Release optimization of epidermal growth factor from PLGA microparticles

Abstract

The objective of this study was to prepare poly lactic-co-glycolic acid (PLGA)-based microparticles as potential carriers for recombinant human epidermal growth factor (rhEGF). In order to optimize characteristic parameters of protein-loaded microspheres, bovine serum albumin (BSA) was selected as the model protein. To reduce burst release as a common problem of microspheres, a proper alteration in the particle composition was used, such as addition of poly vinyl alcohol and changes in initial drug loading. The effects of these parameters on particle size, encapsulation efficiency and in vitro release kinetics of BSA in PLGA microspheres were investigated using a Box–Behnken response surface methodology. The biological activity of the released rhEGF was assessed using human skin fibroblasts cell proliferation assay. The prepared rhEGF-loaded microspheres had an average size of 6.44?±?2.45?µm, encapsulation efficiency of 97.04?±?1.13%, burst release of 13.06?±?1.35% and cumulative release of 22.56?±?2.41%. The proliferation of human skin fibroblast cells cultivated with rhEGF releasate of microspheres was similar to that of pure rhEGF, indicating the biological activity of released protein confirming the stability of rhEGF during microsphere preparation. These results are in agreement with the purpose of our study to prepare rhEGF-entrapped PLGA microparticles with optimized characteristics.     

Biodegradable micro- and nanoparticles as long-term delivery vehicles for gentamicin

Micro- and nanoparticles of poly(lactide-co-glycolide) (PLGA) loading gentamicin were prepared by a solvent evaporation method with the aim of obtaining appropriate vectors for systemic administration. Microspheres presented mean diameters below 3?µm and nanoparticles showed homogeneous sizes with a diameter of 320?nm. Drug loading was more efficient in the case of microencapsulation. The more hydrophilic copolymers with carboxyl-end groups yielded higher microparticle loadings, reaching encapsulation efficiencies up to 9.2?µg?mg^?1 of polymer (502H, 503H or 75:25H). Nanoparticles made of 502H PLGA also achieved an acceptable level of encapsulation (6.2?µg?mg^?1). Particles prepared by using the solvent evaporation method showed no aggregation after hydration, in contrast to the microparticles prepared by spray-drying which showed fast and high auto-aggregation. In vitro release profiles revealed that 503H microspheres showed the highest burst during the first hour, while the most sustained release was for microparticles of 502H copolymer (40% of gentamicin remained in the formulation after 28 days). In summary, microspheres made of 502H, 503H and 75:25H and nanoparticles of 502H showed the best potential properties for systemic use in the treatment of intra-cellular gentamicin-susceptible pathogens.     

5-Fluorouracil-loaded microspheres prepared by spray-drying poly(D,L-lactide) and poly(lactide-co-glycolide) polymers: Characterization and drug release

5-Fluorouracil (5-FU), a hydrosoluble anti-neoplastic drug, was encapsulated in microspheres of poly(D,L-lactide) (PLA) and poly(lactide-co-glycolide) (PLGA) polymers using the spray-drying technique, in order to obtain small size microspheres with a significant drug entrapment efficiency. Drug-loaded microspheres included between 47?±?11 and 67?±?12?µg 5-FU?mg^?1 microspheres and the percentage of entrapment efficiency was between 52?±?12 and 74?±?13. Microspheres were of small size (average diameter: 0.9?±?0.4–1.4?±?0.8?µm microspheres without drug; 1.1?±?0.5–1.7?±?0.9?µm 5-FU-loaded microspheres) and their surface was smooth and slightly porous, some hollows or deformations were observed in microspheres prepared from polymers with larger T_g. A fractionation process of the raw polymer during the formation of microspheres was observed as an increase of the average molecular weight and also of T_g of the polymer of the microspheres. The presence of 5-FU did not modify the T_g values of the microspheres. Significant interactions between the drug and each one of the polymers did not take place and total release of the included drug was observed in all cases. The time needed for the total drug release (28–129?h) was in the order PLA?>?PLGA 75/25?>?PLGA 50/50. A burst effect (17–20%) was observed during the first hour and then a period of constant release rate (3.52?±?0.82–1.46?±?0.26?µg 5-FU?h^?1 per milligram of microspheres) up to 8 or 13?h, depending on the polymer, was obtained.     

Long circulating PEGylated PLGA nanoparticles of cytarabine for targeting leukemia

The present investigation was aimed at developing PEGylated PLGA nanoparticles of cytarabine. PLGA Nanoparticles were prepared by modified nanoprecipitation method, optimized for mean particle size (152?±?6?nm) and entrapment efficiency (41.1?±?0.8%) by a 3² factorial design. The PEGylated PLGA nanoparticles of cytarabine had a zeta potential of ?7.5?±?1.3?mV and sustained the release of cytarabine for 48?h by Fickian diffusion. The IC₅₀ values for L1210 cells were 6.5, 5.3, and 2.2?µM for cytarabine, cytarabine loaded PLGA nanoparticles and cytarabine loaded PLGA-mPEG nanoparticles respectively. Confocal microscopy and flow cytometry showed that the nanoparticles were internalized by the L1210 cells and not simply bound to their surface. Biodistribution studies showed that the PEGylated nanoparticles of cytarabine were present in significantly higher concentrations in blood circulation as well as in brain and bones and avoided RES uptake as compared to the free drug.     

Reduction in burst release after coating poly(D,L-lactide-co-glycolide) (PLGA) microparticles with a drug-free PLGA layer

The high initial burst release of a highly water-soluble drug from poly (D,L-lactide-co-glycolide) (PLGA) microparticles prepared by the multiple emulsion (w/o/w) solvent extraction/evaporation method was reduced by coating with an additional polymeric PLGA layer. Coating with high encapsulation efficiency was performed by dispersing the core microparticles in peanut oil and subsequently in an organic polymer solution, followed by emulsification in the aqueous solution. Hardening of an additional polymeric layer occurred by oil/solvent extraction. Peanut oil was used to cover the surface of core microparticles and, therefore, reduced or prevented the rapid erosion of core microparticles surface. A low initial burst was obtained, accompanied by high encapsulation efficiency and continuous sustained release over several weeks. Reduction in burst release after coating was independent of the amount of oil. Either freshly prepared (wet) or dried (dry) core microparticles were used. A significant initial burst was reduced when ethyl acetate was used as a solvent instead of methylene chloride for polymer coating. Multiparticle encapsulation within the polymeric layer increased as the size of the core microparticles decreased (< 50 µm), resulting in lowest the initial burst. The initial burst could be controlled well by the coating level, which could be varied by varying the amount of polymer solution, used for coating.     

Formulation,characterization and evaluation of cyclodextrin-complexed bendamustine-encapsulated PLGA nanospheres for sustained delivery in cancer treatment

PLGA nanospheres are considered to be promising drug carrier in the treatment of cancer. Inclusion complex of bendamustine (BM) with epichlorohydrin beta cyclodextrin polymer was prepared by freeze-drying method. Phase solubility study revealed formation of A_L type complex with stability constant (Ks?=?645?M^?1). This inclusion complex was encapsulated into PLGA nanospheres using solid-in-oil-in-water (S/O/W) technique. The particle size and zeta potential of PLGA nanospheres loaded with cyclodextrin-complexed BM were about 151.4?±?2.53?nm and???31.9?±?(?3.08)?mV. In-vitro release study represented biphasic release pattern with 20% burst effect and sustained slow release. DSC studies indicated that inclusion complex incorporated in PLGA nanospheres was not in a crystalline state but existed in an amorphous or molecular state. The cytotoxicity experiment was studied in Z-138 cells and IC₅₀ value was found to be 4.3?±?0.11?µM. Cell viability studies revealed that the PLGA nanospheres loaded with complex exerts a more pronounced effect on the cancer cells as compared to the free drug. In conclusion, PLGA nanospheres loaded with inclusion complex of BM led to sustained drug delivery. The nanospheres were stable after 3 months of storage conditions with slight change in their particle size, zeta potential and entrapment efficiency.     

Encapsulation of a pressure-sensitive adhesive by spray-drying: microparticles preparation and evaluation of their crushing strength

An industrial pressure-sensitive adhesive was microencapsulated by spray-drying using an aqueous colloidal ethylcellulose dispersion (Aquacoat® ECD) plasticised by triacetin to form the wall material. Unloaded (0:100) and adhesive-loaded (25:75) particles were produced in a Büchi B-191 mini spray-dryer with product yields of 62% and 57%, respectively. Microparticles were spherical and narrow sized with mean D_3,2 diameters of 3.165?±?0.001 and 5.544?±?0.105?µm, respectively. The microparticles were found to redisperse well in water and exhibit enough stability in neutral and alkaline aqueous media to be further used in a coating slip. Crush tests on single microparticles with diameters ranging from 2 to 12?µm were performed using a nanoindenter. They revealed that the crushing force of both kinds of microparticles increased linearly with their diameter and that the adhesive loading reduced the mechanical strength of the prepared microparticles.     

Topical delivery of urea encapsulated in biodegradable PLGA microparticles: O/W and W/O creams

This study describes the formulation and characterization of O/W and W/O creams containing urea-loaded microparticles prepared with poly (D, L-lactic-co-glycolic acid) (PLGA) in order to encapsulate and stabilize urea. The solvent evaporation method was used for preparing PLGA microparticles containing urea. The microparticles size was evaluated by laser light diffractometry. The resulting microparticles were then incorporated in O/W and W/O creams and stability and the release pattern from the creams was evaluated by UV-spectrophotometry. The particle size of PLGA microparticles was in the range of 1–5 µm and most microparticles had a particle size smaller than 3 µm. The encapsulation efficiency was calculated as 40.5%?±?3.4. This study also examined release pattern of urea which varied among different formulations. The results showed that the release from O/W creams followed Higuchi kinetics while the release from W/O creams showed the zero order kinetics and the creams containing microparticulated urea had slower release than free urea creams.     

Preparation and characterization of biodegradable urea-loaded microparticles as an approach for transdermal delivery

This work describes the formulation and characterization of urea-loaded microspheres prepared using various polymers such as ethyl cellulose (EC), cellulose acetate phthalate (CAP) and poly (D,L-lactic-co-glycolic acid) (PLGA), along with the utilization of a solvent evaporation technique. The effect of various formulation parameters (i.e. polymer type and concentration, vehicle type, polymer solution/vehicle volume ratio, drug/polymer ratio, homogenizer and stirrer speed, sonication time and speed, type of washing solution, drying and separation method) on the characteristics of microspheres was also evaluated. Results obtained indicated that, in the presence of urea, highest rate of EC microsphere production could be obtained at a drug/polymer ratio of 1:2 and a polymer solution/vehicle volume ratio of 1:50. In some cases, crystallization of urea was observed during the encapsulation process using cellulose derivative polymers. CAP microparticles showed a rough and tortuous surface while EC microparticles had a wider range of particle size. However, with the PLGA polymer, much better desired microparticles with a smaller size range of 1–3?µm were obtained. In general, PLGA microspheres were spherical in shape and possessed smooth surfaces with less pores in comparison with those obtained by the other polymers. The yield of particle production and the extent of urea encapsulation in PLGA particles were measured to be 68.87%?±?5.3 and 40.5%?±?3.4, respectively. The release study from PLGA microspheres revealed that up to 70% of the drug was released within a few days, through a four-stage release pattern.     

Improved bioavailability of orally delivered insulin using Eudragit-L30D coated PLGA microparticles

Large porous microparticles of PLGA entrapping insulin were prepared by solvent evaporation method and evaluated in diabetes induced rat for its efficacy in maintaining blood sugar level from a single oral dose. Incorporation of Eudragit L30D (0.03% w/v) in the external aqueous phase resulted in formation of pH responsive enteric coated polymer particles which release most of the entrapped insulin in alkaline pH. At acidic pH, release of insulin from uncoated PLGA microparticles and Eudragit L30D coated PLGA microparticles was 31.62?±?1.8% and 17.5?±?1.29%, respectively, for initial 30 min. However, in 24 h, in vitro released insulin from uncoated PLGA and Eudragit coated particles was 96.29?±?1.01% and 88.30?±?1%, respectively. Released insulin from composite polymer particles were mostly in monomer form without aggregation and was stable for a month at 37°C. Oral administration of insulin loaded PLGA (50 : 50) and Eudragit L30D coated PLGA (50 : 50) microparticles (equivalent to 25 IU insulin/kg of animal weight) in alloxan induced diabetic rats resulted in 37.3?±?11% and 62.7?±?3.8% reduction in blood glucose level, respectively, in 2 h. This effect continued up to 24 h in the case of Eudragit L30D coated PLGA microparticles. Results demonstrate that use of stabilizers during PLGA particle formulation, large porous particle for quick release of insulin and coating with Eudragit L30D resulted in a novel oral formulation for once a day delivery of insulin.     

Encapsulation of low lipophilic and slightly water-soluble dihydroartemisinin in PLGA nanoparticles with phospholipid to enhance encapsulation efficiency and in vitro bioactivity

Context: PLGA nanoparticles have been widely utilised to encapsulate lipophilic drugs for sustained release.

Objective: This study was to enhance encapsulation efficiency and drug loading for the poorly lipophilic drug dihydroartemisinin (DHA) in PLGA nanoparticles, where amphiphilic phospholipid was employed as the intermediate. Materials and methods: DHA-phospholipid complex formulation was optimised using the response surface method. DHA-phospholipid complex-nanoparticles (DHA-PLC-NPs) were prepared using the solvent evaporation method. Results: The particle size, zeta potential, entrapment efficiency and drug loading of the nanoparticles were 265.3?±?7.9?nm, ?21.4?±?6.3?mV, 74.2?±?6.5% and 2.80?±?0.35%, respectively. Compared with the rapidly released free form, DHA underwent sustained release from the nanoparticles. DHA-PLC-NPs presented stronger cell proliferative inhibition than DHA treatment alone and apoptosis was obviously induced after DHA-PLC-NPs treatment. Conclusion: Phospholipid complexes are useful intermediate to improve the lipophilicity of drugs, the interaction with the hydrophobic core of PLGA and the encapsulation efficiency of poorly lipophilic drugs in polymeric nanoparticles.     

Preparation and characterization of textile-based carrier systems for anal fissure treatment

Anal fissure is common and painful disease of anorectum. In this study, microparticles containing nifedipine and lidocaine HCl were prepared by spray drying and applied to bio-degradable and bio-stable tampons. Characterization of microparticles was determined by visual analyses, mass yield, particle size measurement, encapsulation efficiency, drug loading and in vitro drug release. Mass yield was between 5.5 and 45.9%. The particle size was between 15.1 and 26.8?µm. Encapsulation efficiency were 96.142?±?5.931 and 85.571?±?3.301; drug loading were 65.261?±?3.914% and 37.844?±?4.339% of L2 and N1, respectively. Well-separated, mainly spherical microparticles with suitable properties were obtained. Optimum microparticles were applied to tampons. Physical properties and visual characteristics of tampons were investigated before and after binder application. In vitro drug release from tampons were also examined. According to the results, textile-based carrier systems loaded microparticles containing nifedipine and lidocaine HCl will be an effective and promising alternative for current anal fissure treatment.     

Preparation and characterization of D,L-PLA loaded 17-β-Estradiol valerate by emulsion/evaporation methods

PLA microparticles containing 17-β-estradiol valerate were prepared by an emulsion/evaporation method in order to sustain drug release. This system was characterized concerning particle size, particle morphology and the influence of formulation and processing parameters on drug encapsulation and in vitro drug release. The biodegradation of the microparticles was observed by tissue histological analysis. Scanning electron microscopy and particle size analysis showed that the microparticles were spherical, presenting non-aggregated homogeneous surface and had diameters in the range of 718–880 nm (inert micro-particles) and 3–4 µm (drug loaded microparticles). The encapsulation efficiency was ～80%. Hormone released from microparticles was sustained. An in vivo degradation experiment confirmed that microparticles are biodegradable. The preparation method was shown to be suitable, since the morphological characteristics and efficiency yield were satisfactory. Thus, the method of developed microparticles seems to be a promising system for sustained release of 17-β-estradiol.     

PLGA nanoparticles for the oral delivery of nuciferine: preparation,physicochemical characterization and in vitro/in vivo studies

This article reports a promising approach to enhance the oral delivery of nuciferine (NUC), improve its aqueous solubility and bioavailability, and allow its controlled release as well as inhibiting lipid accumulation. NUC-loaded poly lactic-co-glycolic acid nanoparticles (NUC-PLGA-NPs) were prepared according to a solid/oil/water (s/o/w) emulsion technique due to the water-insolubility of NUC. PLGA exhibited excellent loading capacity for NUC with adjustable dosing ratios. The drug loading and encapsulation efficiency of optimized formulation were 8.89?±?0.71 and 88.54?±?7.08%, respectively. NUC-PLGA-NPs exhibited a spherical morphology with average size of 150.83?±?5.72?nm and negative charge of ?22.73?±?1.63?mV, which are suitable for oral administration. A sustained NUC released from NUC-PLGA-NPs with an initial exponential release owing to the surface associated drug followed by a slower release of NUC, which was entrapped in the core. In addition, ～77?±?6.67% was released in simulating intestinal juice, while only about 45.95?±?5.2% in simulating gastric juice. NUC-PLGA-NPs are more efficient against oleic acid (OA)-induced hepatic steatosis in HepG₂ cells when compared to naked NUC (n-NUC, *p < 0.05). The oral bioavailability of NUC-PLGA-NPs group was significantly higher (**p < 0.01) and a significantly decreased serum levels of total cholesterol (TC), triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C), as well as a higher concentration of high-density lipoprotein cholesterol (HDL-C) was observed, compared with that of n-NUC treated group. These findings suggest that NUC-PLGA-NPs hold great promise for sustained and controlled drug delivery with improved bioavailability to alleviating lipogenesis.     

Preparation and evaluation of PLGA microparticles as carrier for the pulmonary delivery of rhIL-2 : I. Effects of some formulation parameters on microparticle characteristics

In this study, recombinant human interleukin-2 (rhIL-2) containing poly(lactic-co-glycolic acid) (PLGA) microparticles were prepared for pulmonary administration by modified w/o/w double emulsion solvent extraction method and the effects of various formulation parameters on the physicochemical properties of the microparticles were investigated. Microparticles in suitable size for pulmonary administration (4.02?µm) were obtained by increasing dichloromethane volume used in the organic phase. Also, a very high encapsulation efficiency (99.22%) value could be reached in these microparticles. In the sodium dodecyl sulphate-polyacrylamide gel electrophoresis analysis, rhIL-2 extracted from microparticles having a similar band with native rhIL-2 showed that the protein was not affected by the encapsulation process. The release curves of microparticles exhibited a biphasic fashion, characterized by a fast release phase at initial 1 day, followed by a slower one on the remaining days. Bioactivity investigations using T cells show that rhIL-2 encapsulated in PLGA microparticles retain their biological activity.     

Nanoparticle-based topical ophthalmic formulation for sustained release of stereoisomeric dipeptide prodrugs of ganciclovir

Poly(d,l-lactic-co-glycolic acid) (PLGA) nanoparticles (NP) of Val-Val dipeptide monoester prodrugs of ganciclovir (GCV) including L-Val-L-Val-GCV (LLGCV), L-Val-D-Val-GCV (LDGCV) and D-Val-L-Val-GCV (DLGCV) were formulated and dispersed in thermosensitive PLGA-PEG-PLGA polymer gel for the treatment of herpes simplex virus type 1 (HSV-1)-induced viral corneal keratitis. Nanoparticles containing prodrugs of GCV were prepared by a double-emulsion solvent evaporation technique using various PLGA polymers with different drug/polymer ratios. Nanoparticles were characterized with respect to particle size, entrapment efficiency, polydispersity, drug loading, surface morphology, zeta potential and crystallinity. Prodrugs-loaded NP were incorporated into in situ gelling system. These formulations were examined for in vitro release and cytotoxicity. The results of optimized entrapment efficiencies of LLGCV-, LDGCV- and DLGCV-loaded NP are of 38.7?±?2.0%, 41.8?±?1.9%, and 45.3?±?2.2%; drug loadings 3.87?±?0.20%, 2.79?±?0.13% and 3.02?±?0.15%; yield 85.2?±?3.0%, 86.9?±?4.6% and 76.9?±?2.1%; particle sizes 116.6?±?4.5, 143.0?±?3.8 and 134.1?±?5.2?nm; and zeta potential ?15.0?±?4.96, ?13.8?±?5.26 and ?13.9?±?5.14?mV, respectively. Cytotoxicity studies suggested that all the formulations are non-toxic. In vitro release of prodrugs from NP showed a biphasic release pattern with an initial burst phase followed by a sustained phase. Such burst effect was completely eliminated when NP were suspended in thermosensitive gels with near zero-order release kinetics. Prodrugs-loaded PLGA NP dispersed in thermosensitive gels can thus serve as a promising drug delivery system for the treatment of anterior eye diseases.     

NSAID Drugs Release from Injectable Microspheres Produced by Supercritical Fluid Emulsion Extraction

Supercritical fluid emulsion extraction is an innovative technology that uses supercritical carbon dioxide (SC‐CO₂) to extract the dispersed oily phase of an emulsion. This technology was used to produce poly‐lactic‐co‐glycolic acid (PLGA) microspheres charged with two common NSAIDs: piroxicam (PX) and diclophenac sodium (DF). Single (O/W) and double (W/O/W) emulsions were tested and a comparative study between the characteristics of the microspheres obtained by SC‐CO₂ extraction and the ones produced by conventional solvent evaporation (SE) is proposed. Varying the droplet dimensions, microspheres with mean diameters (MDs) of 1, 2, and 3 µm were obtained; however, the microspheres produced by SC‐CO₂ gave always a better reproduction of the MD of original droplets because aggregation phenomena often modify the mean size and distribution of the microparticles produced by SE. Moreover, very efficient drug loadings (88% w/w of DF in PLGA using W/O/W emulsion and 97% of PX w/w in PLGA starting from O/W emulsion) were measured in the products obtained by SC‐CO₂, respectively; whereas, the SE produced a drug loading of 30% in the case of double emulsion and of 70% for single emulsion. Solvent residue of 10 ppm was also measured by SC‐CO₂ technology against the 600 ppm of the SE products. The release profiles of the entrapped drugs were also monitored to check the structure of the microspheres produced by this new technology. © 2009 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 99: 1484–1499, 2010     

A “drug cocktail” delivered by microspheres for the local treatment of rat glioblastoma

For the treatment of glioblastoma multiforme, an “anticancer drug cocktail” delivered by biodegradable poly-lactide-co-glycolide (PLGA)-microspheres is proposed. Celecoxib, etoposide, and elacridar were encapsulated by an oil/water emulsification solvent evaporation method. Drug-loaded microspheres were analyzed for their physicochemical properties and evaluated in a rat glioblastoma model. Microspheres had a mean diameter 10–20?µm, and encapsulation rates varied upon lipophilicity of the drug (celecoxib: 97.4?±?0.4%; elacridar: 98.1?±?0.3%; and etoposide: 38.7?±?8.3%). Drug release of celecoxib and elacridar resulted in a burst (t50: 3.1?h and 1.0?h, respectively) while etoposide release was slower (t50: 45.3?h). The comparison of celecoxib (p?=?0.021) and etoposide microspheres (p?=?0.002) as well as their combination (p?=?0.011) led to a significant increase in the probability of survival compared to blank microspheres. Local delivery of celecoxib and etoposide microspheres was found to be suitable for the treatment of glioblastoma in rats although simultaneous drug administration did not improve the therapeutic outcome.     

The preparation of sustained release erythropoietin microparticle

Purpose: Protein microencapsulation in biodegradable polymers is a promising route to provide for sustained release. The erythropoietin (EPO) microparticles are using human serum albumin (HSA) and poly-L-lysine (PK) as the protection complex to increased EPO integrity, entrapped efficiency and active EPO release by w/o/w solvent evaporation techniques. The optimum formulation development process was also reported by using FITC-OVA as a model protein.

Methods: The model protein FITC-ovalbumin and EPO are protected by human serum albumin and poly-L-lysine complex and encapsulated in 50:50 poly(DL-lactide-co-glycolide) by a w/o/w solvent evaporation method. Protein active integrity and degradation compound is measured by size-exclusion chromatography. Protein-loaded microparticle physical properties and in vitro active and degradation compounds release profile are characterized.

Results: High active integrity protein loading efficiency and particle yield of EPO or OVA-HSA/PK-loaded PLG microparticles are successfully produced by a w/o/w solvent evaporation method. Varied protection protein complex formulations and encapsulation processes are investigated. The high OVA model protein loading efficiency (80.2%), FITC-OVA content (0.24?µg?mg^?1) and yield (72.4%) are obtained by adding 100?µg?mL^?1 FITC-OVA complex with 10% HSA/0.05% PK (Mw 1.5–3?kD) in the initial solution to protect the model protein. In vitro release profiles show more active OVA release from HSA/PK OVA-loaded than OVA-loaded only microparticles and also the amount of degraded protein that comes out after 3 weeks incubated in the PBS medium for OVA-loaded only microparticles is observed. The same formulation and preparation process resulted in EPO loading efficiency (68.4%), EPO content (0.23?µg?mg^?1) and yield (76.1%) for HSA/PK EPO-loaded microparticles. In vitro release profiles show active EPO sustained release over 7 days. Using HSA/PK as carried in the primary emulsion of EPO-loaded microparticles resulted in less burst release% than EPO-loaded only microparticles.     

Microparticulated systems based on chitosan and poly(vinyl alcohol) with potential ophthalmic applications

Abstract

Spherical microparticles for encapsulation of drugs for the treatment of diseases, with a diameter ranging between 2 and 4?µm, were obtained by double crosslinking (ionic and covalent) of chitosan and poly(vinyl alcohol) blend in a water-in-oil emulsion. Microparticles characterisation was carried out in terms of structural, morphological and swelling properties in aqueous media. The presence of chitosan in particles composition confers them a pH-sensitive character. Toxicity and hemocompatibility tests prove the biocompatible character of microparticles. The pilocarpine loading capacity is high as well as the release efficiency which increases up to 72 and 82% after 6?h. The obtained results recommend the microparticles as sustained release drug carriers for the treatment of eye diseases.