Blend Microparticles Research Articles

PBPK modelling of ceftriaxone Na-loaded starch-sodium alginate polymeric blend prepared by water-in-oil emulsification for oral delivery

Ceftriaxone is a third-generation cephalosporin antibiotic effective against many bacterial infections. However, owing to its instability in the gastrointestinal tract (GIT), it is administered by injections, which is an unfavourable route of administration. Therefore, the aim of this study was to formulate ceftriaxone into biodegradable and thermally stable polymeric blend microparticles that are suitable for oral delivery. The drug-loaded microparticles were prepared by the water-in-oil (W/O) emulsion method and consisted of starch and sodium alginate (NaAlg) as a polymeric matrix and glutaraldehyde (GA) as a cross-linking agent. Characterization of these particles using scanning electron microscopy (SEM) showed that the particles were spherical in shape with a smooth surface. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) of these particles showed no drug-polymer interactions. The highest percentage yield of particles was obtained at 3% polymer concentration. The particle size increased slightly after drug loading. The drug loading and entrapment efficiency appeared to increase with increasing polymer concentration. In vitro drug release at pH 1.2 and pH 7.4, revealed that drug release was below 20% at the acidic pH, while at pH 7.4, drug release of up to 85% was observed. The release mechanism followed first-order and Fickian diffusion patterns. Plasma concentration-time profiles were simulated for subcontinental Asian populations using commercial PBPK software, and the results suggest that microencapsulation of ceftriaxone sodium in a polymeric blend could represent a promising approach for controlled oral delivery of the drug, with enhanced absorption and bioavailability of the drug.

Effect of coconut coir and regenerated silk microparticles as blends and natural binders for construction and demolition waste (CDW) wood on the mechanical, thermal, and structural properties of biomicrocomposites prepared by hot-pressing

This study aims to utilize the thermosetting behavior of native lignin and the self-assembly of silk in coconut coir (CC) and regenerated silk (RS) microparticles used as blends and natural binders for construction and demolition waste (CDW) wood and their effect on the mechanical, thermal, and structural properties of CDW wood/CC, RS/CC, and CDW wood/RS biomicrocomposites. The obtained biomicrocomposites were prepared by hot-pressing blended microparticles at weight ratios of 80:20, 60:40, 50:50, 40:60, and 20:80 in the temperature range of 170–180°C. The obtained biomicrocomposites were characterized by bending strength, water resistance, scanning electron microscopy (SEM), thermogravimetric analysis/derivative thermogravimetry (TGA/DTG), and attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) measurements. Findings showed that the incorporation of RS displayed superior enhancement in the mechanical properties and water resistance in CDW/RS. The incorporation of CC slightly improved these properties in CDW/CC and RS/CC but offered greater thermal stability, as shown by thermogravimetric analysis (TGA/DTG). The addition of RS and CC showed good interfacial adhesion, as revealed by SEM. FTIR data revealed strong reactivity among CC, RS, and CDW wood.

Biomaterial microparticles of keratose/collagen blend prepared by a water-in-oil emulsification–diffusion method

This work aimed to explore optimal conditions for keratose (KR), collagen (CL), and KR/CL blend microparticles preparation using a water-in-oil emulsion solvent diffusion method. The protein solution was used as the water phase (W) and ethyl acetate was used as the oil phase (O). Scanning electron microscopy (SEM) results indicated that most of the KR microparticles were hollow, with a rough and dented outer surface while CL microparticles had variable shapes with smooth surfaces and some small pores distributed inside the particles. Morphology of the KR/CL blend microparticles varied according to types of polymer, mass ratio, and the condition used. All particles had as main structure, an α-helix co-existing with random coil structures. The decomposition steps of the KR and CL microparticles followed similar trends while the Td, max of blend particles varied at different mass ratios of KR and KL. The high content of CL influenced the formation of a dense texture of the blend microparticles. The prepared microparticles showed a drug-controlled release profile that could be applied as a drug delivery system.

Preparation and Characterization of Keratin/Alginate Blend Microparticles

The water‐in‐oil (W/O) emulsification‐diffusion method was used for construction of keratin (Ker), alginate (Alg), and Ker/Alg blend microparticles. The Ker, Alg, and Ker/Alg blend solutions were used as the water phase, while ethyl acetate was used as the oil phase. Firstly, different concentrations of Ker solution was used to find suitable content. 1.6% w/v Ker solution was blended with the same concentration of the Alg solution for further microparticle construction. Results from scanning electron microscope analysis show that the microparticles have different shapes: spherical, bowl‐like, porous, and hollow, with several sizes depending on the blend ratio. FTIR and TG analyses indicated that the secondary structure and thermal stability of the microparticles were influenced by the Ker/Alg blend ratio. The interaction between functional groups of keratin and alginate was the main factor for both β‐sheet structure and Td,max values of the microparticles. The results suggested that Ker/Alg blend microparticles might be applied in many fields by varying the Ker/Alg ratio.

Chitosan/Silk Sericin Blend Microparticles Prepared by Water-in-Oil Emulsification-Diffusion for Controlled Release of Silk Sericin Antioxidant

This study aimed to develop the novel drug delivery carriers to control the release of silk sericin antioxidant. The chitosan/silk sericin blend microparticles were successfully prepared by the water-in-oil emulsification-diffusion method. Influence of silk sericin ratio on characteristics and in vitro silk sericin release behaviors of the blend microparticles was investigated. All the spherical-shaped blend microparticles had an average size of 41 – 48 m and could load the silk sericin in high loading efficiency (69 – 75%). The FTIR and thermogravimetric results indicated the blend microparticles with different silk sericin contents can be prepared by varying the silk sericin feed ratio. The blend microparticles exhibited sustained release profiles of the silk sericin. The in vitro silk sericin release content increased as the silk sericin ratio increased. Antioxidant activities of the blend microparticles assessed by FRAP assay were more than the neat chitosan microparticles and steadily increased with the silk sericin ratio. The results demonstrated that the chitosan/silk sericin blend microparticles prepared by the water-in-oil emulsification-diffusion method should be useful drug delivery carriers for the controlled release silk sericin antioxidant.

Formulation and characterization of poly(propylacrylic acid)/poly(lactic-co-glycolic acid) blend microparticles for pH-dependent membrane disruption and cytosolic delivery.

Poly(lactic-co-glycolic acid) (PLGA) is widely used as a vehicle for delivery of pharmaceutically relevant payloads. PLGA is readily fabricated as a nano- or microparticle (MP) matrix to load both hydrophobic and hydrophilic small molecular drugs as well as biomacromolecules such as nucleic acids and proteins. However, targeting such payloads to the cell cytosol is often limited by MP entrapment and degradation within acidic endolysosomes. Poly(propylacrylic acid) (PPAA) is a polyelectrolyte polymer with the membrane disruptive capability triggered at low pH. PPAA has been previously formulated in various carrier configurations to enable cytosolic payload delivery, but requires sophisticated carrier design. Taking advantage of PPAA functionality, we have incorporated PPAA into PLGA MPs as a simple polymer mixture to enhance cytosolic delivery of PLGA-encapsulated payloads. Rhodamine loaded PLGA and PPAA/PLGA blend MPs were prepared by a modified nanoprecipitation method. Incorporation of PPAA into PLGA MPs had little to no effect on the size, shape, or loading efficiency, and evidenced no toxicity in Chinese hamster ovary epithelial cells. Notably, incorporation of PPAA into PLGA MPs enabled pH-dependent membrane disruption in a hemolysis assay, and a three-fold increased endosomal escape and cytosolic delivery in dendritic cells after 2 h of MP uptake. These results demonstrate that a simple PLGA/PPAA polymer blend is readily fabricated into composite MPs, enabling cytosolic delivery of an encapsulated payload. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1022-1033, 2018.

Preparation, characterization and in vitro evaluation of ε-polylysine-loaded polymer blend microparticles for potential pancreatic cancer therapy

Peptide active ingredients show great promise regarding the treatment of various health-endangering diseases. It is reported that L-lysine inhibits the proliferation of several tumour lines in vitro and in vivo. However, proteins and peptide drugs possess certain disadvantages such as in vivo instability and short biological half-life. On the grounds that drug delivery systems can overcome a wide spectrum of bioactive compounds issues, a biopolymeric blend-based microparticulated system capable of delivering ε-polylysine (PLL) was developed. PLL-loaded poly((L)Lactic acid)/poly(D,L-Lactide)-co-poly(ethylene glycol)-based microparticles (PLL-PB-MPs) were prepared and fully characterised exhibiting a narrow size distribution (1.2 ± 0.12 µm), high loading efficiency (81%) and improved thermal stability (Td from 250 °C to 291 °C). The cytotoxicity and antiproliferative effect of PLL-PB-MPs in pancreatic adenocarcinoma cell lines BxPC3 and MIA PaCa-2 were confirmed. Due to their physicochemical and biopharmaceutical properties, PB-MPs constitute a promising carrier to deliver bioactive peptides.

Poly(2-propylacrylic acid)/poly(lactic-co-glycolic acid) blend microparticles as a targeted antigen delivery system to direct either CD4+ or CD8+ T cell activation.

Poly(lactic‐co‐glycolic acid) (PLGA) based microparticles (MPs) are widely investigated for their ability to load a range of molecules with high efficiency, including antigenic proteins, and release them in a controlled manner. Micron‐sized PLGA MPs are readily phagocytosed by antigen presenting cells, and localized to endosomes. Due to low pH and digestive enzymes, encapsulated protein cargo is largely degraded and processed in endosomes for MHC‐II loading and presentation to CD4+ T cells, with very little antigen delivered into the cytosol, limiting MHC‐I antigenic loading and presentation to CD8+ T cells. In this work, PLGA was blended with poly(2‐propylacrylic acid) (PPAA), a membrane destabilizing polymer, in order to incorporate an endosomal escape strategy into PLGA MPs as an easily fabricated platform with diverse loading capabilities, as a means to enable antigen presentation to CD8+ T cells. Ovalbumin (OVA)‐loaded MPs were fabricated using a water‐in‐oil double emulsion with a 0% (PLGA only), 3 and 10% PPAA composition. MPs were subsequently determined to have an average diameter of 1 µm, with high loading and a release profile characteristic of PLGA. Bone marrow derived dendritic cells (DCs) were then incubated with MPs in order to evaluate localization, processing, and presentation of ovalbumin. Endosomal escape of OVA was observed only in DC groups treated with PPAA/PLGA blends, which promoted high levels of activation of CD8+ OVA‐specific OT‐I T cells, compared to DCs treated with OVA‐loaded PLGA MPs which were unable activate CD8+ T cells. In contrast, DCs treated with OVA‐loaded PLGA MPs promoted OVA‐specific OT‐II CD4+ T cell activation, whereas PPAA incorporation into the MP blend did not permit CD4+ T cell activation. These studies demonstrate PLGA MP blends containing PPAA are able to provide an endosomal escape strategy for encapsulated protein antigen, enabling the targeted delivery of antigen for tunable presentation and activation of either CD4+ or CD8+ T cells.

Preparation of regenerated silk sericin/silk fibroin blend microparticles by emulsification–diffusion method for controlled release drug delivery

ABSTRACTThis study reports drug-loaded silk sericin (SS)/silk fibroin (SF) blend microparticles being fabricated by the water-in-oil emulsion solvent diffusion of a SS/SF aqueous blend solution. Blue dextran was used as the water-soluble drug model. The influence of the SS/SF blend ratio on the characteristics and drug release behavior of the blend microparticles was investigated. The blend microparticles were analyzed by scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, thermogravimetric analysis (TGA) and UV-vis spectroscopy. The blend microparticles were nearly spherical in shape as determined from SEM micrographs. The FTIR and TG results demonstrated that interactions between SS and SF molecules had occurred. The blend microparticles showed very high drug loading efficiency (94–98%) for all blend ratios. The in vitro drug release significantly decreased with decreasing SS blend ratio. The results demonstrated that the SS/SF blend microparticles could be used as biocompatible and biodegradable microparticles for controlled release drug delivery applications.

Biodegradable silk fibroin/chitosan blend microparticles prepared by emulsification-diffusion method

AbstractIn this study, biodegradable microparticles of silk fibroin (SF)/chitosan (CS) blends with SF/CS blend ratios of 1:0, 2:1, 1:1, 1:2 and 0:1 (w/w) were prepared using the water-in-oil emulsification-diffusion method without any surfactants. An aqueous SF/CS blend solution and ethyl acetate were used as the water and oil phases, respectively. The plain SF had an irregular shape, while the CS microparticles were spherical. The blend microparticles were spherical in shape with a rough surface. Average microparticle sizes were in the range of 73–80 μm. The microparticle matrices had a sponge-like morphology. Conformational changes in the SF component, from random coil to the β-sheet form, were observed in the FTIR data. The dissolution of the blend microparticles was lower than those of the plain SF and CS microparticles. Microparticle density steadily increased and porosity slightly decreased as the amount of CS in the blend increased.

Novel Pullulan–Eudragit® S100 blend microparticles for oral delivery of risedronate: Formulation, in vitro evaluation and tableting of blend microparticles

Polymer blends have been considered a promising strategy to tailor drug release. In order to achieve gastroresistance and controlled release, Pullulan, a polysaccharide, and Eudragit® S100, an enteric polymer were selected to prepare microparticles for oral delivery of risedronate, an antiresorptive drug associated with GI tract injuries. Blend microparticles were prepared by spray-drying technique at 3 Pullulan and Eudragit® S100 ratios (MP2:1, MP1:1 and MP1:2) and were characterized in terms of yield, particle size, encapsulation efficiency, morphology, moisture content, flowability and in vitro drug release profiles. Microparticles presented yields between 31 and 42%, encapsulation efficiencies close to 100%, moisture contents lower than 11%, particle size ranging from 2.9 to 4.8μm and narrow distribution. In the gastric medium, MP1:2 showed the best gastroresistance profile. In the intestinal fluid, all samples were able to prolong drug release. MP1:2 was compressed into tablets with or without polyvinylpyrrolidone. Both tableted microparticles could be obtained with acceptable average weights, drug content close to 100%, sufficient hardness and low friability. In vitro studies showed that tablets maintained the gastroresistance observed for microparticles and were also able to prolong risedronate release. In conclusion, Pullulan/Eudragit® S100 microparticles are promising alternatives for the oral delivery of risedronate in the future.

Preparation of Starch/Gelatin Blend Microparticles by a Water-in-Oil Emulsion Method for Controlled Release Drug Delivery.

Information on the preparation and properties of starch/gelatin blend microparticles with and without crosslinking for drug delivery is presented. The blend microparticles were prepared by the water-in-oil emulsion solvent diffusion method. Glutaraldehyde and methylene blue were used as the crosslinker and the water-soluble drug model, respectively. The blend microparticles were characterized by scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, and UV-Vis spectroscopy. The functional groups of the starch and gelatin blend matrices were determined from the FTIR spectra. Blend microparticles with a nearly spherical shape and internal porous structure were observed from SEM images. The average particle size of the gelatin microparticles depended on the crosslinker ratio but not on the starch/gelatin blend ratio. The in vitro drug release content significantly decreased as the crosslinker ratio increased and the starch blend ratio decreased. The results demonstrated that the starch/gelatin blend microparticles should be a useful controlled release delivery carrier for water-soluble drugs.

Drug release optimization from microparticles of poly(E-caprolactone) and hydroxypropyl methylcellulose polymeric blends: formulation and characterization

In this study, polymeric blend microparticles are prepared with tunable drug releasing behavior, imparted by using poly(e-caprolactone) (PCL) as hydrophobic and hydroxypropyl methylcellulose (HPMC) as hydrophilic biodegradable polymeric constituents. Microparticles were prepared by simple oil in water emulsion-solvent evaporation method and evaluated for their sustained release profile by using nifedipine (half-life is about 2 h) as model drug. Hydrophilic PCL is added to optimize the drug release in simulated aqueous body fluid. Polyvinyl alcohol (PVA), used as emulsifier, was found to improve shape while HPMC increased surface smoothness of microparticles. High encapsulation efficiency was achieved, controllable by HPMC concentration. In vitro dissolution studies in acidic and neutral pH showed sustained release profile for all formulations. Synthesized microparticles, provided control over hydrophobic drug release by changing the proportion of HPMC and PCL in formulation at both acidic and intestinal pH.

Preparation and characterization of novel PBAE/PLGA polymer blend microparticles for DNA vaccine delivery.

Context. Poly(beta-amino ester) (PBAE) with its pH sensitiveness and Poly(lactic-co-glycolic acid) (PLGA) with huge DNA cargo capacity in combination prove to be highly efficient as DNA delivery system. Objective. To study the effectiveness of novel synthesized PBAE polymer with PLGA blend at different ratios in DNA vaccine delivery. Methods. In the present study, multifunctional polymer blend microparticles using a combination of PLGA and novel PBAE polymers A1 (bis(3-(propionyloxy)propyl)3,3′-(propane-1,3-diyl-bis(methylazanediyl))dipropanoate) and A2 (bis(4-(propionyloxy)butyl)3,3′-(ethane-1,2-diyl-bis(isopropylazanediyl))dipropanoate) at different ratios (85 : 15, 75 : 25, and 50 : 50) were prepared by double emulsion solvent removal method. The microparticles were characterized for cytotoxicity, transfection efficiency, and DNA encapsulation efficiency. Result. It was evident from results that among the microparticles prepared with PLGA/PBAE blend the PLGA : PBAE at 85 : 15 ratio was found to be more effective combination than the microparticles prepared with PLGA alone in terms of transfection efficiency and better DNA integrity. Microparticles made of PLGA and PBAE A1 at 85 : 15 ratio, respectively, were found to be less toxic when compared with microparticles prepared with A2 polymer. Conclusion. The results encourage the use of the synthesized PBAE polymer in combination with PLGA as an effective gene delivery system.

Assessment of Immune Response to Hepatitis B Vaccine: Comparison of Novel Polycaprolactone Blend Microparticles Based Hepatitis B Vaccine and Alum Based Vaccine

Assessment of Immune Response to Hepatitis B Vaccine: Comparison of Novel Polycaprolactone Blend Microparticles Based Hepatitis B Vaccine and Alum Based Vaccine

Coated Interpenetrating Blend Microparticles of Chitosan and Guar Gum for Controlled Release of Isoniazid

This work reports on the novel development of IPN microparticles of chitosan (CS) and guar gum (GG) that are enteric coated with NaAlg and magnesium aluminum silicate (MAS) for controlled release of isoniazid. The matrices have been characterized by X-ray diffraction (XRD) to understand drug distribution, DSC for thermal stability, and Fourier transform infrared spectroscopy (FTIR) for investigating the chemical interactions of drug with the matrices. Surface morphology was investigated by scanning electron microscopy. These microparticles exhibited encapsulation efficiencies from 47 to 58%. Equilibrium swelling as well as in vitro release trends of the formulations studied in pH 1.2 and 7.4 buffer media showed the dependence of drug release on cross-linking, blend ratio of the matrix and coating, all of which affected the release time of drug from 1 to 4 h up to 50 h. The coated microparticles have reduced the burst release in gastric media to enhance in intestinal media.

Engineering polymer blend microparticles: An investigation into the influence of polymer blend distribution and interaction

The aim of this work was to understand the influence of polymer interaction and distribution on drug release from microparticles fabricated from blends of polymers. Blends of pH dependent polymer (Eudragit S, soluble above pH 7) and pH independent polymer (Eudragit RL, Eudragit RS or ethylcellulose) were incorporated into prednisolone loaded microparticles using a novel emulsion solvent evaporation method. Microparticles fabricated from blends of Eudragit S and Eudragit RL or RS did not modify drug release compared to microparticles fabricated from Eudragit S alone. This can be attributed to the high degree of miscibility of Eudragit S with Eudragit RS or Eudragit RL within the microparticles as confirmed by glass transition temperature measurements and confocal laser scanning microscopy. In contrast, microparticles prepared from blends of Eudragit S (75%) and ethylcellulose (25%) extended the release of prednisolone at pH 7.4 (compared to Eudragit S microparticles). This change in release profile was related to the immiscibility of Eudragit S and ethylcellulose as assessed by thermal analysis, and confirmed by microscopy which showed pores within the microparticle structures following dissolution of the Eudragit S domains. The ability of water insoluble polymers to extend drug release from enteric polymer microparticles is dependent on the miscibility and interaction of the polymers. This knowledge is important in the design of pH responsive microparticles capable of extending drug release in the gastrointestinal tract.

PLGA:poloxamer blend micro- and nanoparticles as controlled release systems for synthetic proangiogenic factors

Tissue engineering is one of the most promising research areas in bioregenerative medicine. However, the restoration of biological functionalities by implanting bioartificially engineered tissues is still highly limited because of their lack of vascular networks. The use of proangiogenic molecules delivered from a controlled release device is a promising strategy to induce tissue vascularization. Indeed, the controlled release system can enhance the therapeutic effect in vivo of many short half-life drugs, while circumventing the need for repeated administrations. In this work, PLGA:poloxamer blend based micro- and nanoparticles have been developed for the sustained delivery of a recently developed synthetic proangiogenic compound: SHA-2-22. Drug-loaded PLGA:poloxamer blend microparticles were prepared by an oil-in-oil solvent extraction/evaporation technique. Drug-loaded PLGA:poloxamer nanoparticles were prepared by a modified solvent diffusion technique. These drug carriers were characterized with regard to their physicochemical properties, morphology, drug encapsulation efficiency and release kinetics in vitro. The results show that by adjusting the formulation conditions, it is possible to obtain PLGA:poloxamer micro- and nanoparticles with very high drug loadings, and with the capacity to release the active compound in a controlled way for up to one month. In vitro cell assays performed in an endothelial cell model confirmed the bioactivity of SHA-22-2 encapsulated in PLGA:poloxamer microparticles.

Gastroresistant microparticles containing sodium alendronate prevent the bone loss in ovariectomized rats

Sodium alendronate, an antiresorptive drug, primarily used in the treatment of osteoporosis was encapsulated in blended microparticles composed of Eudragit ® S100 and Methocel ® K15M. The micropowder obtained by spray-drying technique was characterized in terms of its morphology, particle size, encapsulation efficiency and in vitro drug release. In vivo studies were carried out in order to evaluate the pharmacodynamic effect and the ulcerogenic activity of sodium alendronate-loaded microparticles after oral administration in rats. Drug encapsulation efficiency was close to 80% and particle mean diameter of 13.8 μm. SEM analysis showed spherical collapsed shape particles with smooth surface. At pH 1.2, in vitro experiments showed that <10% of the drug was released from the microparticles. At pH 6.8, the microparticles were able to prolong the sodium alendronate release for 12 h. In vivo experiments carried out in ovariectomized rats showed bone mineral density significantly higher for the sodium alendronate-loaded microparticles than for the negative control groups. Furthermore, the microencapsulation of the drug showed a significant reduction in the ulcerative lesion index. In conclusion, the blended microparticles are excellent oral carriers for sodium alendronate since they were able to maintain the drug antiresorptive effect and to reduce the gastrointestinal drug toxicity.

Microencapsulation of sodium alendronate reduces drug mucosal damage in rats

Sodium alendronate is an effective treatment for osteoporosis, but its oral administration is associated with adverse gastrointestinal effects. The aim of this work was to evaluate gastroresistant sodium alendronate-loaded microparticles prepared by spray-drying using Eudragit® S100 or a blend of Eudragit® S100/Methocel® E4M. Both formulations presented high encapsulation efficiencies, mean diameters below 17 μm, and similar collapsed shape. Dissolution experiments showed good gastro-resistance for the microparticles at pH 1.2. At pH 6.8, the blended microparticles retarded the drug release. In vivo studies showed that the formulations were able to protect the rat stomachs against ulcer formation by sodium alendronate. In conclusion, the microparticles seems to be promising oral carriers for sodium alendronate.