Hyperbranched Polymers as Drug Carriers: Microencapsulation and Release Kinetics

The aim of this work was to study the feasibility of hyperbranched polymers as drug carriers by employing different microparticle formation methods and the influence of loading methods on release kinetics. Commercially available hyperbranched polyester (Perstorp) and three polyesteramides (DSM) were loaded with the pharmaceutical acetaminophen. The gas antisolvent precipitation (GAS), the coacervation, and the particles from gas saturated solutions (PGSS) are among conventional processes that were used to prepare microparticles of drug-loaded hyperbranched polyesters for the first time. For preparing solid dispersions of drug-loaded hyperbranched polyesteramides the solvent method was applied. Infrared (IR) and differential thermal analysis (DTA) studies suggest that acetaminophen is partly dissolved in the polymer matrix and partly crystallized outside the polymer matrix. For acetaminophen-loaded polyesters prepared by the GAS method, the presence of free drugs is predominant when compared to microparticles prepared by the coacervation method. This event disappears for microparticles prepared by the PGSS method. Moreover, the release of drug from drug-loaded Bol-GAS is biphasic, where the initial burst (48%), indicating the presence of unincorporated drugs, is followed by a slow-release phase, suggesting the diffusion of drug through polymer matrices. The release of drugs from drug-loaded Bol-PGSS do not show this behavior since the drug is better dissolved or dispersed in polymer matrices. In the case of drug-loaded polyesteramides, coevaporates prepared from 3 hyperbranched structures (H1690, H1200, and H1500) using the solvent method result in different release kinetics. The hydrophobic characteristic of hyperbranched polyesteramide H1500 shows the biphasic release kinetic whereas the drug released from hydrophilic matrices H1690 and H1200 exhibits fast release comparable to that of pure drug.     

Preparation, characterization and in vitro cytotoxicity of indomethacin-loaded PLLA/PLGA microparticles using supercritical CO(2) technique.

In this work, indomethacin-loaded poly(l-lactic acid)/poly(lactide-co-glycolide) (IDMC-PLLA/PLGA) microparticles were prepared using solution-enhanced dispersion by supercritical fluids (SEDS) technique in an effort to obtain alternative IDMC formulation for drug delivery system. Surface morphology, particle size and particle size distribution, drug encapsulation efficiency, drug release kinetics, in vitro cytotoxicity and the cellular uptake of drug-loaded microparticles were investigated. The drug-loaded microparticles exhibited sphere-like shape and small particle size with narrow particle size distribution. IDMC was amorphously dispersed within the PLLA/PLGA matrix after the SEDS process. In vitro release studies revealed that the drug-loaded microparticles substantially enhanced the dissolution rate of IDMC compared to the free IDMC, and demonstrated a biphasic drug release profile. In vitro cytotoxicity assays indicated that drug-loaded microparticles possessed longer sustained inhibition activity on proliferation of the non-small-cell lung cancer A549 cell lines than did free IDMC. Fluorescence microscopy and transmission electron microscopy identified the phagocytosis of drug-loaded microparticles into the A549 cells and characteristic morphology of cell apoptosis such as the nuclear aberrations, condensation of chromatin, and swelling damage in mitochondria. These results collectively suggested that IDMC-PLLA/PLGA microparticles prepared using SEDS would have potentials in anti-tumor applications as a controlled drug release dosage form without harmful organic solvent residue.     

In-process crystallization of acidic drugs in acrylic microparticle systems: influence of physical factors and drug-polymer interactions

Emulsion-solvent evaporation is an established method to fabricate amorphous drug-loaded microparticles. In some cases, however, the encapsulated drug is present in its crystalline form, which can affect drug release and negatively impact on other characteristics of the final product. This work aimed to investigate the factors that are responsible for the formation (and inhibition) of drug crystals in modified-release microparticles. Five acidic drugs were encapsulated into Eudragit S or Eudragit L microparticles. Drug crystallinity was observed when indometacin and naproxen were encapsulated, while crystallization was not observed in the case of ketoprofen, salicylic acid, or paracetamol (acetaminophen). All drug-loaded microparticles had single glass transition temperature (T(g) ) intermediate between the T(g) of the drug and that of the polymer. The drop in T(g) in the case of the paracetamol-loaded particles was higher than predicted from the Gordon-Taylor equation, indicating that paracetamol was acting as a plasticizer in this system. After melt quenching in the presence of the Eudragit polymers, the crystallization of paracetamol was inhibited. The ratio of drug to polymer in the microparticles was the major determinant of drug crystallization, as was the solubility of the drug in the processing solvent. This work confirms that drug crystallization is a complex phenomenon, and that drug-polymer molecular interactions play a role in the inhibition of drug crystallization.     

Studies on the in vitro release characteristics of ibuprofen-loaded polystyrene microparticles

Ibuprofen-loaded polystyrene microparticles were prepared by the emulsion-solvent evaporation process from an aqueous system. The effects of different parameters on the drug content and on the release of the drug from the microparticles were investigated. The drug content, in all the formulations, was less than the theoretical drug loading. The lower drug content was due to drug partitioning to the external aqueous phase during formulation. Statistical analysis revealed that the variation in the concentrations of the emulsion stabilizer and the organic disperse phase volume did not significantly alter the release of the drug. Although an increase in drug loading increased drug release from the microparticles, a biphasic linear relationship was observed between the time required for 50% drug release and the drug loading. The effect of size of the microparticles on drug release was more important for the low drug-loaded microparticles than that for the high drug-loaded microparticles. Such release behaviour from the microparticles was explained on the basis of the morphological structure of the microparticles.     

Studies on the in vitro release characteristics of ibuprofenloaded polystyrene microparticles

Ibuprofen-loaded polystyrene microparticles were prepared by the emulsionsolvent evaporation process from an aqueous system. The effects of different parameters on the drug content and on the release of the drug from the microparticles were investigated. The drug content, in all the formulations, was less than the theoretical drug loading. The lower drug content was due to drug partitioning to the external aqueous phase during formulation. Statistical analysis revealed that the variation in the concentrations of the emulsion stabilizer and the organic disperse phase volume did not significantly alter the release of the drug. Although an increase in drug loading increased drug release from the microparticles, a biphasic linear relationship was observed between the time required for 50% drug release and the drug loading. The effect of size of the microparticles on drug release was more important for the low drug-loaded microparticles than that for the high drug-loaded microparticles. Such release behaviour from the microparticles was explained on the basis of the morphological structure of the microparticles.     

Biodegradable microparticulate system of captopril

Albumin microparticles have found many applications in diagnosis and treatment in recent years and more than 100 diagnostic agents and drugs have been incorporated into albumin microparticles. In the present study, bovine serum albumin (BSA) based microparticles bearing captopril were prepared by an emulsification-heat stabilization technique. Four batches of microparticles with varying ratio of drug and polymer were prepared. The prepared microparticles were studied for drug loading, particle size distribution, in vitro release characteristics, in vivo tissue distribution study and stability studies. The microparticles had mean diameter between 2 and 11 microm of which more than 70% were below 5 microm and incorporation efficiency of 41-63% was obtained. In vitro release profile for formulations containing captopril-loaded albumin microparticles with heat stabilizing technique shows slow controlled release up to 24 h. The in vivo result of drug-loaded microparticles showed preferential drug targeting to liver followed by lungs, kidneys and spleen. Stability studies showed that maximum drug content and closest in vitro release to initial data were found in the formulation stored at 4 degrees C. In the present study, captopril-loaded BSA microparticles were prepared and targeted to various organs to a satisfactory level and were found to be stable at 4 degrees C.     

Effect of poly(lactide-co-glycolide) molecular weight on the release of dexamethasone sodium phosphate from microparticles

The objective of this study was to investigate the effect of poly(lactide-co-glycolide) (PLGA) molecular weight (Resomer RG 502H, RG 503H, and RG 504H) on the release behavior of dexamethasone sodium phosphate-loaded microparticles. The microparticles were prepared by three modifications of the solvent evaporation method (O/W-cosolvent, O/W-dispersion, and W/O/W-methods). The encapsulation efficiency of microparticles prepared by the cosolvent- and W/O/W-methods increased from approximately 50% to >90% upon addition of NaCl to the external aqueous phase, while the dispersion method resulted in lower encapsulation efficiencies. The release of dexamethasone sodium phosphate from PLGA microparticles (>50 microm) was biphasic. The initial burst release correlated well with the porosity of the microparticles, both of which increased with increasing polymer molecular weight (RG 504H > 503H > 502H). The burst was also dependent on the method of preparation and was in the order of dispersion method > WOW method > consolvent method. In contrast to the higher molecular weight PLGA microparticles, the release from RG 502H microparticles prepared by cosolvent method was not affected by volume of organic solvent (1.5-3.0 ml) and drug loading (4-13%). An initial burst of approximately 10% followed by a 5-week sustained release phase was obtained. Microparticles with a size <50 microm released in a triphasic manner; an initial burst was followed by a slow release phase and then by a second burst.     

Encapsulation of lipophilic drugs within enteric microparticles by a novel coacervation method

Enteric microparticles were prepared by a novel microencapsulation method in order to improve the oral bioavailability of lipophilic drugs. This method involved the addition of an aqueous polymer solution to an organic enteric polymer solution containing lipophilic drugs. In contrast to classical coacervation microencapsulation methods, the drugs were initially also dissolved and not dispersed in the organic polymer solution. The hydrophilic polymer (hydroxypropyl methylcellulose (HPMC), hydroxypropyl cellulose (HPC) and Poloxamer 407) was dissolved in the aqueous phase and acted as a stabilizer for the coacervate droplets, preventing their coalescence and leading to the formation of enteric microparticles. The size of the enteric microparticles decreased with higher concentrations of the hydrophilic polymers, a higher pH of the aqueous polymer solution, a higher content of carboxyl groups of the enteric polymer and with better polymer solvents. Amide-containing lipophilic drugs, such as carbamazepine, lidocaine and cyclosporine A, were successfully encapsulated in the enteric microparticles in a non-crystalline state and were physically stable for 5 months. The high solubility of carbamazepine in the enteric polymer (>30%, w/w), a high partition coefficient between polymer-rich/-poor regions and strong drug/polymer interactions contributed to the high drug encapsulation efficiency (90%, w/w). In contrast, carboxyl-containing drugs (indomethacin, ibuprofen) and hydroxyl-containing drug (17beta-estradiol hemihydrate) crystallized inside or outside the polymeric matrix due to their low solubility in the enteric polymer.     

Biphasic release characteristics of dual drug-loaded alginate beads

The dual drug-loaded alginate beads simultaneously containing drug in inner and outer layers were prepared by dropping plain (single-layered) alginate beads into CaCl₂ solution. The release characteristics were evaluated in simulated gastric fluid for 2 h followed by intestinal fluids thereafter for 12 h. The surface morphology and cross section of dual drug-loaded alginate beads was also investigated using scanning electron microscope (SEM). The poorly water-soluble ibuprofen was chosen as a model drug. The surface of single-layered and dual drug-loaded alginate beads showed very crude and roughness, showing aggregated particles, surface cracks and rough crystals. The thickness of dual drug-loaded alginate beads surrounded by outer layer was ranged from about 57 to 329μm. The distinct chasm between inner and outer layers was also observed. In case of single-layered alginate beads, the drug was not released in gastric fluid but was largely released in intestinal fluid. However, the release rate decreased as the reinforcing Eudragit^® polymer contents increased. When the plasticizers were added into polymer, the release rate largely decreased. The release rate of dual drug-loaded alginate beads was stable in gastric fluid for 2 h but largely increased when switched in intestinal fluid. The drug linearly released for 4 h followed by another linear release thereafter, showing a distinct biphasic release characteristics. There was a difference in the release profiles between single-layered and dual drug-loaded alginate beads due to their structural shape. However, this biphasic release profiles were modified by varying formulation compositions of inner and outer layer of alginate beads. The release rate of dual drug-loaded alginate beads slightly decreased when the outer layer was reinforced with Eudragit^® RS100 polymers. In case of dual drug-loaded alginate beads with polymer-reinforced outer layer only, the initial amount of drug released was low but the initial release rate (slope) was higher due to more swellable inner cores when compared to polymer-reinforced inner cores. The current dual drug-loaded alginate beads may be used to deliver the drugs in a time dependent manner.     

Fabrication of drug-loaded biodegradable microcapsules for controlled release by combination of solvent evaporation and layer-by-layer self-assembly

The initial burst release of drug from polymer microparticles remains an unsolved problem. Here, we deposited polysaccharides on drug-loaded microspheres using layer-by-layer self-assembly to produce core-shell microparticles for sustained drug release. The ibuprofen (IBU)-loaded poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) microparticles were fabricated by conventional solvent evaporation. The processing parameters, such as pH of water phase, drug/polymer ratio, polymer type, and emulsifier concentration, were optimized according to the encapsulation efficiency and drug loading as pH 4.0, drug/polymer ratio=10/50 (wt), HV in PHBV=6wt.%, and PVA concentration=1% (w/v). The multilayer shells of chitosan (CHI)/sodium alginate (ALG) and poly(diallyldimethylammonium chloride) (PD)/sodium poly(styrenesulfonate) (PSS) were formed on the IBU-loaded PHBV microparticles using layer-by-layer self-assembly. The in vitro release experiments revealed that, as for the microparticles with three CHI/ALG bilayer shells, the initial burst release of IBU from the microparticles was significantly suppressed and the half release time was prolonged to 62h from 1h for the microparticles without coverage. The compact CHI/ALG multilayer film was observed with an atomic force microscopy (AFM) due to the matched distance of charges along the CHI chain and those along the ALG chains. The present combination for encapsulating drug-loaded microparticles demonstrates an effective way to prolong the drug release with reduced initial burst.     

Nanocapsule@xerogel microparticles containing sodium diclofenac: a new strategy to control the release of drugs

The aim of this work was to evaluate the potentiality to control the drug release of a new architecture of microparticles organized at the nanoscopic scale by assembling polymeric nanocapsules at the surface of drug-loaded xerogels. Xerogel was prepared by sol-gel method using sodium diclofenac, as hydrophilic drug model, and coated by spray-drying. After coating, the surface areas decreased from 82 to 28 m(2)/g, the encapsulation efficiency was 71% and SEM analysis showed irregular microparticles coated by the nanocapsules. Formulation showed satisfactory gastro-resistance presenting drug release lower than 3% (60 min) in acid medium. In water, the pure drug dissolved 92% after 5 min, uncoated drug-loaded xerogel released 60% and nanocapsule coated drug-loaded xerogel 36%. After 60 min, uncoated drug-loaded xerogel released 82% and nanocapsule coated drug-loaded xerogel 62%. In conclusion, the new system was able to control the release of the hydrophilic drug model.     

Combination of adsorption by porous CaCO3 microparticles and encapsulation by polyelectrolyte multilayer films for sustained drug delivery

Combination of adsorption by porous CaCO(3) microparticles and encapsulation by polyelectrolyte multilayers via the layer-by-layer (LbL) self-assembly was proposed for sustained drug release. Firstly, porous calcium carbonate microparticles with an average diameter of 5 microm were prepared for loading a model drug, ibuprofen (IBU). Adsorption of IBU into the pores was characterized by ultraviolet (UV), infrared (IR), thermogravimetric analysis (TGA), Brunauer-Emmett-Teller (BET) experiment and X-ray diffraction (XRD). The adsorbed IBU amount Gamma was 45.1mg/g for one-time adsorption and increased with increasing adsorption times. Finally, multilayer films of protamine sulfate (PRO) and sodium poly(styrene sulfonate) (PSS) were formed on the IBU-loaded CaCO(3) microparticles by the layer-by-layer self-assembly. Amorphous IBU loaded in the pores of the CaCO(3) microparticles had a rapider release in the gastric fluid and a slower release in the intestinal fluid, compared with the bare IBU crystals. Polyelectrolyte multilayers assembled on the drug-loaded particles by the LbL reduced the release rate in both fluids. In this work, polymer/inorganic hybrid core-shell microcapsules were fabricated for controlled release of poorly water-soluble drugs. The porous inorganic particles are useful to load drugs in amorphous state and the polyelectrolyte multilayer films coated on the particle assuage the initial burst release.     

Controlled release of dual drug-loaded hydroxypropyl methylcellulose matrix tablet using drug-containing polymeric coatings.

A dual drug-loaded hydroxypropylmethylcellulose (HPMC) matrix tablet simultaneously containing drug in inner tablet core and outer coated layer was formulated using drug-containing aqueous-based polymeric Eudragit RS30D dispersions. Effects of coating levels, drug loadings in outer layers, amount and type of five plasticizers and talc concentration on the release characteristics were evaluated on the characteristics in simulated gastric fluid for 2 h followed by a study in intestinal fluids. Melatonin (MT) was selected as a model drug. The surface morphology of dual drug-loaded HPMC tablets using scanning electron microscope (SEM) was smooth, showing the distinct coated layer with about 75-microm coating thickness at the 15% coating level. Unlike the uncoated and conventionally coated HPMC tablet, the dual drug-loaded HPMC matrix tablet gave a biphasic linear release, showing a zero-order for 4 h (first) followed by another zero-order release when fitted using linear regression (r(2) = 0.99). As the coating levels (15, 25%) increased, the release rate was further decreased. The biphasic release profiles of dual drug-loaded HPMC matrix tablet was unchanged except when 25% coating level containing 0.5% drug concentration was applied. As the drug concentration in polymeric coating dispersion increased (0.25-1.0%), the amount of drug released increased. The time for the first linear release was also advanced. However, the biphasic release pattern was not changed. The biphasic release profiles of dual drug-loaded HPMC matrix tablet were highly modified, depending on the amount and type of five plasticizers. Talc (10-30%) in coating dispersion as an anti-sticking material did not affect the release profiles. The current dual drug-loaded HPMC matrix tablet, showing biphasic release profiles may provide an alternative to deliver drugs with circadian rhythmic behaviors in the body but needs to be further validated in future in human studies. The dual drug-loaded coating method is also interesting for the modified release of poorly water-soluble drugs because solubilizers and other additives can be added in drug-containing polymeric coating dispersions.     

Drug release testing methods of polymeric particulate drug formulations

The long-term controlled delivery of drugs has been successfully achieved by biodegradable polymeric particulate systems. The drug release testing method is important for the characterization of dosage form performance under in vitro standardized conditions and can provide insight into the in vivo performance of the drug product. In vitro drug release testing methods for polymeric particulate systems are classified into sample and separate (SS), dialysis, and continuous flow (CF) methods. In the SS method, the drug-loaded microparticles are suspended in a vessel and the samples for the analysis are obtained by separating the particles using filtration or centrifugation. The dialysis method physically separates microparticles from the release media by a membrane, which eliminates the undesired loss of particles during sample preparation and handling. The CF method uses apparatus consisted of flow-through cell that holds the sample, pump and water bath in closed or open ends system. In this method, the release media is continuously circulated through a cell containing drug-loaded microparticles. This review summarizes the principles of the drug release testing methods and discusses their characteristics with the recent research results.     

Preparation of preformed porous PLGA microparticles and antisense oligonucleotides loading

The objective of this study was to load preformed highly porous microparticles with drug. The microparticles were prepared by a modified multiple emulsion (w/o/w) solvent evaporation method with the addition of pore formers (NaCl into the internal aqueous phase or of glycerol monooleate to the poly(lactide-co-glycolide) (PLGA) polymer phase). The drug-free solidified microparticles were then washed with either water (for NaCl) or hexane (for glycerol monooleate) to extract the pore formers. The drug was then loaded into the preformed porous microparticles by incubation in aqueous drug solutions followed by air- or freeze-drying. The drug was strongly bound to the polymeric surface with air-dried microparticles. A biphasic drug release with an initial rapid release phase (burst effect) was followed by a slower release up to several weeks. The initial burst was dependent on the drug loading and could be significantly reduced by wet (non-aqueous) temperature curing.     

Time-engineeringed biphasic drug release by electrospun nanofiber meshes

A drug-loaded nanofiber mesh which could achieve time-engineeringed biphasic release was fabricated through sequential electrospinning. The drug to polymer ratio of each single mesh was allocated and designed before the tri-layered meshes were created. The resultant meshes had the following construction: (i) the first drug-loaded mesh (top side), (ii) the second drug-loaded mesh (second side), and (iii) the third drug-loaded mesh (bottom side). The drug release speed and duration were controlled by designing morphological features of the electrospun meshes such as the fiber diameter and mesh thickness. An in vitro release experiment revealed that the tri-layered construction with distinct morphological features of each component mesh can provide biphasic drug release. The time-engineeringed dual release system using the multilayered electrospun nanofiber meshes was proved to be a useful formulation when achieving controlled drug release at different times.     

Protective effect of drug delivery systems against the enzymatic degradation of dermally applied DNAzyme

Yet, no standardized test method for drug release measurements from PLGA-based microparticles has been generally agreed on, or described by the regulatory authorities. Often, perfect sink conditions are provided in vitro to avoid artificial drug saturation effects. However, the maintenance of such conditions might strongly affect PLGA degradation. The involved physicochemical processes are complex and the potential impact of perfect sink conditions is not yet well understood. Differently sized, highly porous, carbamazepine- and ibuprofen-loaded PLGA microparticles were prepared by a W/O/W emulsion solvent extraction/evaporation technique. The initial drug loading was intentionally low (3-4%) so that the two drugs were molecularly dispersed within the polymeric matrices (monolithic solutions). This was important to be able to exclude potential limited drug solubility effects on the resulting release kinetics. Drug release into phosphate buffer pH 7.4 was measured under perfect sink conditions. SEC, DSC and SEM were used to characterize polymer degradation. The decrease in the average polymer molecular weight, glass transition temperature as well as changes in the inner and outer morphology of the PLGA microparticles were strongly affected by the bulk fluid's volume. In the case of the poorly water-soluble drug carbamazepine, much lower "microparticle mass:phosphate buffer volume" ratios were required to maintain perfect sink conditions, resulting in stable pH values within the bulk fluid, slower PLGA degradation and, thus, lower drug release rates. Thus, great care has to be taken when defining the conditions for in vitro drug release measurements from PLGA-based microparticles, avoiding potentially artificial conditions for polymer degradation.     

Development of pH- and time-dependent oral microparticles to optimize budesonide delivery to ileum and colon

A microparticulate system consisting of non-enzymatically degrading poly(dl-lactide-co-glycolide) (PLGA) core and delivering budesonide site specifically to distal ileum and colon was developed. Budesonide-loaded microparticles were fabricated using solvent evaporation technique and formulation variables studied included different molecular weight grades of PLGA polymer as well as concentration of polymer, surfactant and drug. Eudragit S-100, an enteric polymer, was then used to form a coating on the surface of budesonide-loaded PLGA microparticles for site specific delivery to the distal ileum and colon. Budesonide-loaded PLGA microparticles prepared from various formulation parameters showed mean encapsulation efficiencies ranging between 50% and 85% and mean particle size ranging between 10 and 35mum. In vitro release kinetics studies showed a biphasic release pattern with an initial higher release followed by a slower drug release. Increasing polymer and surfactant concentrations exhibited sharply contrasting drug release profiles, with increasing polymer concentrations resulting in a lower drug release and vice versa. The budesonide-loaded PLGA microparticles coated with Eudragit S-100 coating showed a decrease in entrapment efficiency with an accelerated in vitro drug release. Moreover, complete retardation of drug release in an acidic pH, and, once the coating layer of enteric polymer was dissolved at higher pH (7.4 and 6.8), a controlled release of the drug from the microparticles were observed. From the results of this investigation, the application of double microencapsulation technique employing PLGA matrix and Eudragit S-100 coating shows promise for site specific and controlled delivery of budesonide in Crohn's disease.     

Drug distribution in enteric microparticles

The aim of this study was to assess the distribution of three fluorescent drug or drug-like molecules in enteric microparticles. Microparticles were prepared using the pH-responsive methylmethacrylate polymer Eudragit L by an emulsion solvent evaporation process. In the process drug and polymer are dissolved in ethanol, and dispersed in a liquid paraffin external phase using sorbitan sesquioleate as stabiliser. The incorporation and distribution of riboflavin, dipyridamole and acridine orange into these microparticles were investigated using confocal laser scanning microscopy (CLSM). The influence of the physicochemical properties of the molecules (solubility in the inner phase, partition coefficient [ethanol/paraffin]) on the distribution, encapsulation efficiency and pH-responsive dissolution behaviour of the microparticles were examined. The drug that tended to partition in ethanol rather than liquid paraffin (riboflavin) was efficiently encapsulated and evenly distributed. In contrast, compounds which partitioned in favour of the liquid paraffin localised towards the surface of the microparticles and exhibited lower encapsulation efficiency (dipyridamole and acridine orange). All three sets of drug-loaded microparticles showed a limited release in acid (<10% release); drug distribution appeared to have a minimum effect on drug release. This microparticle technology has the potential to provide effective enteric drug release with a wide variety of molecules.     

The effect of solvent removal conditions on performance and release property of protein-loaded microparticles

This study was designed to investigate the influence of solvent removal conditions on the performance and release properties of protein-loaded poly(epsilon-caprolactone) microparticles. The microparticles were prepared by the coacervation method in three different conditions. The effects of vacuum pressure, fabrication temperature and evaporation time on the crystallinity, surface morphology, particle size as well as the yield of microparticles, encapsulation efficiency of BSA and in vitro release property were investigated. There was no significant difference in the size of microparticles prepared by varying the vacuum pressure and temperature. Similar results were obtained for the production yield of microparticles and the loading efficiency of protein in these microparticles. However, accelerating the evaporation rate of solvent significantly reduced the crystallinity of polymer from 54.13 +/- 2.67% down to 44.64 +/- 2.17% (p < 0.05). The release of protein from the resulting microparticles was rapid, within 6 h, after which BSA was continuously and slowly released for up to 7 days. The protein release rate and polymer crystallinity possessed a good correlation (r = -0.951). This result indicated that the higher the crystallinity, the slower the release rate. In other words, change in vacuum pressure and temperature reduced the crystallinity of polymer, which was feasible for protein to release from amorphous domain in microparticles.