Formulation factors for preparing ocular biodegradable delivery system of 5-fluorouracil microparticles

Microparticles containing 5-fluorouracil (5-FU) were prepared using poly(dllactide-co-glycolide) with an oil-in-oil emulsion/solvent extraction technique. Particle characteristics including size distribution, 5-FU loading efficiencies, in vitro release and degradation were investigated. The dispersed phase was composed of PLG dissolved in dichloromethane, and the continuous phase was paraffin oil containing lecithin. 5-FU was successfully entrapped in the microparticles with trapping efficiencies up to 76%, loading level 10% w/v, and particle size 3 µm. Release profiles of 5-FU loaded microparticles were determined to follow a first-order-time relationship. An optimized preparation of 5-FU microparticles was achieved and was capable of controlling the release of 5-FU over 21 days with an in vitro delivery rate of 0.4 µg 5-FU/mg particles/ day in the study. Preliminary animal studies indicated that the 5-FU loaded microparticles as an ocular delivery system showed no ocular toxicity and no significant inflammatory response in rabbits for 2 months. The 5-FU loaded microparticles approach, with PLG, might be a potential for the application of long-term delivery of hydrophilic drugs in the eye.     

The stability of insulin in biodegradable microparticles based on blends of lactide polymers and polyethylene glycol

Insulin-loaded microparticles were produced from blends of poly(ethylene glycol) (PEG) with poly (L-lactide) (PLA) homopolymer and poly (DL-lactide co-glycolide) copolymers (PLG) using a water-in-oil solvent extraction method. The dispersed phase was composed of PLG/PEG or PLA/PEG dissolved in dichloromethane, and the continuous phase was methanol containing 10% PVP. Characteristics, including particle size distribution, insulin loading capacity and efficiencies, in vitro release, degradation and stability, were investigated. The stability of insulin associated with microparticles prepared using PEG and 50:50 PLG and PLA was analysed by HPSEC and quantified by peak area following incubation in PBS at 37 degrees C for up to 1 month. Insulin was successfully entrapped in the PLG/PEG and PLA/PEG microparticles with trapping efficiencies up to 56 and 48%, loading levels 17.8 and 10.6% w/w, and particle sizes 8 and 3 microm, respectively. The insulin-loaded PLG/PEG and PLA/PEG microparticles were capable of controlling the release of insulin over 28 days with in vitro delivery rates of 0.94 and 0.65 microg insulin/mg particles/day in the first 4 days and a steady release with rate of 0.4 and 0.43 microg insulin/mg particles/day over the following 4 weeks, respectively. Extensive degradation of the PLG/PEG microparticles also occurred over 4 weeks, whereas the use of PLA/PEG blends resulted in a stable microparticle morphology and much reduced fragmentation and aggregation of the associated insulin.     

Vibrio cholerae-loaded poly(DL lactide co-glycolide) microparticles

Vibrio cholerae (VC)-loaded microparticles were prepared using poly(DL lactide-co-glycolide) with a water-in-oil-in-water emulsion/solvent extraction technique. Particle characteristics including size distribution, VC-loading efficiencies, and in-vitro release pattern were investigated. The dispersed phase was PLG dissolved in dichloromethane, and the continuous phase was water containing PVP as a stabilizer with varied sodium chloride concentrations. VC was successfully entrapped in the microparticles with trapping efficiencies up to 97.8%, a loading level of 55.4 g/mg, and particle size of 3.8 microm. Using 10% w/v PVP with 5% w/v NaCl in the continuous phase resulted in a higher loading level (55.4 +/- 6.9 g/mg), loading efficiency (97.8%), core region content (25.7 +/- 1.9 g/mg) and lower surface content (6.2 +/- 0.9 g/mg) than without NaCl (loading content: 40.7 +/- 5.1 g/mg; loading efficiency 52.1%; core region content: 8.3 +/- 0.5 g/mg; surface content: 19.5 +/- 1.1 g/mg). A linear release profile from VC-loaded microparticles was found. A preliminary animal oral administration study indicated that the VC-loaded microparticles, as an oral delivery system, have shown effective immunogencity in rats for 2 months. The VC incorporation and physicochemical characterization data obtained in this study may be relevant in optimising the vaccine incorporation and delivery properties of these potential vaccine targeting carriers.     

Vibrio cholerae -loaded poly(DL lactide co-glycolide) microparticles

Vibrio cholerae (VC)-loaded microparticles were prepared using poly(DL lactide-co-glycolide) with a water-in-oil-in-water emulsion/solvent extraction technique. Particle characteristics including size distribution, VC-loading efficiencies, and in-vitro release pattern were investigated. The dispersed phase was PLG dissolved in dichloromethane, and the continuous phase was water containing PVP as a stabilizer with varied sodium chloride concentrations. VC was successfully entrapped in the microparticles with trapping efficiencies up to 97.8%, a loading level of 55.4 g/mg, and particle size of 3.8 #181;m. Using 10% w/v PVP with 5% w/v NaCl in the continuous phase resulted in a higher loading level (55.4 #45 6.9 g/mg), loading efficiency (97.8%), core region content (25.7 #45 1.9 g/mg) and lower surface content (6.2 #45 0.9 g/mg) than without NaCl (loading content: 40.7 #45 5.1 g/mg; loading efficiency 52.1%; core region content: 8.3 #45 0.5 g/mg; surface content: 19.5 #45 1.1 g/mg). A linear release profile from VC-loaded microparticles was found. A preliminary animal oral administration study indicated that the VC-loaded microparticles, as an oral delivery system, have shown effective immunogencity in rats for 2 months. The VC incorporation and physicochemical characterization data obtained in this study may be relevant in optimising the vaccine incorporation and delivery properties of these potential vaccine targeting carriers.     

Japanese encephalitis virus vaccine formulations using PLA lamellar and PLG microparticles

Japanese encephalitis virus (JEV)-loaded poly(lactide) (PLA) lamellar and poly(DL-lactide-co-glycolide) (PLG) microparticles were successfully prepared with low molecular weight PLA by the precipitate method and with 6% w/v PLG in the organic phase, 10% w/v PVP and 5% w/v NaCl in the continuous phase, by using a water-in-oil-in-water emulsion/solvent extraction technique, respectively. JEV was entrapped in the PLG microparticles by a solvent extraction technique with trapping efficiencies up to 98%, loading level 5.5% w/w, and mean particle size 3.8 microm. The distribution (%) of JEV on the PLG microparticles surface, outer layer, and core were 11.2, 41.7 and 46.4%, respectively. The cumulative release of JEV had an upper limit of approximately 58% of the JEV load at 24 days. The steady release rate was 1.33 microg JEV/mg microparticles/day of JEV release maintained for 24 days. The corresponding virus loading of the PLA lamellae is approximately 0.78% w/w and the loading efficiency (77.8%), JEV content (7.84 microg/mg), and yield (96.3%), respectively. The distribution (%) of JEV on the microparticles surface, outer layer, and core were 82.1, 13.3 and 2.2%, respectively. The live JEV challenge in mice test, in which mice received one dose of 20 mg JEV-loaded PLG microparticles, 20 mg JEV-loaded PLA lamellar in comparison with JEV or PBS solution, was evaluated after IP immunization of BALB/c mice. The study results show that the greatest survival was observed in the group of mice immunized with 20 mg JEV-loaded PLG microparticles and 20 mg JEV-loaded PLA microparticles group (80%). The JEV incorporation, physicochemical characterization data, and the animal results obtained in this study may be relevant in optimizing the vaccine incorporation and delivery properties of these potential vaccine targeting carriers.     

Patent Briefing

Japanese encephalitis virus (JEV)-loaded poly(lactide) (PLA) lamellar and poly(DL-lactide-co-glycolide) (PLG) microparticles were successfully prepared with low molecular weight PLA by the precipitate method and with 6% w/v PLG in the organic phase, 10% w/v PVP and 5% w/v NaCl in the continuous phase, by using a water-in-oil-in-water emulsion/solvent extraction technique, respectively. JEV was entrapped in the PLG microparticles by a solvent extraction technique with trapping efficiencies up to 98%, loading level 5.5% w/w, and mean particle size 3.8 #181;m. The distribution (%) of JEV on the PLG microparticles surface, outer layer, and core were 11.2, 41.7 and 46.4%, respectively. The cumulative release of JEV had an upper limit of ~ 58% of the JEV load at 24 days. The steady release rate was 1.33 #181;g JEV/mg microparticles/day of JEV release maintained for 24 days. The corresponding virus loading of the PLA lamellae is ~ 0.78% w/w and the loading efficiency (77.8%), JEV content (7.84 #181;g/mg), and yield (96.3%), respectively. The distribution (%) of JEV on the microparticles surface, outer layer, and core were 82.1, 13.3 and 2.2%, respectively. The live JEV challenge in mice test, in which mice received one dose of 20 mg JEV-loaded PLG microparticles, 20 mg JEV-loaded PLA lamellar in comparison with JEV or PBS solution, was evaluated after IP immunization of BALB/c mice. The study results show that the greatest survival was observed in the group of mice immunized with 20 mg JEV-loaded PLG microparticles and 20 mg JEV-loaded PLA microparticles group (80%). The JEV incorporation, physicochemical characterization data, and the animal results obtained in this study may be relevant in optimizing the vaccine incorporation and delivery properties of these potential vaccine targeting carriers.     

Inactive Vibrio cholerae whole-cell vaccine-loaded biodegradable microparticles: in vitro release and oral vaccination

An approach is proposed using Vibrio cholerae (VC)-loaded microparticles as oral vaccine delivery systems for improved vaccine bioavailability and increased therapeutic efficacy. The VC-loaded microparticles were prepared with 50:50 poly(DL-lactide-co-glycolide) (PLG), 75:25 poly(DL-lactide-co-glycolide) and poly(lactide acid) (PLA)/PEG blend copolymers by the solvent evaporation method. VC was successfully entrapped in three types of microparticles with loading efficiencies and loading levels as follows: 50:50 PLG systems: 97.8% and 55.4 +/- 6.9 micro g/mg; 75:25 PLG systems: 89.2% and 46.5 +/- 4.4 micro g/mg; PLA/PEG-blended systems: 82.6% and 53.7 +/- 5.8 micro g/mg. The different distributions of VC in the core region and on the surface were as follows: 50:50 PLG systems 25.7 +/- 1.9 and 6.2 +/- 0.9 micro g/mg; 75:25 PLG systems: 25.8 +/- 2.2 and 3.6 +/- 0.4 micro g/mg; PLA/PEG-blended systems: 32.4 +/- 2.1 and 5.2 +/- 1.0 micro g/mg, respectively. In vitro active release of VC was affected mainly by matrix type and VC-loaded location in microparticles. The therapeutic immunogenic potential of VC loaded with 50:50 PLG, 75:25 PLG and PLA/PEG-blended microparticles was evaluated in adult mice by oral immunization. Significantly higher antibody responses and serum immunoglobin Ig G, IgA and IgM responses were obtained when sera from both VC-loaded 75:25 PLG and PLA/PEG-blended microparticles immunized mice were titrated against VC. The most immunogenicity in evoking serum IgG, IgA and IgM responses was immunized by VC-loaded PLA/PEG-blended microparticles, and with VC challenge in mice, the survival rate (91.7%).     

Inactive Vibrio cholerae whole-cell vaccine-loaded biodegradable microparticles: in vitro release and oral vaccination

An approach is proposed using Vibrio cholerae (VC)-loaded microparticles as oral vaccine delivery systems for improved vaccine bioavailability and increased therapeutic efficacy. The VC-loaded microparticles were prepared with 50:50 poly(DL-lactide-co-glycolide) (PLG), 75:25 poly(DL-lactide-co-glycolide) and poly(lactide acid) (PLA)/PEG blend copolymers by the solvent evaporation method. VC was successfully entrapped in three types of microparticles with loading efficiencies and loading levels as follows: 50:50 PLG systems: 97.8% and 55.4 ± 6.9 µg/mg; 75:25 PLG systems: 89.2% and 46.5 ± 4.4?µg/mg; PLA/PEG-blended systems: 82.6% and 53.7 ± 5.8?µg/mg. The different distributions of VC in the core region and on the surface were as follows: 50:50 PLG systems 25.7 ± 1.9 and 6.2 ± 0.9?µg/mg; 75:25 PLG systems: 25.8 ± 2.2 and 3.6 ± 0.4?µg/mg; PLA/PEG-blended systems: 32.4 ± 2.1 and 5.2 ± 1.0?µg/mg, respectively. In vitro active release of VC was affected mainly by matrix type and VC-loaded location in microparticles. The therapeutic immunogenic potential of VC loaded with 50:50 PLG, 75:25 PLG and PLA/PEG-blended microparticles was evaluated in adult mice by oral immunization. Significantly higher antibody responses and serum immunoglobin Ig G, IgA and IgM responses were obtained when sera from both VC-loaded 75:25 PLG and PLA/PEG-blended microparticles immunized mice were titrated against VC. The most immunogenicity in evoking serum IgG, IgA and IgM responses was immunized by VC-loaded PLA/PEG-blended microparticles, and with VC challenge in mice, the survival rate (91.7%).     

The characteristics of betamethasone-loaded chitosan microparticles by spray-drying method

Betamethasone (BTM)-loaded microparticles prepared by a spray drying method using chitosan (CTS) as raw material, type-A gelatin and ethylene oxide-propylene oxide block copolymer (Pluronic F68) as modifiers. The BTM-loaded in varied chitosan/Pluronic F68/gelatin microparticle formulations was investigated. By properly choosing excipient type and concentration a high degree of control was achieved over the physical properties of the BTM-loaded microparticles. Microparticle characteristics (zeta potential, tap density, particle size and yield), loading efficiencies, microparticle morphology and in-vitro release properties were examined. Surface morphological characteristics and surface charges of prepared microparticles were observed by using scanning electron microscopy (SEM) and microelectrophoresis. A SEM micrograph shows that the particle sizes of the varied chitosan composed microparticles ranged from 1.1-4.7 microm and the external surfaces appear smooth. The BTM-loaded microparticles entrapped in the chitosan/Pluronic F68/gelatin microparticles with trapping efficiencies up to 93%, collected yield rate 44%, and mean particle size varied between 1-3 microm, positive surface charge (20-40 mv), and tap densities (0.04-0.40 g/cm3) were obtained. The collected BTM yield and size of particle was increased with increasing BTM-loaded amount but both zeta potential and tap density of the particles decreased with increasing BTM-loaded amount. The in vitro release of BTM showed a dose-dependent burst followed by a slower release phase that was proportional to the drug concentration in the concentration range between 5-30%w/w. The in vitro drug release from the chitosan/Pluronic F68/gelatin 1/0.1/0.4 microspheres had a prolong release pattern. These formulation factors were correlated to particulate characteristics for optimizing BTM microspheres in pulmonary delivery.     

5-Fluorouracil encapsulated alginate beads for the treatment of breast cancer

Alginate beads containing 5-fluorouracil (5-FU) were prepared by the gelation of alginate with calcium cations. Alginate beads loaded with 5-FU were prepared at 1.0 and 2.0% (w/v) polymers. The effect of polymer concentration and the drug loading (1.0, 5.0 and 10%) on the release profile of 5-FU was investigated. As the drug load increased, larger beads were obtained in which the resultant beads contained higher 5-FU content. The encapsulation efficiencies obtained for 5-FU loads of 1.0, 5.0 and 10% (w/v) were 3.5, 7.4 and 10%, respectively. Scanning electron microscopy (SEM) and particle size analysis revealed differences between the formulations as to their appearance and size distribution. The amount of 5-FU released from the alginate beads increased with decreasing alginate concentrations.     

Layer-by-layer assembly of poly(l-glutamic acid)/chitosan microcapsules for high loading and sustained release of 5-fluorouracil

Hollow polyelectrolyte microcapsules based on poly(l-glutamic acid) (PLGA) and chitosan (CS) with opposite charges were fabricated by layer-by-layer (LbL) assembly technique using melamine formaldehyde (MF) microparticles as sacrificial templates. The LbL assembly of polyelectrolytes and the resultant PLGA/CS microcapsules were characterized. A hydrophilic anticancer drug, 5-fluorouracil (5-FU), was chosen to investigate the loading and release properties of the microcapsules. The PLGA/CS microcapsules show high loading capacity of 5-FU under conditions of high drug concentration and salt adding. The high loading can be ascribed to spontaneous deposition of 5-FU induced by hydrogen bonding between 5-FU and PLGA/CS microcapsules. The PLGA/CS microcapsules show sustained release behavior. The release rate of 5-FU drastically slows down after loading in PLGA/CS microcapsules. The 5-FU release from PLGA/CS microcapsules can be best described using Ritger-Peppas or Baker-Londale models, indicating the diffusion mechanism of 5-FU release from the PLGA/CS microcapsules. In vitro cytotoxicity evaluation by the MTT assay shows good cell viability over the entire concentration range of PLGA/CS microcapsules. Therefore, the novel PLGA/CS microcapsules are expected to find application in drug delivery systems because of the properties of biodegradability, high loading, sustained release and cell compatibility.     

Controlled release study of 5-fluorouracil-loaded chitosan/polyethylene glycol microparticles

The aim of this research is to reduce the frequency of taking therapeutic drugs. Thus, anti-cancer drug [5-fluorourical (5-FU)] loaded chitosan/polyethylene glycol microparticles were prepared by a phase-inversion technique with tripolyphosphate (TPP) used as a cross-linking agent. The relationships between 5-FU release behavior/encapsulation efficiencies and chitosan concentrations, TPP concentrations, as well as cross-linking time were studied to identify better/superior conditions (3.5 wt% chitosan, 3 wt% TPP, and cross-linking time?=?4?h) for preparing 5-FU-loaded microparticles. Furthermore, in order to ascertain the influence of their physical properties on 5-FU release performance, 5-FU-loaded microparticles were evaluated by swelling tests and scanning electron microscopy.     

The mechanism of PLA microparticle formation by waterin-oil-in-water solvent evaporation method

Microparticles containing ovalbumin as a model protein drug were prepared using poly(L-lactide; PLA) with a water-in-oil-in-water emulsion/solvent evaporation technique. The dispersed phase was PLA dissolved in dichloromethane (DCM), and the continuous phase was water-containing polyvinyl pyrolidone (PVP) as stabilizer with sodium chloride. Microparticle characteristics, loading efficiencies, protein distribution in microparticles, and in-vitro release properties were investigated. The OVA leaking into the continuous phase during the formation of microparticle by DCM evaporation was also evaluated. Results show that OVA was successfully entrapped in the microparticles with trapping efficiencies up to 72%, loading level 8.7% w/v, and particle size 14 #181;m. The semi-solid suspension changes to a solid particle happened during a 10-min period. Total protein-leaking amount was reduced after addition of NaCl in the continuous aqueous phase, which resulted from reducing the solidification time and protein-leaking rate. Using 5% w/v NaCl in the continuous phase resulted in higher loading content (87.2 1.0 #181;g/mg), and loading efficiency (72.2%), which resulted from more protein in the deeper layer (50.2 2.3 #181;g/mg) and higher microparticle yield (75.2%) than without NaCl (loading content: 74.0 1.0 #181;g/mg; loading efficiency 51.8%; deeper layer content: 18.3 3.5 #181;g/mg; yield: 63.6%). These results constitute a step forward in the improvement of existing technology in controlling protein encapsulation and delivery from microparticles prepared by the multiple emulsion solvent evaporation method.     

Fabrication,characterization and in vitro evaluation of poly(D,L-lactide-co-glycolide) microparticles loaded with polyamidoamine–plasmid DNA dendriplexes for applications in nonviral gene delivery

We report, for the first time, on the preparation, characterization and in vitro testing of poly(D,L-lactide-co-glycolide) (PLGA) microparticles loaded with polyamidoamine (PAMAM)–plasmid DNA (pDNA) dendriplexes. Loading of pDNA into the PLGA microparticles increased by 150% when pDNA was first complexed with PAMAM dendrimers relative to loading of pDNA alone. Scanning electron microscopy (SEM) showed that the presence of PAMAM dendrimers in the PLGA microparticles created porous features and indentations on the surface of the microparticles. Loading PLGA microparticles with PAMAM–pDNA dendriplexes lowered the average PLGA microparticle size and changed the surface charge of the microparticles from negative to positive when compared to PLGA microparticles loaded with pDNA alone. The zetapotential and buffering capacity of the microparticles increased as the generation of the PAMAM dendrimer loaded in the PLGA microparticles increased. Gel electrophoresis assays showed that all the PLGA microparticle formulations were able to entrap the pDNA within the PLGA matrix. There was no significant difference in the cytotoxicity of PLGA microparticles loaded with PAMAM–pDNA dendriplexes when compared to PLGA microparticles loaded with pDNA alone. Furthermore, and in contrast to PAMAM dendrimers alone, the generation of the PAMAM dendrimer loaded in the PLGA microparticles had no significant impact on cytotoxicity or transfection efficiencies in human embryonic kidney (HEK293) or Monkey African green kidney fibroblast-like (COS7) cells. The transfection efficiency of PLGA microparticles loaded with generation 3 (G3) PAMAM–pDNA dendriplexes was significantly higher than PLGA microparticles loaded with pDNA alone in HEK293 and COS7 cells. PLGA microparticles loaded with G3 PAMAM–pDNA dendriplexes generated equivalent transfection efficiencies as (G3 to G6) PAMAM–pDNA dendriplexes alone in COS7 cells when the transfection was carried out in serum containing media. The delivery system developed in this report has low toxicity, high pDNA loading efficiencies and high transfection efficiencies that are not reduced in the presence of serum. A delivery system with these characteristics is expected to have significant potential for translational applications. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:368–384, 2010     

Monitoring Microviscosity and Microacidity of the Albumin Microenvironment Inside Degrading Microparticles from Poly(lactide-co-glycolide) (PLG) or ABA-triblock Polymers Containing Hydrophobic Poly(lactide-co-glycolide) A Blocks and Hydrophilic Poly(ethyleneoxide) B Blocks

Purpose. The purpose of this study was to monitor the microenvironment of an encapsulated model protein during the release from biodegradable microparticles (MP) made from three different polymers, namely poly(lactide-co-glycolide) (PLG) and ABA-triblock polymers containing hydrophobic poly(lactide-co-glycolide) A blocks and hydrophilic poly(ethyleneoxide) B blocks with an A:B ratio of 90:10 (ABA10) and 70:30 (ABA30). Methods. MP loaded with spin labeled albumin were prepared by a w/o/w technique. The particles were characterized by light scattering and electron microscopy. In vitro release of albumin was determined by size exclusion chromatography. Light microscopic experiments were conducted to visualize water penetration in the matrix. The protein microenvironment inside the degrading microparticles was characterized noninvasively by 2 GHz EPR spectroscopy. Results. Water penetrated rapidly into all MP in the range of few minutes. A burst release was observed for PLG. The release from ABA block-polymers continued for over 14 days despite the rapid solubilization of the protein inside the microparticles. The initial microviscosity of the protein environment inside the ABA particles after exposure to buffer was 2 mm²/s and increased with time. A gradual decrease of the pH to a value of 3.5 was observed within the MP. Conclusions. The data indicate that the microviscosity and microacidity inside protein loaded microparticles can be studied nondestructively by EPR spectroscopy. Our results clearly demonstrate that ABA-block polymers are superior to PLG allowing a controlled release of proteins from swollen microspheres.     

Sustained release of isoniazid from a single injectable dose of poly (DL-lactide-co-glycolide) microparticles as a therapeutic approach towards tuberculosis

Drug delivery strategies to achieve a sustained drug release and increased bioavailability involve the use of biodegradable polymeric drug carriers. Poly (DL-lactide-co-glycolide) (PLG) microparticles were investigated as carriers for isoniazid (INH). In vitro and in vivo release of INH from different formulations of PLG microparticles was examined. In vitro experiments showed a sustained release of INH up to 6 days from non-porous microparticles while porous microparticles released INH over 3 days. Both porous and non-porous microparticles released INH in plasma for up to 2 days. Hardened PLG microparticles sustained release of INH for up to 7 weeks both in vitro and in vivo. The concentrations of INH obtained at all times were much higher than the minimum inhibitory concentration (MIC) of INH. Controls injected with free INH showed release of INH in plasma for up to 12 h and in organs for up to 24 h. There was no hepatotoxicity induced as compared with control animals. Taken together these results suggest that PLG-based antitubercular drugs may serve as ideal therapeutic agents for the treatment of tuberculous infections.     

The mechanism of PLA microparticle formation by water-in-oil-in-water solvent evaporation method

Microparticles containing ovalbumin as a model protein drug were prepared using poly(L-lactide; PLA) with a water-in-oil-in-water emulsion/solvent evaporation technique. The dispersed phase was PLA dissolved in dichloromethane (DCM), and the continuous phase was water-containing polyvinyl pyrolidone (PVP) as stabilizer with sodium chloride. Microparticle characteristics, loading efficiencies, protein distribution in microparticles, and in-vitro release properties were investigated. The OVA leaking into the continuous phase during the formation of microparticle by DCM evaporation was also evaluated. Results show that OVA was successfully entrapped in the microparticles with trapping efficiencies up to 72%, loading level 8.7% w/v, and particle size 14 microm. The semi-solid suspension changes to a solid particle happened during a 10-min period. Total protein-leaking amount was reduced after addition of NaCl in the continuous aqueous phase, which resulted from reducing the solidification time and protein-leaking rate. Using 5% w/v NaCl in the continuous phase resulted in higher loading content (87.2 +/- 1.0 microg/mg), and loading efficiency (72.2%), which resulted from more protein in the deeper layer (50.2 +/- 2.3 microg/mg) and higher microparticle yield (75.2%) than without NaCl (loading content: 74.0 +/- 1.0 microg/mg; loading efficiency 51.8%; deeper layer content: 18.3 +/- 3.5 microg/mg; yield: 63.6%). These results constitute a step forward in the improvement of existing technology in controlling protein encapsulation and delivery from microparticles prepared by the multiple emulsion solvent evaporation method.     

Optimizing formulation factors in preparing chitosan microparticles by spray-drying method

The chitosan only, chitosan/Pluronic F68, chitosan/gelatin, chitosan/Pluronic F68/gelatin microparticles and betamethasone-loaded chitosan/Pluronic F68/gelatin microparticles were successfully prepared by a spray-drying method. Microparticle characteristics (yield rate, zeta potential, particle size and tap density), loading efficiencies, microparticle morphology and in-vitro release properties were investigated. By properly choosing excipient type, concentration and varying the spray-drying parameters, a high degree of control was achieved over the physical properties of the dry chitosan powders. SEM micrograph shows that the particle sizes of the varied chitosan composed microparticles ranged from 2.12-5.67 microm and the external surfaces appear smooth. Using betamethasone as model drug, the spray-drying is a promising way to produce good spherical and smooth surface microparticles with a narrow particle size range for controlled delivery of betamethasone. The positively charged betamethasone-loaded microparticles entrapped in the chitosan/Pluronic F68/gelatin microparticles with trapping efficiencies up to 94.5%, yield rate 42.5% and mean particle size 5.64 microm varied between 4.32-6.20 microm and tap densities 0.128 g/cm(3). The pH of particle was increased with increasing betamethasone-loaded amount, but both zeta potential and tap density of the particles decreased with increasing betamethasone-loaded amount. The betamethasone release rates from chitosan/Pluronic F68/gelatin microparticles were influenced by the drug/polymer ratio in the manner that an increase in the release% and burst release% was observed when the drug loading was decreased. The in vitro release of betamethasone showed a dose-dependent burst followed by a slower release phase that was proportional to the drug concentration in the concentration range between 14-44%w/w.     

Floating microparticles based on low density foam powder

The aim of this study was to develop a novel multiparticulate gastroretentive drug delivery system and to demonstrate its performance in vitro. Floating microparticles consisting of (i) polypropylene foam powder; (ii) verapamil HCl as model drug; and (iii) Eudragit RS, ethylcellulose (EC) or polymethyl methacrylate (PMMA) as polymers were prepared with an O/W solvent evaporation method. The effect of various formulation and processing parameters on the internal and external particle morphology, drug loading, in vitro floating behavior, in vitro drug release kinetics, particle size distribution and physical state of the incorporated drug was studied. The microparticles were irregular in shape and highly porous. The drug encapsulation efficiency was high and almost independent of the theoretical loading. Encapsulation efficiencies close to 100% could be achieved by varying either the ratio 'amount of ingredients: volume of the organic phase' or the relative amount of polymer. In all cases, good in vitro floating behavior was observed. The release rate increased with increasing drug loading and with decreasing polymer amounts. The type of polymer significantly affected the drug release rate, which increased in the following rank order: PMMA相似文献   

Improving Protein Delivery from Microparticles Using Blends of Poly(DL lactide co-glycolide) and Poly(ethylene oxide)-poly(propylene oxide) Copolymers

Purpose. Microparticles containing ovalbumin as a model for protein drugs were formulated from blends of poly(DL lactide-co-glycolide) and poly(ethylene oxide)-poly(propylene oxide) copolymers (Pluronic). The objectives were to achieve uniform release characteristics and improved protein delivery capacity. Methods. The water- in oil -in oil emulsion/solvent extraction technique was used for microparticle production. Results. A protein loading level of over 40% (w/w) was attained in microparticles having a mean diameter of approximately 5 µm. Linear protein release profiles over 25 days in vitro were exhibited by certain blend formulations incorporating hydrophilic Pluronic F127. The release profile tended to plateau after 10 days when the more hydrophobic Pluronic L121 copolymer was used to prepare microparticles. A delivery capacity of 3 µg OVA/mg particles/ day was achieved by formulation of microparticles using a 1:2 blend of PLG:Pluronic F127. Conclusions. The w/o/o formulation approach in combination with PLG:Pluronic blends shows potential for improving the delivery of therapeutic proteins and peptides from microparticulate systems. Novel vaccine formulations are also feasible by incorporation of Pluronic L121 in the microparticles as a co-adjuvant.