Poly DL-lactic Acid Research Articles

Phase-sensitive polymer-based controlled delivery systems of leuprolide acetate: In vitro release, biocompatibility, and in vivo absorption in rabbits

Leuprolide acetate (LA) is a synthetic analog of gonadotropin releasing hormone. It is effective in prostrate cancer treatment only when its desired concentration in blood is maintained for longer duration. Therefore, the purpose of this study was to investigate the in vitro release, biocompatibility, and in vivo absorption of LA from phase-sensitive polymer delivery systems capable of delivering it at a controlled rate for longer duration. Phase-sensitive formulations were prepared by dissolving dl-polylactic acid ( dl-PLA) in a mixture of organic solvents, benzyl benzoate (BB) and benzyl alcohol (BA). LA was incorporated into the polymer solution by homogenization. In vitro release was studied into 15 ml of releasing media contained in a vial which was maintained at 37 °C in a reciprocal shaking water bath. The amount of LA in the released samples was analyzed by stability indicating HPLC method. The biocompatibility of polymer formulations was investigated by in vitro 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. In vivo absorption of LA from delivery systems was studied in rabbits. Blood samples were analyzed for LA and testosterone contents by commercially available immunoassay kits. In vitro release studies showed a greater release of LA from formulations containing a greater proportion of BA (hydrophilic fraction) in the solvent mixture. In vitro biocompatibility study showed significantly ( p < 0.05) higher cell viability in growth media diluted with polymer extract than the control. In vivo absorption of LA and its effect on testosterone level in rabbits from the delivery system showed a sustained plasma level of LA up to 12 weeks which suppressed the testosterone plasma concentration to castration level beginning from 14th day until 90 days. Thus, phase-sensitive polymer delivery systems of LA were biocompatible and delivered LA at a controlled rate both in vitro and in vivo to keep testosterone plasma concentration at a castration level up to 3 months.

The effects of types of degradable polymers on porcine chondrocyte adhesion, proliferation and gene expression

Understanding how a specific biomaterial may influence chondrocyte adhesion, proliferation and gene expression is important in cartilage tissue engineering. In this study several biodegradable polymers that are commonly used in tissue engineering were evaluated with respect to their influence on chondrocyte attachment, proliferation and gene expression. Primary cultures of porcine chondrocytes were performed in films made of poly-L-lactic acid (PLLA), poly-D,L-lactic acid (PDLLA), poly-(lactide-co-glycolide) (PLGA), or polycaprolactone (PCL). Chondrocytes adhered to PDLLA or PLGA after 1-day incubation better than to PLLA or PCL. After 7 or 14 day culture, the cell numbers on PDLLA or PLGA was still higher than PLLA or PCL. The results suggested that cell attachment and growth might depend on degradation rate of biodegradable polymers. Along with the fact that PDLLA or PLGA supported expression of chondrocyte specific genes more than PLLA or PCL, the former two materials seemed to be more suitable for cartilage tissue engineering than the latter ones. Besides, we found that chondrocyte phenotype prior to seeding was important in the expression of ECM proteins.

Biodegradable implantable fluconazole delivery rods designed for the treatment of fungal osteomyelitis: Influence of gamma sterilization

Fluconazole poly(D,L-lactic) acid (PLA) and poly(L-lactic) acid (L-PLA) implantable delivery rods were studied, in vitro and in vivo, as an alternative treatment of fungal osteomyelitis. Implantable rods loaded with 5% fluconazole (FLU) were prepared by the injection-molding method and sterilized by gamma-irradiation at a dose of 25 kGy. Loading efficiency, physical chemistry (high performance liquid chromatography, X-ray diffraction, gel permeation chromatography), and in vitro and in vivo release assays were performed to evaluate the novel delivery systems and the sterilization effect on implant characteristics. In spite of polymer degradation after gamma-irradiation, the loading efficiency, chemical stability, and crystallographic structure of FLU were not affected. In vivo studies were carried out in femoral bone marrow of rabbits. Approximately 85 and 80% of the total dose were released within 12 and 4 weeks from PLA and L-PLA rods, respectively. This showed a faster release rate of FLU in vivo than in vitro, showing almost zero-order kinetics from PLA rods.

Use of Absorbable Poly (D,L) Lactic Acid Plates in Cranial-Vault Remodeling: Presentation of the First Case and Lessons Learned about Its Use

To present the first clinical use of a new bioabsorbable material, poly (D,L) lactic acid (PDLLA), in pediatric cranial-vault remodeling procedures. This discussion will highlight the benefits and detriments of PDLLA in comparison with currently used absorbable plating systems. This was a case study documenting the first North American case in which PDLLA was used to treat craniosynostosis. Evaluation of pure PDLLA, a copolymer product of the mixture of poly L-lactic acid and its D-isomer, was used in an 8-month-old boy with a severe phenotypic expression of sagittal craniosynostosis. No signs of elevated intracranial pressure were present, and the neurological examination did not show impairments. Total cranial-vault remodeling with the "hung-span" technique was performed. The Resorb X system, containing 2.2-mm screws and 0.6- to 1-mm-thick plates, was used to stabilize the reconstructed cranial vault. No surgical complications occurred. The preoperative cranial index measured 62. The scaphocephalic appearance of the skull was eliminated, and the cranial index was normalized to 77. The screws and plates were less palpable than other plating systems. Twelve months postoperatively, none of the plates and screws were identifiable by external palpation. Resorb X has been successfully used in the treatment of sagittal craniosynostosis. Its rapid rate of resorption and lower profile make it an advantageous system for pediatric skull reconstruction. This represents the first use of this product in the United States for any pathology.

Formulation and Characterization of Poly-D, L-Lactic Acid Nanoparticles Containing Daunorubicin

The regular spherical poly-D, L-lactic acid (PDLLA) nanoparticles containing DNR are produced using a double-emulsion solvent evaporation process. The products morphology is characterized by a laser light-scattering particle size analyzer and scanning electron microscopy. Results show a mean diameter in 546.9 nm with narrow size distribution and homogeneous particle production. The encapsulation efficiency is evaluated by UV spectra. The results indicate that drug contents and loading efficiency are 14.34% and 72.9% respectively, and the drug release profile shows a biphasic phenomenon.

Three‐Dimensional Bioactive and Biodegradable Scaffolds Fabricated by Surface‐Selective Laser Sintering

A new method of surface-selective laser sintering (SSLS) leads to the fabrication of three-dimensional (3D) composite scaffolds (spatial resolution ∼200 μm) that are both bioactive and biodegradable. Moreover, the scaffolds can have very precise dimensions and intricate structure. Conventionally, in selective laser sintering (SLS), the polymer absorbs infrared (λ=10.6 μm) radiation and this leads to a volumetric absorption by the whole polymer particle. In other words, each particle of polymer is completely melted and fuses to the next in order to form the desired morphology. In our experiments we have used near-infrared (λ=0.97 μm) laser radiation, which polymer particles do not absorb at all. To initiate the sintering process a small quantity (< 0.1 wt.-%) of carbon microparticles were homogeneously distributed on the surfaces of the polymer particles. Thus, the melting process was limited to only the surfaces of each particle. The carbon microparticles are strong absorbers of laser radiation, and this opens up the technique to a range of polymers that up till now could not be processed by laser sintering. More importantly, since the laser melts only the surfaces of the particles, delicate bioactive species trapped within each particle retain their activity throughout the processing. We have demonstrated the application of this technique by the incorporation of the enzyme ribonuclease A into particles of poly(d,l-lactic) acid (PLA) and the assembly of 3D matrices at three different laser intensities, using a 0.97 μm wavelength continuous wave (CW) diode laser.

Biodegradable Self-Expanding Poly-L/D-Lactic Acid Vascular Stent:A Pilot Study in Canine and Porcine Iliac Arteries

To report results of an in vivo pilot study to evaluate the biocompatibility and delivery system of a new biodegradable vascular stent and validate the study design. Two self-expanding intravascular stents, a biodegradable poly-D/L-lactic acid (PLA) and a medical stainless steel stent (Wallstent) were implanted in the common iliac arteries of 2 postpuberal female pigs and 3 laboratory-bred beagle dogs. Specimens were harvested after 45 days in the dogs and 32 days in the pigs for histomorphometry of the stented iliac artery segments. Preliminary measurements were made to assess the reliability of the quantitative histomorphometric measurements before final measurements. Histomorphometry analyses showed that mean luminal diameter and area were decreased in the PLA stent group (1.97+/-0.48 mm and 14+/-6.4 mm2, respectively) compared to the control stent group (4.28+/-0.83 mm and 61+/-19 mm2, respectively). The intimal thickness was higher in the PLA stent group (0.65+/-0.07 mm) than in the control group (0.44+/-0.21 mm). The mean injury score was 0.19+/-0.12 in the PLA stent group and 0.78+/-0.39 in the controls. In the PLA stent group, the mean inflammation score was 1.46+/-0.78 compared to 0.58+/-0.40 in the control group. There were no differences observed between the animal models. The PLA stent showed increased neointimal formation and reduced patency during early follow-up. Mechanical properties of the new biodegradable vascular stents are still inadequate, and the stent and the delivery device require modifications. The study methods were assessed as reliable and reproducible.

Development of implant tablet for a week-long sustained release

An implant tablet for a week-long sustained release was developed by the direct compression method using poly- dl-lactic acid (PLA) and poly( dl-lactic acid-co-glycolic acid) copolymer (PLGA) as a matrix and phenol red (PR) as a model drug. The in vitro release was affected by formulations, especially by drug content and polymer species. The release rate correlated with the rate of absorption of water. The implant tablet (30 mg) containing 1 mg of PR, prepared using PLGA (MW 10,000; lactic acid/glycolic acid=1:1, mol/mol) by compression at 50 kg/cm 2 for 10 s, was found to efficiently exhibit a week-long sustained release in vitro, and applied in vivo. The remaining amount or plasma concentration of PR after s.c. administration of the implant tablet to rats demonstrated that the implant tablet showed a week-long sustained release in vivo. The present implant tablet is suggested to be useful as a drug delivery system for supplying drugs for approximately 1 week.

Long-term assessment of a novel biodegradable paclitaxel-eluting coronary polylactide stent.

The aim of this study was to assess technical feasibility, biocompatibility, and impact on coronary stenosis of a new biodegradable paclitaxel-loaded polylactide stent. Due to high rates of in-stent restenosis and permanent nature of metal stent implants, synthetic polymers have been proposed as surrogate materials for stents and local delivery systems for drugs. Paclitaxel was shown to inhibit vascular smooth muscle cell proliferation and migration. A novel biodegradable double-helical stent was manufactured using controlled expansion of saturated polymers (CESP) for the moulding of a bioresorbable poly(D,L)-lactic acid (PDLLA). A modified balloon catheter for stent deployment was developed according to the mechanical stent properties. Twelve paclitaxel-loaded (170 microg) polylactide stents, 12 unloaded polylactide stents, and 12 316L bare metal stents were deployed in porcine coronary arteries of 36 animals. Six pigs of each group were sacrificed after 3 weeks and 3 months, respectively, for every setting. Drug release kinetics as well as histomorphometrical and histopathological analyses were performed. A slow paclitaxel release kinetic for more than 2 months and therapeutic tissue concentrations were demonstrated. Coronary stenosis after implantation of paclitaxel-loaded stents (30+/-5% or 49+/-4%) was significantly inhibited compared to unloaded PDLLA stents (65+/-10%, P=0.021 or 71+/-4%, P=0.004) and metal stents (53+/-6% or 68+/-8%, P=0.029 and P=0.020) after 3 weeks or 3 months. Early complete endothelialisation was shown. Nevertheless, a local inflammatory response to the polylactide as a result of the polymer resorption process was observed. This novel polylactide stent showed sufficient mechanic stability, and by incorporation of paclitaxel, a significant potential to reduce restenosis development after vascular intervention was seen.

A device for long term, in vitro loading of three-dimensional natural and engineered tissues.

In vitro studies of mechanical loads applied to three-dimensional tissue constructs are important to the design and production of functional, engineered bone tissue. This study reports the development and characterization of a mechanical device capable of subjecting a three-dimensional section of natural or engineered tissue to precise, reproducible four-point bending deformations over a range of programmable magnitudes and frequencies. To test the biological and mechanical capabilities of the system, a low-cycle (360 cycles/day), medium-range strain (2500 microstrain), long-term (16 day) loading regime was applied to rat bone marrow stromal cells cultured in porous DL-polylactic acid scaffolds. Cells proliferated in culture throughout the experiment, and with time showed an increase in alkaline phosphatase expression per cell. Calcium and phosphorus mineral deposition by the unloaded group was significantly greater (p<0.05) than that deposited by the loaded group. The molar ratio of calcium to phosphorus in the unloaded group (0.94:1) was significantly greater (p<0.05) than that of the loaded group (0.41:1). The loading device presented here is a tool which can be used to help elucidate contributions of mechanical loading/fatigue on biodegradable materials, as well as study the effects of mechanical loading on natural or engineered tissues in vitro.

Contact profilometry and correspondence analysis to correlate surface properties and cell adhesion in vitro of uncoated and coated Ti and Ti6Al4V disks

A fundamental goal in the field of implantology is the design of specific devices able to induce a controlled and rapid “osseointegration”. This result has been achieved by means of surface modifications aimed at optimizing implant-to-bone contact; furthermore, bone cell adhesion on implant surface has been directly improved by the application of biomolecules that stimulate new tissue formation, thus controlling interactions between biological environment and implanted materials. Actually, methods for biochemical factor delivery at the interface between implant surface and biological tissues are under investigation; a reliable technique is represented by the inclusion of biologically active molecules into biocompatible and biodegradable materials used for coating implant surface. This paper focuses the application of three polymeric materials already acknowledged in the clinical practice, i.e. poly- l-lactic acid (PLLA), poly- dl-lactic acid (PDLA), and sodium alginate hydrogel. They have been used to coat Ti (Ti2) and Ti6Al4V (Ti5) disks; their characteristics have been determined and their performances compared, with specific regard to the ability in allowing osteoblast adhesion in vitro. Moreover, profilometry data analysis permitted to identify a specific roughness parameter (peak density) which mainly controls the amount of osteoblast adhesion.

Preparation and characterization of biodegradable PLA polymeric blends

The purpose of this study was to fine-tune the mechanical properties of high molecular-weight poly- l-lactic acid (PLLA), especially to increase its toughness without sacrificing too much of its original strength. Besides of its long degradation time, PLLA is usually hard and brittle, which hinders its usage in medical applications, i.e., orthopedic and dental surgery. Some modifications, such as the addition of plasticizers or surfactants/compatibilizers, are usually required to improve its original properties. PDLLA can degrade quickly due to its amorphous structure, thus shortening the degradation time of PLLA/PDLLA blends. Blends of biodegradable poly- l-lactic acid (PLLA) and poly- dl-lactic acid (PDLLA) or polycaprolactone (PCL), in addition to a third component, the surfactant—a copolymer of ethylene oxide and propylene oxide, were prepared by blending these three polymers at various ratios using dichloromethane as a solvent. The weight percentages of PLLA/PDLLA (or PCL) blends were 100%/0%, 80%/20%, 60%/40%, 50%/50%, 40%/60%, 20%/80% and 0%/100%, respectively. Physical properties such as the crystalline melting point, glass transition point ( T g), phase behavior, degradation behavior, and other mechanical properties were characterized by thermogravimetric analysis, differential scanning calorimetry (DSC), infrared spectroscopy, gel permeation chromatography, and dynamic mechanical analysis (DMA). DSC data indicate that PLLA/PDLLA blends without the surfactant had two T g ’ s. With the addition of the surfactant, there was a linear shift of the single T g as a function of composition, with lower percentages of PLLA producing lower glass transition temperatures indicating that better miscibility had been achieved. DMA data show that the 40/60 PLLA/PDLLA blends without the surfactant had high elastic modulus and elongation, and similar results were observed after adding 2% surfactant into the blends. The 50/50 PLLA/PDLLA/2% surfactant blend had the highest elastic modulus, yield strength, and break strength compared with other ratios of PLLA/PDLLA/2% surfactant blends. The elongation at break of 50/50 PLLA/PDLLA was similar to that of PLLA. Again, the elongation at break of 50/50 PLLA/PDLLA/2% surfactant was almost 1.2–1.9 times higher than that of 50/50 PLLA/PDLLA and PLLA. Elongation of PLLA increased with the addition of PCL, but the strength decreased at the same time. In conclusions, adding PDLLA and surfactant to PLLA via solution-blending may be an effective way to make PLLA tougher and more suitable to use in orthopedic or dental applications.

Influence of preparation conditions on acyclovir-loaded poly-d,l-lactic acid nanospheres and effect of PEG coating on ocular drug bioavailability.

The evaluation of nanosphere colloidal suspensions containing acyclovir as potential ophthalmic drug delivery systems was carried out. The influence of polymer molecular weight and type and concentration of various surfactants on nanosphere properties was studied. The ocular pharmacokinetics of acyclovir-loaded nanoparticles was evaluated in vivo and compared with an aqueous suspension of the free drug. Nanospheres were made up of poly-d,l-lactic acid (PLA). The colloidal suspension was obtained by a nanoprecipitation process. The surface properties of PLA nanospheres were changed by the incorporation of pegylated 1,2-distearoyl-3-phosphatidylethanolamine. The mean size and zeta potential of the nanospheres were determined by light scattering analysis. The acyclovir loading capacity and release were also determined. In vivo experiments were carried out on male New Zealand rabbits. The ocular tolerability of PLA nanospheres was evaluated by a modified Draize test. The aqueous humor acyclovir levels were monitored for 6 h to determine the drug's ocular bioavailability for the various formulations. A reduction of the mean size and a decrease of the absolute zeta potential of PLA nanospheres resulted from increasing the surfactant concentration. The higher the polymer molecular weight, the smaller the nanosphere mean size. PEG-coated and uncoated PLA nanospheres showed a sustained acyclovir release and were highly tolerated by the eye. Both types of PLA nanospheres were able to increase the aqueous levels of acyclovir and to improve the pharmacokinetics profile, but the efficacy of the PEG-coated nanospheres was significantly higher than that of the simple PLA ones. PEG-coated PLA nanospheres can be proposed as a potential ophthalmic delivery system for the treatment of ocular viral infections.

Synthesis of Polyethylene Magnetic Nanoparticles

ABSTRACT Very low molecular weight polyethylene (average MW 700 g/mole) magnetic nanocomposite particles were synthesized by nonsolvent and temperature induced crystallization along with ultrasonication. The particles are further coated with poly dl-lactic acid to functionalize the polyethylene particles for biomedical applications. A solvent-nonsolvent emulsion was made with polyethylene and surface modified iron oxide and was raised to very high temperature followed by rapid cooling. Decalin and octamethylcyclotetrasiloxane (OMCTS) were used as solvent and tetraglyme as nonsolvent. The synthesized particles were found to have two different types of morphology. Particles sizes can be varied depending on the choice of solvent, polymer concentration and amplitude of ultrasonication. The composite particles were characterized by scanning transmission electron microscopy. Magnetic properties of the composite particles were also studied.

Bone response to polymers based on poly-lactic acid and having different degradation times.

Authors studied two degradable and resorbable polymers derived from lactic acid: poly-L-Lactic acid (PLLA), with a relatively long time of degradation (longer than 6 months, PL10 Purac NL); poly-DL-Lactic acid (PDLLA), with a relatively short time of degradation (shorter than 6 months, PDL Purac NL). The animal species was the young adult New Zealand White rabbit. The in-vivo study was performed by implantation of small cylinders of 10 x 3 mm in size (length x diameter) in the distal metaepiphysis of the femur; 34 cylinders have been implanted. Retrievals of PLLA specimens took place at 3, 6, 9, 12 and 24 months; for PDLLA specimens at 1, 2, 4 months. Polarized light microscopy of undecalcified tissue sections was performed. The analysis for PLLA and PDLLA has shown a favorable response of bone tissue: alterations in the bone repair, growth and remodeling have not been observed. PLLA is persistent at the times studied; there is never a tight apposition between bone and PLLA implant and an intervening fibrous layer has often been observed. PDLLA is not persistent at the times studied and it degrades quite fast; bone repair of the empty implantation's hole occurs by bony growth from the endosteal trabeculae. The newly formed bone covers the hole's walls with an elongation parallel to them. For both polymers, whether the degradation is fast or slow, the material's substitution by newly formed bone never starts from the walls of the implantation hole. Only after the complete disappearance of the polymeric material newly formed bone begins to fill the hole.

Controlled release of vancomycin from biodegradable microcapsules

Poly D,L-lactic acid (PLA) and its copolymers with glycolide PLGA 90:10 and 70:30 were polymerized under various conditions to yield polymers in the molecular weight range 12000-40000 daltons, as determined by gel permeation chromatography. Vancomycin hydrochloride was the hydrophilic drug of choice for the treatment of methicillin resistant Staphyloccoccal infections. It was microencapsulated in the synthesized polymers using water-oil-water (w/o/w) double emulsion and solvent evaporation. The influence of microcapsule preparation medium on product properties was investigated. An increase in polymer-to-drug ratio from 1:1 to 3:1 caused an increase in the encapsulation efficiency (i.e. from 44-97% with PLGA). An increase in the emulsifier (PVA) molecular weight from 14-72 kD caused an increase in encapsulation efficiency and microcapsule size. The in vitro release of vancomycin from microcapsules in phosphate buffer saline (pH 7.4) was found to be dependent on molecular weight and copolymer type. The kinetic behaviour was controlled by both diffusion and degradation. Sterilization with 60Co (2.5 Mrad) also affected the degradation rate and release profiles. Degradation of microcapsules could be seen by scanning electron microscopy, by the increase in the release rate from PLA and by the decrease in the Tg values of microcapsules. In vitro bactericidal effects of the microcapsule formulations on S.aureus were determined with a special diffusion cell after the preparations had been sterilized, and were found to have bactericidal effects lasting for 4 days.

Salt and cosolvent effects on ionic drug loading into microspheres using an O/W method

Salt effects on aqueous solubility and microsphere entrapment efficiency of a model ionic drug (quinidine sulfate) were studied. Poly- d,l-lactic acid (PLA) microspheres were prepared using an O/W solvent evaporation method with various electrolytes added in different concentrations to the aqueous phase. Salts affect microsphere drug loading by changing the aqueous solubility of both the drug and the organic solvent (dichloromethane, DCM). Quinidine sulfate solubility was depressed by either a common ion effect (Na 2SO 4) or by formation of new, less soluble drug salts (e.g., bromide, perchlorate, thiocyanate) for which solubility products ( K sp) were estimated. Inorganic salts depress DCM aqueous solubility to different extents as described by the Hofmeister series. NaClO 4 and NaSCN depressed drug solubility to the highest extent, resulting in microspheres with high drug loading (e.g., >90%). Other salts such as Na 2SO 4 did not depress quinidine sulfate solubility to the same extent and did not improve loading. The use of a cosolvent (ethanol) in the organic phase improved microsphere drug loading and resulted in a uniform microsphere drug distribution with smooth release profiles.

Oral immunization with size-purified microsphere beads as a vehicle selectively induces systemic tolerance and sensitization

Oral administration of antigens has long been recognized as a method to prevent or delay the onset of diseases associated with untoward immune responses to self and non-self antigens. Although oral administration of antigens offers a convenient way to induce systemic tolerance, its therapeutic potential has been seriously limited by the fact that it requires repeated feeding of a large amount of antigens and that it may deteriorate ongoing autoimmune diseases when autoantigens are employed. We have previously shown that orally administered poly- D, L-lactic acid (PDLLA) microspheres containing an antigen were selectively distributed to Peyer’s patches (PP) and systemic lymphoid tissues according to their diameter and then released the antigen over a long period of time. We now report that a single dose of intragastric immunization with a PDLLA microsphere 7–10 μm in diameter and containing 2 mg of OVA was as effective as 100 mg of water soluble OVA to suppress OVA-specific IgG and DTH response. This was associated with a large increase of Interferon-γ production by PPT cells stimulated with an antigen and a small increase in secretory IgA specific to OVA. In contrast, administration of an antigen encapsulated in microspheres 3–4 μm in diameter led to an enhanced OVA-specific IgG response and no significant increase in OVA-specific secretory IgA. Thus, by utilizing microspheres of an appropriate diameter as a vaccination vehicle, we were able to selectively induce both systemic tolerance and sensitization by oral ingestion of single low dose of an antigen.

Effect of preparation conditions on morphology and release profiles of biodegradable polymeric microspheres containing protein fabricated by double-emulsion method

We have investigated the key parameters to fabricate PDLLA (Poly( dl-lactic acid)), PDLLGA (Poly( dl-lactic-co-glycolic acid) 65 : 35 and blends of PDLLGA 65 : 35 and PEG (Poly(ethylene glycol)) microspheres containing bovine serum albumin (BSA) as a model protein using the double-emulsion (water-in-oil-in-water) solvent extraction/evaporation method. The release profiles of microspheres were investigated at 22°C in order to develop controlled release devices for marine fishes in tropical area. Various factors that influence the size of microspheres, encapsulation efficiency, initial release, morphology and release profiles of microspheres, and BSA distribution within microspheres have been investigated. These factors include preparation temperature, solvent removal rate, volume ratio of oil phase to internal water phase, and polymer concentration. Microspheres fabricated at a low volume ratio of oil phase to internal water phase and a low polymer concentration tend to have a large surface area, a low bulk density, resulting in a high initial burst and a fast release of BSA. Fabrication temperature heavily affects solvent extraction/evaporation and mechanism of phase-inversion. The microspheres fabricated at 4 and 38°C yield the highest encapsulation efficiency (52.0–48.0%) and lowest initial BSA release (18.8–20.0%), while microspheres produced at 22°C have the lowest encapsulation efficiency and highest initial burst. This interesting phenomenon is due to the fact that different phase-inversion paths occur when preparation temperature varies. Nucleation growth and spinodal decomposition dominate the skin formation at low preparation temperatures, while evaporation-driven skin formation takes place at high preparation temperatures. The relationship between the release profile and the rate of continuous water-phase addition is extremely complicated. Slow demixing dominates the interface skin formation at low continuous water-phase addition rates and results in fine porous skin structure, while rapid demixing dominates at high continuous water-phase addition rates and also leads to microspheres with a porous skin. Thus both have high initial bursts and fast release rates. A continuous water-phase addition of 3 ml/min may yield the microspheres having a low initial burst and a slow release rate.

Synthesis and characterization of biodegradable hydrophobic-hydrophilic hydrogel networks with a controlled swelling property

A biodegradable polymer network hydrogel system with both hydrophilic and hydrophobic components was synthesized and characterized. The hydrophilic and hydrophobic components were dextran and poly(D,L)lactic acid (PDLLA), respectively. These two polymers were chemically modified for incorporating unsaturated groups for subsequent UV crosslinking to generate a hydrogel with a three-dimensional network structure. The effects of the reaction conditions on the synthesis of a dextran derivative of allyl isocyanate (dex-AI) were studied. All newly synthesized materials were characterized by Fourier transform infrared and NMR. The swelling property of the hydrogels was studied in buffer solutions of different pHs. The results of this study showed that a wide-range swelling property was obtained by changes in the dex-AI/PDLLA composition ratio, the type and degree of unsaturated groups incorporated into dextran, and the UV photocrosslinking time. The solvent extraction effect on the swelling property of the hydrogels was also studied. © 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 38: 2392–2404, 2000