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PubMed2003

Double walled POE/PLGA microspheres: encapsulation of water-soluble and water-insoluble proteins and their release properties.

The poly(orthoester) (POE)-poly(D,L-lactide-co-glycolide) (50:50) (PLGA) double-walled microspheres with 50% POE in weight were loaded with hydrophilic bovine serum albumin (BSA) and hydrophobic cyclosporin A (CyA). Most of the BSA and CyA was entrapped within the shell and core, respectively, because of the difference in their hydrophilicity. The morphologies and release mechanisms of proteins-loaded double-walled POE/PLGA microspheres were investigated. Scanning electron microscope studies revealed that the CyA-BSA-loaded double-walled POE/PLGA microspheres yielded a more porous surface and PLGA shell than those without BSA. The neat POE and PLGA yielded slow and incomplete CyA and BSA release. In contrast, nearly complete BSA and more than 95% CyA were released in a sustained manner from the double-walled POE/PLGA microspheres. Both the BSA- and CyA-BSA-loaded POE/PLGA microspheres yielded a sustained BSA release over 5 days. The CyA release pattern of the CyA-loaded double-walled POE/PLGA microspheres was biphasic, characterized by a slow release over 15 days followed by a sustained release over 27 days. However, the CyA-BSA-loaded double-walled POE/PLGA microspheres provided a more constant and faster CyA release due to their more porous shell. In the CyA-BSA-loaded double-walled POE/PLGA microspheres system, the PLGA layer acted as a carrier for BSA and mild reservoir for CyA. During the first 5 days, most BSA was released from the shell but only 14% CyA was left from the microspheres. Subsequently, more than 80% CyA were released in the next 25 days. The distinct structure of double-walled POE/PLGA microspheres would make an interesting device for controlled delivery of therapeutic agents.

Animals↗

PubMed1996

Size effect on the antibody production induced by biodegradable microspheres containing antigen.

Poly(L-lactic acid) (PLLA) microspheres containing a model antigen, ovalbumin (OVA), were prepared by the evaporation method using double emulsion, and fractionated into different sizes by counterflow elutriation. Following the intraperitoneal (i.p.) and subcutaneous (s.c.) injection of the microspheres to mice, the titer of anti-OVA antibody in the serum was measured to assess the size effect on the profile of antibody production. OVA was released from the microspheres for 80 days, irrespective of the microsphere size. In both the s.c. and i.p. immunization, the serum level of anti-OVA IgG antibody in the mice induced by the microspheres containing OVA was higher than that of free OVA when compared at the same dose. The serum level of antibody in the mice i.p. injected with the microspheres tended to increase with the decreasing size. On the other hand, in the s.c. immunization, the microsphere size had little influence on the antibody production. It is possible that the injected microspheres tend to aggregate in the s.c. tissue, disappearing the size effect on the antibody production. Since the amount of microspheres injected increases with the decreasing size when their OVA loading is fixed, the increase in the amount will promote the interaction with immune cells, resulting in an enhanced antibody production. The cell interaction with the microspheres in the peritoneal cavity seems to be influenced by their size to a greater extent than in the s.c. tissue, probably because of their more frequent interaction with immune cells.

Animals↗

PubMed2001

The study of drug release from microspheres adhered on pig vesical mucosa.

The object of our work is the preparation of a mucoadhesive drug delivery system intended for intravesical application. In the present work, microspheres with Eudragit RS matrix polymer and different mucoadhesive polymers, i.e. chitosan hydrochloride (Ch), sodium salt of carboxymethyl cellulose (CMC) and polycarbophil (PC) were prepared to evaluate their influence on the mucoadhesive properties of microspheres. Different parameters were determined and their influence on pipemidic acid release from microspheres adhered on intact and damaged pig vesical mucosa was evaluated: swelling of polymers, mucoadhesion strength of polymeric films and drug dissolution according to USP XXIV method. The dissolution rate from microspheres containing different mucoadhesive polymers decreases as follows: PC>Ch>CMC. PC swelled to the largest volume among all polymers and as a result the fastest release of the drug from PC microspheres was obtained. The release rate of pipemidic acid from microspheres adhered on intact mucosa followed the order PC>CMC>Ch. These results show that both drug dissolution and mucoadhesion strength strongly influence drug release from adhered microspheres. The slowest release from Ch microspheres could be interpreted by the largest mucoadhesion strength of Ch polymeric films. The release rate of pipemidic acid from microspheres adhered on damaged mucosa followed the order PC=Ch>CMC. The results obtained on pathologically changed mucosa model support the indication of the role of glycosaminoglycans and polymer charge in the mucoadhesion process on vesical mucosa. Analysis of release data shows that the drug dissolution profiles follow the Higuchi kinetics better than the release profiles from adhered microspheres and different kinetics might be a consequence of different release mechanisms.

Acrylic Resins↗

PubMed2003

High-density, microsphere-based fiber optic DNA microarrays.

A high-density fiber optic DNA microarray has been developed consisting of oligonucleotide-functionalized, 3.1-microm-diameter microspheres randomly distributed on the etched face of an imaging fiber bundle. The fiber bundles are comprised of 6000-50000 fused optical fibers and each fiber terminates with an etched well. The microwell array is capable of housing complementary-sized microspheres, each containing thousands of copies of a unique oligonucleotide probe sequence. The array fabrication process results in random microsphere placement. Determining the position of microspheres in the random array requires an optical encoding scheme. This array platform provides many advantages over other array formats. The microsphere-stock suspension concentration added to the etched fiber can be controlled to provide inherent sensor redundancy. Examining identical microspheres has a beneficial effect on the signal-to-noise ratio. As other sequences of interest are discovered, new microsphere sensing elements can be added to existing microsphere pools and new arrays can be fabricated incorporating the new sequences without altering the existing detection capabilities. These microarrays contain the smallest feature sizes (3 microm) of any DNA array, allowing interrogation of extremely small sample volumes. Reducing the feature size results in higher local target molecule concentrations, creating rapid and highly sensitive assays. The microsphere array platform is also flexible in its applications; research has included DNA-protein interaction profiles, microbial strain differentiation, and non-labeled target interrogation with molecular beacons. Fiber optic microsphere-based DNA microarrays have a simple fabrication protocol enabling their expansion into other applications, such as single cell-based assays.

Equipment Design↗

PubMedDate not supplied

Preparation and characterization of temperature-sensitive poly(N-isopropylacrylamide)-b-poly(D,L-lactide) microspheres for protein delivery.

Temperature-sensitive diblock copolymers, poly(N-isopropylacrylamide)-b-poly(D,L-lactide) (PNIPAAm-b-PLA) with different PNIPAAm contents were synthesized and utilized to fabricate microspheres containing bovine serum albumin (BSA, as a model protein) by a water-in-oil-in-water double emulsion solvent evaporation process. XPS analysis showed that PNIPAAm was a dominant component of the microspheres surface. BSA was well entrapped within the microspheres, and more than 90% encapsulation efficiency was achieved. The in vitro degradation behavior of microspheres was investigated using SEM, NMR, FTIR, and GPC. It was found that the microspheres were erodible, and polymer degradation occurred in the PLA block. Degradation of PLA was completed after 5 months incubation in PBS (pH 7.4) at 37 degrees C. A PVA concentration of 0.2% (w/v) in the internal aqueous phase yielded the microspheres with an interconnected porous structure, resulting in fast matrix erosion and sustained BSA release. However, 0.05% PVA produced the microspheres with a multivesicular internal structure wrapped with a dense skin layer, resulting in lower erosion rate and a biphasic release pattern of BSA that was characterized with an initial burst followed by a nonrelease phase. The microspheres made from PNIPAAm-b-PLA with a higher portion of PNIPAAm provided faster BSA release. In addition, BSA release from the microspheres responded to the external temperature changes. BSA release was slower at 37 degrees C (above the LCST) than at a temperature below the LCST. The microspheres fabricated with PNIPAAm-b-PLA having a 1:5 molar ratio of PNIPAAm to PLA and 0.2% (w/v) PVA in the internal aqueous phase provided a sustained release of BSA over 3 weeks in PBS (pH 7.4) at 37 degrees C.

Absorption↗

PubMed1999

Use of infrared spectroscopy to assess secondary structure of human growth hormone within biodegradable microspheres.

The purpose of this study was to test the utility of infrared (IR) spectroscopy to determine protein secondary structure in biodegradable microspheres. Encapsulation of proteins within biodegradable polymers, [e.g. poly(lactic-co-glycolic acid) (PLGA)] for controlled drug release has recently been the subject of intense research effort. The ability to assess protein integrity after microsphere production is necessary to successfully produce microspheres that release native proteins. We used IR spectroscopy, a noninvasive method-as opposed to conventional organic solvent extraction or in vitro release at elevated temperature-to assess the secondary structure of recombinant human growth hormone (rhGH) within dry and rehydrated microspheres. PLGA microspheres containing rhGH with different excipients were prepared by a conventional double-emulsion method. The protein IR spectra indicated that the encapsulation process could perturb the structure of rhGH and that excipients could inhibit this damage to varying degrees. A strong positive correlation was found between intensity of the dominant alpha-helical band in the spectra of rhGH in rehydrated microspheres and the percent monomer released from microspheres during incubation in buffer. We also studied microspheres prepared with zinc-precipitated rhGH. The addition of Zn2+ during microsphere processing partially inhibited protein unfolding and fostered complete refolding of rhGH upon rehydration. In conclusion, IR spectroscopy can serve as a valuable tool to assess protein structure within both dried and rehydrated microspheres.

Delayed-Action Preparations↗

PubMed1992

Adsorption of fluorescein dyes on albumin microspheres.

The surface characteristics of bovine and egg albumin microspheres were examined using four anionic dyes; sodium fluorescein, eosin, erythrosin, rose bengal, and the cationic dye rhodamine B. The adsorption isotherms of the dyes on unloaded albumin microspheres exhibited Langmuir behavior for dilute solutions of rose bengal, erythrosin, and eosin, suggesting monolayer formation in the initial stages of the sorption process. The adsorption capacity of the microspheres for the dyes (k2) and the affinity constants of the dyes for the microspheres (k1) were found to depend on both the polarizability and the hydrophobic properties of the dye, presumably reflecting the heterogeneous character of the microsphere surface. Further, the extent of sorption at higher dye concentrations was found to depend on the ability of the dye to form stable aggregates inside the microspheres and on environmental long-range forces acting at these sites. At both low and high dye concentrations, the amount adsorbed to the microsphere surface increased with increasing hydrophobicity of the dyes. The lowest adsorption was observed for the nonsubstituted dye fluorescein, whereas the most hydrophobic dye used, rose bengal, was completely adsorbed onto the microsphere surface. The data suggest that the bovine albumin microsphere surfaces are highly hydrophobic and less porous than egg albumin microsphere surfaces.

Adsorption↗

PubMed1993

Effect of splenic congestion associated with haemolytic anaemia on filtration of 'spleen-homing' microspheres.

1. The surface of large model 125I-labelled polystyrene microspheres (220 nm in diameter) was coated with the polyoxyethylene/polyoxypropylene block co-polymer poloxamine-908. The coated microspheres were injected intravenously into rats. Up to 40% of the administered dose had accumulated in the spleen by a filtration mechanism, as compared with 5% for uncoated microspheres, at 3 h after administration. The enhanced splenic sequestration of microspheres was accompanied by a decrease in the liver uptake. In contrast, smaller poloxamine-908-coated microspheres (60 nm in diameter) effectively avoided uptake by both the liver and the spleen and remained in systemic circulation. 2. The effect of splenic congestion, associated with phenylhydrazine-induced haemolytic anaemia, on filtration of poloxamine-908-coated microspheres was studied. The enlarged spleen of the anaemic rats was incapable of efficiently filtering large poloxamine-908-coated microspheres when compared with the spleen of normal animals. This was suggested to be the result of extensive 'clogging' of the red pulp by damaged erythrocytes. However, the splenic filtration of large coated microspheres was still five-fold higher than that of uncoated microspheres of similar size in anaemic animals. 3. The potential use of large sterically stabilized colloids and drug carriers for selective spleen scanning and splenic drug delivery in pathological conditions, where anaemia prevails, is discussed. 4. Sterically stabilized microspheres may have potential for re-examining the microcirculatory pathways in healthy spleen and various splenomegalies.

Anemia, Hemolytic↗

PubMedDate not supplied

Release characteristics of pectin microspheres prepared by an emulsification technique.

The potential application of pectin as a matrix polymer for making microspheres by an emulsification technique was explored, and the drug release property of these pectinate microspheres containing drug cores of varying aqueous solubilities: sulphanilamide, sulphaguanidine and sulphathiazole, was investigated using different dissolution media. The size and size distribution, specific surface area, drug content and drug release property of the pectinate microspheres were determined. The solubility and solution pH of drugs and their propensity to interact with pectin were characterized. Pectinate microspheres were successfully prepared by external gelation, using a modified emulsification technique. The kinetics of drug release from the microspheres best fitted Higuchi's model. Interestingly, the lowest percentage of drug released was produced by microspheres which were smallest in size and, therefore, largest in specific surface area, and containing sulphanilamide, the most aqueous soluble and the lowest molecular weight drug. Mathematical correlation study indicated that the drug release profile of pectinate microspheres was notably affected by the drug content and the extent of drug-pectin interaction in the microspheres. Generally, a higher percentage of drug was released from the microspheres with a higher drug content and/or lower extent of drug-pectin interaction. The extent of drug-pectin interaction was highest in microspheres containing sulphanilamide, followed by sulphaguanidine and sulphathiazole, opposite to that of drug content.

Delayed-Action Preparations↗

PubMedDate not supplied

Oxprenolol-loaded bioadhesive microspheres: preparation and in vitro/in vivo characterization.

Biologically adhesive delivery systems offer important advantages over conventional drug-delivery systems. In this paper, microspheres intended as a sustained release carrier for oral or nasal administration have been prepared by associating a known bioadhesive polymer, poly(acrylic acid), in gelatin microspheres. A model drug oxprenolol hydrochloride was chosen. It was found that some of the formulation variables can influence the characteristics of the beads in a controlled manner. The internal structure of the microspheres studied by X-ray diffraction, thermal analysis and optical microscopy showed the absence of drug crystals in microspheres and a lowering in the glass transition temperature. The dynamic swelling of the beads obeyed the square root of time and a shift from the diffusional to the relaxational process dependent on the content of poly(acrylic acid) in gelatin microspheres was observed. As expected, drug release from gelatin/poly(acrylic acid) microspheres was influenced by the poly(acrylic acid) content in beads, by the particle size of microspheres and by the pH of the medium. The mechanism of release was analysed by applying the empirical exponential equation and by calculation of the approximate contribution of the diffusional and relaxational mechanisms to the anomalous release process by fitting the data to the coupled Fickian/Case II equation. In vitro and in vivo experiments in rats showed good adhesive characteristics of the gelatin/poly(acrylic acid) microspheres, which were greater if the poly(acrylic acid) content was greater. A significant retardation in gastric and intestinal emptying time of the beads was observed. This was also suggested by the bioavailability of the model drug after intragastric and intranasal administration of the microspheres. The pharmacokinetic parameters after microsphere administration were more appropriate to a slow release drug-delivery system. The work suggests the potential of this pharmaceutical delivery system as an alternative controlled-release dosage form, either for oral or nasal administration.

Acrylates↗

PubMedDate not supplied

Poly (D,L-lactide-co-glycolide) microspheres for long-term intravitreal delivery of aciclovir: influence of fatty and non-fatty additives.

Aciclovir (acicloguanosine) has been demonstrated to be effective in the treatment of intraocular pathologies such as herpes simplex virus retinitis and acute retinal necrosis. Although intravitreal injections have been used with fewer side-effects than intravenous administration, the risk of complications increases with the frequency of intravitreous injections. For this reason, a biodegradable drug-delivery system, such as microspheres, able to promote prolonged release of the drug, offers a good alternative to multiple intraocular administrations. In this work, aciclovir-containing poly (D,L-lactide-co-glycolide) microspheres were prepared by the solvent evaporation method. Seven additives were incorporated in the microspheres to modulate the in vitro release rate of the drug: four non-fatty substances (polyethylene glycol 300, polyethylene glycol 1500, hydroxypropyl methylcellulose and gelatin) and three fatty substances (isopropyl myristate, vitamin E and Labrafil M 1944 CS). Morphology of microspheres was evaluated by scanning electron microscopy. Granulometric analysis showed that particle size distribution was significantly influenced by the incorporation of additives. Loading efficiency decreased when fatty substances were added, whereas non-fatty additives promoted higher incorporation of the drug. Infrared and differential scanning calorimetry analyses indicated that microspheres prepared by the solvent evaporation process were not influenced by the type of additive used. In all cases, the initial burst resulted less than 5%. Additive-free microspheres showed a slow release within the first days, but when additives were incorporated, in general, the release rates of the drug were increased. Best release results were obtained for gelatin-containing microspheres. The release of aciclovir from these microspheres was adjusted to a zero-order kinetic from 1 to 49 days with a release constant of 1.13 microg/day/mg microspheres. A dose of 0.74 mg microspheres would be therapeutic for the herpes simplex and Epstein-Barr viruses (MIC 0.1 microg/ml) and 7.4 mg for varicella zoster virus (MIC 1 microg/ml) treatment in an animal model.

Acyclovir↗

PubMed2004

Evaluation of enteric matrix microspheres prepared by emulsion-solvent evaporation using scanning electron microscopy.

Theophylline microspheres were prepared by the emulsion-solvent evaporation method using cellulose acetate butyrate (CAB381-20) and mixtures of CAB381-20(R) and cellulose acetate phthalate. The physical state of the drug, polymers and microspheres surfaces were determined using scanning electron microscopy. For those microspheres prepared using mixtures of CAB381-20 and cellulose acetate phthalate, scanning electron micrographs were taken before dissolution and also at different stages of dissolution (in SGF, pH 1.2 and in simulated intestinal fluid, pH 7.5). Micrographs were taken of the outside surfaces of the microspheres and of the cleaved microspheres showing their interiors (core). Drug crystals were observed on or near the surface of microspheres prepared from the polymer mixtures, while no drug particles or crystals were seen on the surfaces of microspheres prepared solely from CAB381-20. An acid wash for less than 2 min was capable of extracting all drug on the surface of the microspheres prepared from a mixture of CAB381-20 and cellulose acetate phthalate. The absence of drug crystals on the surface of CAB381-20 microspheres is believed to prevent initial drug release and create a lag time in release profiles. Results suggest that in both microsphere formulations, a layer of drug-free polymer is formed outside the core matrix and is believed to be responsible for the near zero-order release profiles.

Cellulose↗

PubMed2005

Determination of microsphere solidification time in the solvent evaporation process.

The aim of this work was to define the time of microsphere solidification during the solvent evaporation process. Microspheres were prepared by the solvent evaporation method, using acetone/liquid paraffin solvent system, ketoprofen as a model drug and Eudragit RS as a matrix polymer. Two sets of experiments were performed--in the first one the initial temperature of the emulsion system was 5 degrees C and in the second one 25 degrees C. In each set, two batches of microspheres were compared at constant emulsion stirring rate 250 and 1000 rpm and intermediate batches where the emulsion stirring rate was lowered from 1000 to 250 rpm at pre-defined times after the beginning of the inner phase solvent evaporation. By comparison of the properties of these microspheres, an insight was obtained into the mechanism of microspheres formation. The criterion for determination of microsphere solidification time was the resemblance between the microsphere properties of the batches prepared by stirring rate change and the batch prepared by constant stirring at 1000 rpm. A stirring rate change after the solidification has no influence on microsphere properties, that means that they are the same as of the batch prepared by constant stirring at 1000 rpm. The results of the sieve analysis and particle size distribution of microspheres show that the time of microspheres solidification is in the interval between 15-20 min if the initial temperature is 5 degrees C and between 10-20 min if the initial temperature is 25 degrees C. From the release profiles of ketoprofen, one can infer that the times of solidification for both initial temperatures are a bit lower. The microscopic pictures, which enable one to follow the processes in the system, confirmed the result obtained by the sieve analysis. In spite of its inability to distinguish between single particles and agglomerates, the sieve analysis enabled one to determine the actual time of solidification, while the drug release determination was not sensitive enough to trace small differences in surface area due to particles aggregation.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2006

Effect of manufacturing parameters on the characteristics of vitamin C encapsulated tripolyphosphate-chitosan microspheres prepared by spray-drying.

To prepare the sustained release vitamin C carriers, vitamin C was successfully encapsulated in tripolyphosphate (TPP) cross-linked chitosan (TPP-chitosan) microspheres by the spray-drying method at different manufacturing conditions. Manufacturing parameters (inlet temperature, liquid flow rate, chitosan concentration and volume of 1% w/v TPP solution) had a significant influence on the characteristics of thus prepared microspheres. The optimum spray-drying conditions such as inlet temperature, liquid flow rate and compressed air flow rate for the encapsulation of vitamin C in TPP-chitosan microspheres was found to be 170 degrees C, 2 ml min(-1) and 101 min(-1), respectively. The size and yield of the TPP-chitosan microspheres ranged from 3.9-7.3 microm and 54.5-67.5%, respectively. The encapsulation efficiency of TPP-chitosan microspheres ranged from 45.72-68.7% and it decreased with the increasing volume of 1% w/v TPP solution. At the same cross-linking extent, the encapsulation efficiency of TPP-chitosan microspheres increased when the concentration of chitosan was increased from 0.5-1% w/v. Effect of volume of 1% w/v TPP solution on the surface morphology of chitosan microspheres was examined by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). These studies revealed that chitosan solution (250 ml) cross-linked with 15 ml 1% w/v TPP solution produced more porous microspheres than that cross-linked with 5 and 10 ml TPP solution. The release rate of vitamin C from TPP-chitosan microspheres decreased when the concentration of chitosan was increased from 0.5-1.0% w/v. Vitamin C release rate was also modulated by varying the volume of 1% w/v TPP solution. The release rate of vitamin C from TPP-chitosan microspheres decreased with increasing volume (5-15 ml) of 1% w/v TPP solution.

Ascorbic Acid↗

PubMed2006

Fucosphere--new microsphere carriers for peptide and protein delivery: preparation and in vitro characterization.

PURPOSE: Fucoidan is a complex polysaccharide containing sugars and high amounts of sulphate derived from marine brown algaes. In this study, a new microsphere-delivery system based on cross-linking of fucoidan with chitosan, named Fucosphere, was evaluated as a drug carrier. Bovine serum albumin (BSA) was used as a model protein. The effect of fucoidan (1.5, 1.75, 2.0 and 2.5%), chitosan (0.25, 0.50 and 0.75%) and protein (0.25, 0.50 and 0.75%) concentrations, the origin of chitosan and the preparation methods of the particles on the microsphere characteristics were evaluated. METHODS: The microspheres were prepared by a simple method based on the cross-linking of the opposite charged biopolymers. The shape and surface morphologies of the particles were evaluated by scanning electron microscopy (SEM) and the size, charge and encapsulation capacity of the microspheres were determined. The released amount of BSA from the microspheres into phosphate buffered saline (PBS pH 7.4) was determined spectrophotometrically by the Bradford method. SDS-PAGE was performed to check the structural integrity of BSA after the preparation. RESULTS: Smooth and spherical microspheres between the size ranges of 0.61-1.28 microm were obtained. BSA was efficiently encapsulated into the microspheres (51.8-89.5%). All formulation parameters affected the encapsulation capacity of Fucosphere (p < 0.05). The highest encapsulation was obtained with microspheres containing 2.5% of fucoidan (89.5%). CONCLUSIONS: The extent of drug release from the microspheres was dependent on the concentrations of polymers and BSA, chitosan origin and type of preparation method. When the addition methods of protein compared, BSA encapsulated into Fucosphere released slower than the adsorbed protein (E) (p < 0.05). The electrophoretic mobility values of Fucospheres changed between +6.9 and +32.3 mV. In general, BSA release from Fucosphere showed a three-phasic release curve. In conclusion, this new fucoidan microsphere system may be a potential delivery of macromolecular drug such as peptide and protein.

Animals↗

PubMed2006

About mean diameter and size distributions of poly(lactide-co-glycolide) (PLG) microspheres.

Despite the importance of microsphere size for controlled drug delivery, little work has been done to quantitatively predict the distribution of microspheres from manufacturing techniques. This work presents a quantitative study that describes the size distribution of poly(lactide-co-glycolide) (PLG) microspheres. A fluid mechanics based correlation for the mean microsphere diameter is formulated based on the theory of emulsification in turbulent flow under non-coalescing conditions. The correlation was constructed and validated with experimentally obtained mean microsphere diameters prepared at different stirring speeds. In addition, a Rosin Rammler distribution function was found to give an accurate representation of the microsphere distribution. The spread of the microsphere size distribution was found to decrease with stirring speed. With the validation of the mathematical correlation, it is now possible to have a good estimate of the average microsphere size prior to microsphere preparation. This is directly relevant to the pharmaceutical industry where microspheres of specified mean diameter and size distribution are desirable.

Biocompatible Materials↗

PubMedDate not supplied

Ultrasonic atomization for spray drying: a versatile technique for the preparation of protein loaded biodegradable microspheres.

Bovine serum albumin (BDA) loaded microspheres with a spherical shape and smooth surface structure were successfully prepared from poly(lactide-co-glycolide) using an ultrasonic nozzle installed in a Niro laboratory spray dryer. Process and formulation parameters were investigated with respect to their influence on microsphere characteristics, such as particle size, loading capacity, and release properties. Preparation of microspheres in yields of more than 50% was achieved using an ultrasonic atomizer connected to a stream of carrier air. Microsphere characteristics could be modified by changing several technological parameters. An increased polymer concentration of the feed generated larger particles with a significantly reduced initial release of the protein. Moreover, microspheres with a smooth surface structure were obtained from the organic polymer solution with the highest viscosity. Microparticles with a low BSA loading showed a large central cavity surrounded by a thin polymer layer in scanning electron microspheres. A high protein loading led to an enlargement of the shell layer, or even to dense particles without any cavities. A continuous in vitro release pattern of BSA was obtained from the particles with low protein loading. Glass transition temperatures (Tg) of the microspheres before and after lyophilization did not differ from those of the BSA loaded particles prepared by spray drying with a rotary atomizer. Analysis of the polymer by gel permeation chromatography indicated that ultrasonication had no effect on polymer molecular weight. Molecular weight and polydispersity of the pure polymer, placebo microspheres prepared by spray drying, and placebo microspheres prepared using the ultrasonic nozzle were in the same range. In conclusion, ultrasonic atomization represents a versatile and reliable technique for the production of protein loaded biodegradable microspheres without inducing a degradation of the polymer matrix. Particle characteristics can be modified by adjusting formulation parameters and atomization conditions in a simple manner.

Aerosols↗

PubMed2003

Evaluation of PLGA microspheres as delivery system for antitumor agent-camptothecin.

Camptothecin (CPT) and its analogues are a new class of anticancer agents that have been identified over the past several years. Camptothecin exists in two forms depending on the pH: An active lactone form at pH below 5 and an inactive carboxylate form at basic or physiological neutral pH. Poly(lactide-co-glycolide) (PLGA) microspheres have been considered good delivery vehicles for CPT because of acidic microenvironment formed through PLGA degradation. The objective of this study is to investigate antitumor activity of CPT after it is encapsulated in PLGA microspheres. In this study, PLGA microspheres containing various CPT loadings were prepared and characterized. Cytotoxicity of these microspheres to B16 melanoma cells was then evaluated, and uptake of microspheres by B16 cells was also studied. Analysis of drug stability revealed that CPT is released from the microspheres in its active lactone form over the entire release duration. It was also found that there was no interaction between CPT and PLGA matrix within microspheres through Differential Scanning Calorimetry (DSC) and Fourien Transform Infrared Spectroscopy (FT-IR) and hign performance liquid chromatography (HPLC) studies. Cytotoxicity assay showed that CPT encapsulated in PLGA microspheres still retained its antitumor potency. Uptake study revealed quick uptake of the microspheres by B16 cells, which was desirable. It was concluded that PLGA microspheres were suitable delivery vehicles to stabilize and deliver CPT for the treatment of cancer.

Anticarcinogenic Agents↗