Evaluation of sucrose esters as alternative surfactants in microencapsulation of proteins by the solvent evaporation method (original) (raw)
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Journal of Microencapsulation, 1999
T he aim of this work was to optimize protein entrapment in pure poly("caprolactone) (PCL) microparticles (MP) using the (water-in-oil)-in water solvent evaporation technique and bovine serum albumin (BS A) as drug model. T herefore, the preparative variables such as polymer solvent, protein/polymer ratio, polymer molecular weight, internal aqueous/organic phases ratio, organic/ external aqueous phase ratio, and nature of the emulsi® er were evaluated on microparticle characteristics such as BS A entrapment, entrapment e ciency, size and morphology. T he in v itro release pro® les of BS A from such MP in two di erent media with or without sodium dodecyl sulphate (SDS) were investigated. In optimum conditions, smooth and spherical pure PCL MP with high encapsulation e ciency (50. 29 5.01%) were prepared. T he release pro® les of BSA in the release media were signi® cantly di erent and faster in the presence of SDS. Moreover, they exhibited a relatively low burst e ect after 24 h (< 30%) followed by a continuous release over 28 days. Due to PCL ' s numerous desirable characteristics, such MP could be an exciting alternative for the controlled release of proteinaceous compounds.
Journal of Controlled …, 1994
Poly (lactide-co-glycolide) microparticles, containing ricin toxoid or fluorescein isothiocyanate-labeled bovine serum albumin were prepared by a water-in-oil-in-water emulsion solvent extraction procedure with a high encapsulation efficiency (from 60% to 94%). Three agitation methods: vortex mixing, homogenization and sonication, were used to make the first inner w/o emulsion and the second w/o/w emulsion. The effects of process parameters on structure, surface condition, particle size, core loading and in vitro release properties of the protein-loaded microparticles were studied. SDS-PAGE analysis showed that none of the agitation methods damaged the structural integrity and stability of the encapsulated protein. Confocal laser scanning microscopic analysis and in vitro studies indicated that heterogeneous microparticles provided a fast release profile with a large protein burst (62%). and homogeneous microparticles released protein slower with a much lower protein burst (7%). These properties may influence the dynamics of the antibody response.
Development of double emulsion nanoparticles for the encapsulation of bovine serum albumin
Colloids and surfaces. B, Biointerfaces, 2017
In the present work, a double emulsion was developed for the encapsulation of Bovine Serum Albumin (BSA) as a model protein for the future encapsulation of viral proteins. The first emulsion polydispersity index (PDI) was studied with increasing concentrations of poly (ε-caprolactone) (PCL) as stabilizer (from 16% w/v to 5% w/v) and polyvinyl alcohol (PVA) as the surfactant in the second emulsion at 1.5% w/v. Results suggest that at decreasing concentrations of PCL the PDI of the emulsion also decrease, indicating that viscosity of the emulsion is crucial in the homogeneity of the resultant size distribution of the nanoparticles. When PVA concentration in the second emulsion was increased from 1.5% w/v to 2.5% w/v the PDI also increased. To study the relationship between the structure of the surfactant in the second emulsion and the resultant BSA encapsulation, emulsions were prepared with Pluronic F68 and PVA both at 1.5% w/v and PCL in the first emulsion at 5% w/v. Results indicat...
Microemulsions for protein delivery: loading optimization and stability
Current pharmaceutical biotechnology, 2017
Microemulsions are attractive delivery systems for therapeutic proteins and peptides due to their ability to enhance bioavailability. Although different proteins and peptides have been successfully delivered through such ternary systems, no information can be found about protein loading and the formulation stability when such microemulsions are prepared with pharmaceutically-approved oils and surfactants. The aim of this work was to optimise a ternary system consisting of water/ethyl oleate/Span 80-Tween 80 and to determine its protein loading capacity and stability, using bovine serum albumin (BSA) as a model of biomolecule. The optimization was carried out using a Central Composite Design and all the prepared formulations were characterised through dynamic light scattering, rheology, optical and polarized microscopy. Subsequently, the maximum loading capacity was determined and the stability of the final microemulsion with the highest content of protein was followed over six mon...
Journal of Pharmacy and Pharmacology, 2001
Bovine serum albumin (BSA) was encapsulated into poly(lactide-co-glycolide) (PLG) microspheres by a solid-in-oil-in-water (s/o/w) technique. We tested whether perturbations in BSA secondary structure could be minimized during encapsulation by using trehalose and how this would influence BSA aggregation and release. BSA secondary structure was monitored noninvasively by Fourier-transform infrared spectroscopy. When BSA was co-lyophilized with trehalose, lyophilization-induced structural perturbations were significantly reduced. The formulation obtained (BSA-Tre) was encapsulated into PLG microspheres and, by optimizing critical encapsulation parameters, a loading efficiency of 85 % was achieved. However, due to the loss of the excipient in the o/w emulsion step, the structure of BSA-Tre was more perturbed than before encapsulation. Excipient-loss and encapsulation-induced structural perturbations could be prevented by saturating the aqueous phase in the o/w step with trehalose and by using the organic solvent chloroform. This in turn reduced the formation of soluble BSA aggregates.
Protein delivery using nanoparticles based on microemulsions with different structure-types
European Journal of Pharmaceutical Sciences, 2008
Poly(alkylcyanoacrylate) nanoparticles based on microemulsions with different structuretypes and containing insulin as a model protein were prepared and characterised in this study. A phase diagram of the pseudoternary system isopropyl myristate, caprylocaproyl macrogolglycerides, polyglycerol oleate and water was established. All compounds used in this study were pharmaceutically acceptable and biocompatible. The area in the phase diagram containing optically isotropic, monophasic systems was designated as the microemulsion region. Systems within this region were identified as water-in-oil (w/o), bicontinuous and oil-in-water (o/w) microemulsions with viscosity, conductivity, differential scanning calorimetry and self-diffusion NMR. The size distributions of the resulting nanoparticles prepared by interfacial polymerisation from selected microemulsions using ethyl (2) cyanoacrylate and butyl (2) cyanoacrylate were unimodal but template-and monomer-dependent and ranged from 160 to 400 nm. Entrapment and release of insulin were also studied. Entrapment ranged from 11.5 to 20.9% and a near zero-order release was observed after an initial burst. Release of insulin was monitored for 6 h. Insulinloaded nanoparticles were 320-350 nm in size. The microemulsion-structure was retained during the polymerisation process as determined by NMR. This study showed that these microemulsions with flexible formulation possibilities for the solubilisation of peptides and proteins depending on their microstructure could serve well as a platform for designing encapsulation processes for oral delivery of insulin.
Molecular Pharmaceutics, 2006
A new microencapsulation technique based on the solvent exchange method was implemented using an ultrasonic atomizer system to encapsulate a protein drug in mild conditions. The reservoir-type microcapsules encapsulating lysozyme as a model protein were prepared by inducing collisions between the aqueous droplets containing lysozyme and the droplets of organic solvent with dissolved poly(lactic acid-co-glycolic acid) (PLGA).The main focus of the study was to examine formulation variables on the size and the encapsulation efficiency of the formed microcapsules. The formulation variables examined were concentrations of mannose in the aqueous cores, NaCl in the aqueous collection medium, and PLGA in organic solvent. The mean diameter of the microcapsules ranged from 40 µm to 100 µm. Smaller microcapsules showed lower encapsulation efficiencies. The resulting microcapsules released native lysozyme in a sustained manner, and the release rate was dependent on the formulation conditions, such as the concentration and molecular weight of the polymer used. The solvent exchange method does not induce lysozyme aggregation and loss of its biological activity. The solvent exchange method, implemented by the ultrasonic atomizer system, provides an effective tool to prepare reservoir-type microcapsules for delivering proteins. . † Present address: Department of Advanced Polymer and Fiber Materials, Kyung Hee University, Gyeonggi-do 449-701, South Korea. (1) Bartus, R. T.; Tracy, M. A.; Emerich, D. F.; Zale, S. E. Sustained delivery of proteins for novel therapeutic agents. Science 1998, 281, 1161-1162. (2) Sinha, V. R.; Trehan, A. Biodegradable microspheres for protein delivery. J. Controlled Release 2003, 90, 261-280. (3) Tamber, H.; Johansen, P.; Merkle, H. P.; Gander, B. Formulation aspects of biodegradable polymeric microspheres for antigen delivery.
Advanced Materials, 2011
Proteins and other biomolecules sequestered in and delivered from polymeric drug delivery systems (DDS) undergo several process and storage-related stresses throughout the life of the product that can result in significant degradation, loss of bioactivity and raise safety concerns. [1-4] Process-related stresses during manufacturing of drug delivery systems can lead to significant protein degradation. These stresses can include elevated temperatures, exposure to liquid and solid hydrophobic interfaces, and vigorous mechanical agitation. [1, 5, 6] A number of approaches have been developed to ameliorate the impact of individual stresses in emulsion-based methods. These include the use of interface stabilizers, [7, 8] protein crystalization [9] and covalent protein modification. [10] Ideally a single approach would protect against all these stresses, yielding excellent encapsulation efficiency and storage stability, while giving burst-free sustained release for any protein and polymer system of interest. Far from meeting this ideal, many approaches for improving one aspect of performance are neutral or deleterious to others. For example, solid-in-oil-in-water (s-o-w) emulsions [3] expose the protein to less solvent-based stress than do water-in-oil-inwater (w-o-w) methods; however, so -w methods have thus far led to reduced encapsulation efficiency or significant burst release. So -w vehicles incorporate proteins as a solid phase through freeze-drying or related processes, allowing inclusion of buffer salts, sugars, and other stabilizing additives. However, bulk freeze-drying yields relatively large protein
Journal of Pharmacy and Pharmacology, 2001
Non-aqueous protocols to encapsulate pharmaceutical proteins into biocompatible polymers have gained much attention because they allow for the minimization of procedure-induced protein structural perturbations. The aim of this study was to determine if these advantages could be extended to a semi-aqueous encapsulation procedure, namely the solid-in-oil-inwater (s/o/w) technique. The model protein bovine serum albumin (BSA) was encapsulated into poly(lactide-co-glycolide) (PLG) microspheres by first suspending lyophilized BSA in methylene chloride containing PLG, followed by emulsification in a 1 % aqueous solution of poly(vinyl alcohol). By variation of critical encapsulation parameters (homogenization intensity, BSA :PLG ratio, emulsifier concentration, ratio of organic to aqueous phase) an encapsulation efficiency of 90 % was achieved. The microspheres obtained showed an initial burst release of 20 %, a sustained release over a period of about 19 days, and a cumulative release of at least 90 % of the encapsulated BSA. Different release profiles were observed when using different encapsulation protocols. These differences were related to differences in the microsphere erosion observed using scanning electron microscopy. Release of BSA was mainly due to simple diffusion or to both diffusion and microsphere erosion. Fourier-transform infrared studies were conducted to investigate the secondary structure of BSA during the encapsulation. Quantification of the α-helix and β-sheet content as well as of overall structural changes showed that the secondary structure of encapsulated BSA was not more perturbed than in the lyophilized powder used initially. Thus, the encapsulation procedure did not cause detrimental structural perturbations in BSA. In summary, the results demonstrate that the s/o/w technique is an excellent alternative to the water-in-oil-in-water technique, which is still mainly used in the encapsulation of proteins in PLG microspheres.