Structure and mechanical properties of polylactide copolymer microspheres and capsules

Polylactide homopolymers, polylactide and poly(ethylene oxide) diblock and triblock copolymers are used to prepare spherical microparticles by using the single oil-in-water emulsion and solvent evaporation technique. We are able to create both bulk and hollow microspheres by altering the conditions of preparation. The experiments are carried out at two fixed temperatures of 15 and 22 °C. We show, from scanning electron microscopy data, that the microspheres produced from the homopolymers are bulk and homogeneous at both temperatures whereas they are hollow when the triblock copolymers are used. The diblock copolymers yield bulk microspheres at 15 °C and microcapsules at 22 °C. Compression experiments emphasize once more the inner morphology of the spheres. As it is expected, bulk microspheres have higher Young’s modulus than the microcapsules. Nevertheless, comparative compression analysis of both morphologies shows that the microcapsules retain relatively high compressive moduli. These results have implications for the design of rigid and biodegradable microcapsules.     

Spontaneous formation of polylactide stereocomplex microspheres containing metal ions

Linear poly(l ‐lactides) (PLLAs ) and poly(d ‐lactides) (PDLAs ) with M _n in the range 2000 ? 4300 containing a different number and placement of carboxyl groups were obtained via cationic ring‐opening polymerization and post‐polymerization functionalization. PLA stereoisomers (PLLA ‐(COOH )_x and PDLA ‐(COOH )_x , where x = 1 ? 3) were used for the investigation of stereocomplexation in solution performed in the presence of metal cations such as Ca²⁺, Mg²⁺, Zn²⁺, Fe³⁺. Spherical microparticles with a diameter in the range 0.7 ? 3.0 µm were obtained in all cases which was confirmed on the basis of scanning electron microscopy (SEM ) analysis. The microsphere size and homogeneity were analyzed depending on the stereocomplexation conditions and the molecular weight as well as the number of carboxyl end groups in the PLLA and PDLA used for stereocomplexation. The PLA microspheres obtained were analyzed by Fourier transform IR spectroscopy, wide angle X‐ray spectroscopy and energy‐dispersive X‐ray spectroscopy methods which confirmed the presence of metal cations inside. The application of regular microspheres with metal ions as drug delivery systems is considered. © 2016 Society of Chemical Industry     

Protein microspheres for pulmonary drug delivery

A new supercritical fluid (SCF) technique was developed for the preparation of microspheres for pulmonary drug delivery (PDD). This technique, based on the anti-solvent process, has incorporated advanced engineering design features to enable improved control of the particle formation process. Human recombinant insulin (HRI) was used as a model compound to evaluate the efficiency of this SCF process. An aqueous solution of HRI with a co-solvent was sprayed into high pressure carbon dioxide that extracted the solvent and water, leading to a dry fine powder with good particle size distribution and near ideal morphology for pulmonary drug delivery.     

Development of biodegradable polymeric nanoparticles for encapsulation,delivery, and improved antifungal performance of natamycin

The aim of this study was to evaluate biodegradable poly(lactide‐co‐glycolide) nanoparticles as potential nano‐delivery systems for the food antifungal compound natamycin. Natamycin‐loaded nanoparticles were prepared at various ratios polymer/antifungal by the nanoprecipitation technique, resulting in nano‐size particles (80–120 nm) with a narrow distribution and a spherical morphology. Complexation of natamycin with PLGA and active participation to the nanoparticle formation were evidenced by a mean diameter reduction of 10–30 nm, although encapsulation levels remained low due to the zwitterionic and partially hydrophilic nature of natamycin. Physical state analyses highlighted the presence of natamycin in an amorphous or molecularly dispersed state within the polymeric matrix. This translates into high availability of free antifungal molecules reflected in burst release and fast in vitro release kinetics rates as well as enhanced antifungal performance against the model food yeast Saccharomyces cerevisiae, offering a potential benefit for antifungal protection compared with the commercially available natamycin products. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 43736.     

In vitro degradation of polylactide and poly(lactide-co-glycolide) microspheres

Polyactide (PLA) and poly(lactide-co-glycolide) (PLGA) were prepared by bulk ring-opening polymerization of lactide or lactide/glycolide using stannous octoate as initiator. PLA and PLGA microspheres with an average diameter of 65–100 μm were prepared by a solvent evaporation process. An in vitro degradation test of different molecular weight PLA and of different composition PLGA were carried out in pH 7.4 buffer solution at 37°C in the form of microspheres. Quantitatively, the degree of degradation was monitored by gel permeation chromatography (GPC), by measurement of mass loss and determination of lactic/glycolic acid in degradation medium, and qualitatively, by observing the morphological changes of microspheres with a scanning electron microscope (SEM). The decrease in weight average molecular weight (M _w) for PLA with higher molecular weight is faster at the first degradation stage; afterward, the tendency of M _w to decrease for PLA with different molecular weight is almost the same. PLGA degrades much faster than does PLA, and the degradation rate is significantly enhanced with the increase of glycolic acid (GA) content in copolymers.     

Microfluidics for producing polylactide nanoparticles and microparticles and their drug delivery application

This review presents use of the microfluidics technique for the preparation of polylactide (PLA) based particles for developing novel drug delivery systems. Droplet‐based microfluidics allow uniform single, double and higher order emulsions to be generated that yield highly uniform microspheres, microcapsules and polymersomes. Typically, the building blocks of these complex microparticle systems are PLA macromolecules, their copolymers with different comonomers and recently stereocomplexes composed of an equimolar mixture of poly(l ‐lactide) and poly(d ‐lactide). In addition, the technique offers several advantages over conventional emulsion methods and the highly uniform droplets obtained allow for encapsulation of small drug molecules in polymer network meshes or within their hollow interior. The novel approach in this area is to use the microfluidics technique to produce nanoparticles in the microfluidics channel by micromixing/nanoprecipitation in glass capillary devices. Therefore, this review is divided into three main sections in which we discuss the formation of microspheres from single emulsion droplets, microcapsules and polymersomes from higher order emulsion droplets, and nanoparticles from nanosuspensions in a microfluidic channel. Finally, we compare the drug release from these different particles, focusing mainly on those formed from sensitive or supramolecular networks. © 2018 Society of Chemical Industry     

Development of tunable biodegradable polyhydroxyalkanoates microspheres for controlled delivery of tetracycline for treating periodontal disease

This article was aimed at preparation and characterization of drug delivery carriers made from biodegradable polyhydroxyalkanoates (PHAs) for slow release of tetracycline (TC) for periodontal treatment. Four PHA variants; polyhydroxybutyrate (PHB), poly(hydroxybutyrate‐co‐hydroxyvalerate) with 5, 12, and 50% hydroxyvalerate were used to formulate TC‐loaded PHA microspheres by double emulsion‐solvent evaporation method. We also compared the effect of different molecular weight (M_w) of polyvinyl alcohol (PVA) acting as surface stabilizer on particle size, drug loading, encapsulation efficiency, and drug release profile. The TC‐loaded PHA microspheres exhibited microscale and nanoscale spherical morphology under scanning electron microscopy. Among formulations, TC‐loaded PHB:low M_w PVA demonstrated the highest TC loading with slow release behavior. Our results showed that the release rate from PHA microspheres was influenced by both the type of PHA and M_w of PVA stabilizer. Lastly, TC‐loaded PHB microspheres showed efficient killing activity against periodontitis‐causing bacteria, suggesting its potential application for treating periodontal disease. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 44128.     

Silk fibroin microspheres prepared by the water-in-oil emulsion solvent diffusion method for protein delivery

Silk fibroin (SF) microspheres were prepared by the simple water-in-oil emulsion solvent diffusion method without any surfactants. Aqueous SF solution and dichloromethane were used as water and oil phases, respectively. Influence of water: oil phase ratios on SF microsphere characteristics was investigated. From FTIR spectra, the resulting SF microspheres showed predominantly random coil SF conformation. SF microspheres observed from SEM images were spherical with deflated surfaces in some cases. Particle sizes of the SF microspheres were in the range 45–92 μm. Finally, bovine serum albumin (BSA) was used as a model protein for entrapment within the SF microspheres. The BSA-loaded SF microspheres were larger than unloaded SF microspheres. In vitro release tests indicate that BSA release from the SF microspheres was influenced by BSA content.     

Novel strategy for encapsulation and targeted delivery of poorly water-soluble active substances

Carriers for targeted delivery and controlled release of poorly water-soluble active substances (PWSAS) are facing three challenges: (a) the encapsulation issues, (b) limitations of PWSAS water solubility, and (c) burst drug release which can be pharmacologically dangerous and economically inefficient. The present study brings a novel strategy for encapsulation and controlled release of PWSAS—caffeine in concentrations which are higher than its maximal water solubility without the possibility of burst effect. The modification of hydrophilic carrier based on poly(methacylic acid) was done using casein and liposomes. To further increase the maximal caffeine loading inside the carrier nicotinamide was used. The release study of the encapsulated PWSAS was elaborated with respect to morphology of the carriers and interactions that could be established between its structural components. The carriers swelling and the release of caffeine and nicotinamide were also investigated depending on caffeine concentration, the presence of different liposomal formulations and the volume ratio of liposomal formulation, in three media with different pH simulating the path of the carrier through the human gastrointestinal tract. The synthesized carriers are promising candidates for encapsulation of PWSAS in concentrations which are higher than its maximal water solubility and for the targeted delivery of those dosages.     

Spray-dried nanoparticle-loaded pectin microspheres for dexamethasone nasal delivery

Abstract

In this study, we present the development of an innovative dry powder dexamethasone (Dex) nasal delivery system comprising Dex-loaded lipid/alginate nanoparticles incorporated within pectin microspheres (Dex/NPs-loaded pectin microspheres; DNM). DNM microspheres were characterized by the mean diameter of 2.76?±?0.10?µm, zeta-potential of –36.2?±?1.1?mV, and drug loading of 3.3?±?0.3%. The morphology study revealed irregular microsphere surface forming external voids. In contact with simulated nasal fluid, DNM microspheres demonstrated desirable property of moderate swelling and ensured stronger mucoadhesion compared with conventional Dex-loaded pectin microspheres. The strategy of Dex incorporation within the lipid/alginate NPs resulted in prolonged Dex release in relation to Dex being directly entrapped within the conventional pectin microspheres. DNM microspheres showed excellent biocompatibility and rendered Dex permeation across the selected epithelial cell model similar to that of Dex solution. In conclusion, balanced biopharmaceutical properties of the proposed nasal Dex delivery system provides the potential for prolonged contact time with nasal mucosa, prolonged therapeutic effect, and improved patient compliance.     

Preparation of chitosan nanoparticles for encapsulation and release of protein

Chitosan nanoparticles were prepared by ionic cross-linking with tripolyphosphate (TPP). The major effect on encapsulation and release of protein in chitosan-TPP nanoparticles was investigated in order to control the loading and release efficiency. A set of the same molecular weight (MW) proteins with different pI and a set of the same pI proteins with different MW were studied. The influence of protein concentration, pH of solution, and the activity of released protein were examined. It was found that the encapsulation efficiency (EE) of a set of the different MW protein decreased with increasing of MW of protein and protein concentration. The protein with having pI higher than pH of solution was attracted to the positively charged chitosan, resulting in increasing of EE. The release of protein from the nanoparticles showed that the protein release decreased with increasing of chitosan concentration, high MW protein, low pH, and less swelling of the particle. The released protein in chitosan-TPP matrix was still active in the buffer solution.     

Fabrication and characterization of bioactive calcium silicate microspheres for drug delivery

The calcium silicate (CaSiO₃, CS) microspheres with diameter of 75–100 μm were fabricated by a spray-drying method. A new bone-like apatite layer fully covered the surface of the fabricated CS microspheres after soaking in simulated body fluid (SBF), suggesting the excellent activity of the material in inducing apatite deposition. The ionic extracts of CS microspheres promoted the proliferation of human osteoblast-like cells (MC3T3-E1). In addition, the porous structures of the CS microspheres resulted in favorable drug loading and sustained release property. Our study indicates that the fabricated multifunctional CS microspheres are a promising drug delivery system as an injectable bioactive filling material for bone-regeneration.     

电子封装用聚氨酯灌封胶的研制

以球形Al_2O_3(氧化铝)为导热填料、改性PAPI 9258(多苯基多亚甲基多异氰酸酯)为固化剂,并引入自制的高效液体阻燃剂,成功制备了一种兼具导热、阻燃和高流动性的PU(聚氨酯)灌封胶。研究结果表明:当m(树脂组分)∶m(固化剂)=6∶1、树脂组分中w(球形Al_2O_3)=67%和w(液体阻燃剂)=13%时,PU灌封胶的综合性能相对最好,其导热系数为0.815 W/(m·K)、阻燃等级为UL-94 V0级、常温拉伸剪切强度为11.79 MPa且流动性良好,完全满足多功能灌封胶的使用要求。     

pH-responsive gelatin microspheres for oral delivery of anticancer drug methotrexate

Multiple unit delivery dosage forms of biodegradable gelatin microspheres containing the anticancer drug methotrexate (GMM) of various mean particle sizes (1–5, 5–10, and 15–20 μm) were prepared by the polymer dispersion technique and were crosslinked with glutaraldehyde. The GMM were coated with biodegradable natural polymers, namely alginate (AGMM) and chitosan (CGMM), which differ in their pH sensitivity, to obtain two different types of pH dependent delivery systems for oral delivery of methotrexate (MTX). The in vitro release profiles of MTX from AGMM and CGMM were determined in simulated gastric medium, intestinal medium, and in media simulating gastrointestinal tract conditions. The effect of the concentration of coating polymer and particle size on the release rate of MTX from both AGMM and CGMM were also studied. Both AGMM and CGMM provided controlled release of MTX following a zero-order release pattern in gastric and intestinal fluids for prolonged periods of time. The release rate of MTX decreased with an increase in concentration of the coating polymer as well as an increase in particle size of the microspheres. Both AGMM and CGMM showed good potential as pH dependent multiple unit delivery systems for the controlled release of MTX in oral administration. © 1995 John Wiley & Sons, Inc.     

Investigation on preparation and protein release of biodegradable polymer microspheres as drug‐delivery system

Among the different approaches to achieve protein delivery, the use of polymers, especially biodegraded, holds great promise. This work aimed to study the preparation and protein release of a novel drug‐delivery system based on human serum albumin (HSA) encapsulated into biodegradable polymer microspheres. The microspheres containing HSA were elaborated by the solvent‐extraction method based on the formation of multiple w/o/w emulsion. The encapsulation efficiency (E.E.) of HSA was determined by the CBB method. Alginate/alginate and calcium chloride was added into an internal aqueous phase to investigate the protein loading efficiency, protein stability, and in vitro release profiles. Microspheres were characterized in terms of their morphology, size distribution, loading efficiency, and in vitro protein release. SDS–PAGE results showed that HSA kept its structural integrity during the encapsulation and release procedure. In vitro studies indicated that the microspheres with alginate added in the internal aqueous phase had a smaller extent of burst release. In conclusion, the work presents a new approach for macromolecular drugs (such as protein drugs, vaccines, and peptide drugs) delivery. © 2002 John Wiley & Sons, Inc. J Appl Polym Sci 84: 778–784, 2002; DOI 10.1002/app.10327     

Whey protein aggregates-alginate composite gel for astaxanthin-chia oil encapsulation

Chia oil (rich in omega-3 fatty acids) and astaxanthin are associated with various benefits for human health. However, their low solubility and poor stability reduce their direct use as bioactive compounds. Its encapsulation within the appropriate material can be a solution in this case. This work evaluated the effect of whey protein aggregates (WPA) on the storage stability of chia oil-astaxanthin blends encapsulated in alginate gel beads. Bead characteristics and the stability of encapsulated bioactive compounds stored at 25°C for 30 days were evaluated. High values of encapsulation efficiency (>85%) were observed in the cases studied. The addition of WPA affected some characteristics of the beads and improved the stability of the bioactive compounds compared to pure alginate beads. After 30 days of storage, higher preservation of astaxanthin and lower content of lipid oxidation products were observed in beads with WPA compared to alginate beads.     

Synthesis of collagen‐modified polylactide and its application in drug delivery

In this article, collagen modified polylactide (CPLA) was synthesized by means of graft modification, and its structure was confirmed by FTIR and FITC‐labeled fluorescence spectra. Subsequently, the performance of CPLA was characterized with hydrophilicity test and degradability test. After that, the aspirin sustained release microspheres of the synthetic copolymers were prepared via the emulsion‐solvent evaporation technique, followed with its measurements of morphology, size, and encapsulation efficiency. Finally, the controlled release properties of the obtained microspheres were investigated. The results showed that the aspirin sustained release microspheres exhibited well‐defined morphology with smooth spherical surface, with average size of 3.990 μm and encapsulation efficiency of 51.83%. Furthermore, compared with aspirin‐loaded PLA microspheres, at the initial 32 h, the drug release was faster for aspirin‐loaded CPLA microspheres favored by its increased hydrophilicity, and then the drug release was slower than that of PLA microspheres because the ? NH₂ group on the introduced collagen inhibited acidic autocatalytic degradation. The results suggested that CPLA showed a great potential as particles for drug delivery. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

Biocompatibility and characteristics of theophylline/carboxymethyl chitosan microspheres for pulmonary drug delivery

The main aim was to evaluate the biocompatibility of theophylline/carboxymethyl chitosan/β‐cyclodextrin microspheres made by spray drying for pulmonary delivery. Haemolysis tests and cell culture experiments were used to determine blood and cell biocompatibility, and in vivo implantation experiments were used to examine tissue biocompatibility. The theophylline/carboxymethyl chitosan/β‐cyclodextrin microspheres were spherical in shape with a smooth or wrinkled surface, and showed no haemolysis activity. The cytotoxicity was dependent on concentration and showed no toxicity at low concentration. The results of implantation indicated that the inflammatory reaction gradually lessened and disappeared and had no significant difference from that of an operative suture. Therefore, theophylline/carboxymethyl chitosan/β‐cyclodextrin microspheres possess good biocompatibility and can be used as a promising carrier for pulmonary drug delivery. © 2013 Society of Chemical Industry     

Optimization of protein encapsulation in PLGA nanoparticles

Influences of process parameters were investigated on the efficiency of encapsulation of bovine serum albumin (BSA) in poly(dl-lactic-co-glycolic acid) (PLGA) nanoparticles produced by w₁/o/w₂ (water-in-oil-in-water) double emulsion-solvent evaporation method. According to a 5-factorial 3-level Box-Behnken type experimental design aqueous solution of BSA was emulsified in an immiscible organic phase composed of dichloromethane and various quantities of dissolved PLGA to get water-in-oil (w₁/o) emulsion. This latter was then dispersed in a second aqueous phase (w₂) containing poly-vinyl-alcohol (PVA) surfactant as an emulsifier/stabilising agent. PLGA nanoparticles with encapsulated BSA were obtained by evaporating the dichloromethane from the w₁/o droplets. Encapsulation efficiency was determined as the weight ratio of BSA remained in the PLGA nanoparticles relative to the total weight of BSA used in the process. By statistical evaluation of the experimental results an equation was proposed to predict the encapsulation efficiency as a function of five process variables. Two optimization procedures were carried out to increase the efficiency of encapsulation, with and without constraints referring to the required mean particle size. Correlation was found between the latter and the achievable maximal encapsulation efficiency under optimal process conditions.