubacije mikrosfera od jednog meseca u puferu ustanovljeno je da dolazi do delimične degradacije polimernih mikrosfera.