Biodegradable hollow microfibres to produce bioactive scaffolds

Biodegradable hollow microfibres containing particles loaded with specific active agents can be potentially employed to produce a special kind of substrate for tissue engineering, able to function as a scaffold and at the same time to act as a drug‐releasing system. Biodegradable hollow microfibres based on poly(lactic acid) were produced by a dry–wet spinning procedure. Drug‐loaded microparticles were prepared by a simple oil‐in‐water emulsion and entrapped inside the fibres. The morphology of both fibres and particles was investigated by scanning electron microscopy. The mechanical and thermal properties of the fibres were investigated by tensile tests and differential scanning calorimetry. In vitro tests were performed to evaluate the release of the drug from the fibres loaded with the particles Copyright © 2004 Society of Chemical Industry     

Preparation and release characteristics of dexamethasone acetate loaded organochlorine‐free poly(lactide‐co‐glycolide) nanoparticles

Dexamethasone‐loaded poly(lactide‐co‐glycolide) (PLGA) devices are commonly used as model systems for controlled release. In this study, PLGA nanoparticles containing dexamethasone acetate were prepared by a nanoprecipitation technique in the absence of organochlorine solvents and were characterized by their mean size, ζ potential, scanning electron microscopy, and differential scanning calorimetry to develop a controlled release system. The analytical method for the quantification of dexamethasone acetate by high‐performance liquid chromatography was validated. The results show that it was possible to prepare particles at a nanometric size because the average diameter of the drug‐loaded PLGA particles was 540 ± 4 nm with a polydispersity index of 0.07 ± 0.01 and a ζ potential of ?2.5 ± 0.3 mV. These values remained stable for at least 7 months. The drug encapsulation efficiency was 48%. In vitro tests showed that about 25% of the drug was released in 48 h. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 41199.     

Exploring poly(vinyl alcohol) hydrogels containing drug–cyclodextrin complexes as controlled drug delivery systems

Poly(vinyl alcohol) (PVA) hydrogels containing drug–β‐cyclodextrin inclusion complexes (ICs) were synthesized with glutaraldehyde (GA) as a crosslinker. The role of cyclodextrin (CD), the effect of the nature of drug, and the degree of crosslinking on the drug‐release process were investigated. The probable mechanism of drug release was also explored. Controlled release of the drug was achieved from the hydrogels containing the ICs. The nature of the drug, in terms of its binding efficacy with CD, played an important role. The effect of the degree of crosslinking on the release pattern was strikingly different from that in the hydrogels containing free drug and those with ICs. The role of CD in the drug‐release process was not only due to its inclusion ability but also its effect on the polymer relaxation. GA, apart from crosslinking PVA, probably interacted with the cyclodextrins and, thereby, influenced the matrix structure and the drug‐release kinetics. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40318.     

Pilocarpine‐loaded poly(DL‐lactic‐co‐glycolic acid) nanoparticles as potential candidates for controlled drug delivery with enhanced ocular pharmacological response

The poor corneal residence time of pilocarpine, an alkaloid extracted from the leaves of the Jaborandi plant, limits its ocular application. The aim of this study was to develop, characterize, and evaluate the potential of pilocarpine entrapped by poly(DL ‐lactic‐co‐glycolic acid) (PLGA) nanoparticle carriers for ocular drug delivery. Pilocarpine‐loaded nanoparticles were prepared with a double‐emulsion (water in oil in water) method and characterized with transmission electron microscopy and X‐ray diffraction analysis. The nanoparticles exhibited an average size of 82.7 nm with an encapsulation efficiency of 57%. Stability studies showed the absence of agglomeration and constancy in the amount of drug entrapped; this indicated the solidity of these particles for long‐term use. The in vitro release studies conducted in simulated tear fluid showed the sustained release of pilocarpine. In vivo evaluation of the nanoparticles was done in a rabbit model with a miosis assay and compared to an equal dose of commercially available eye drops of pilocarpine (Pilocar drops). The in vivo miosis studies showed that the duration of miotic response increased by 40% for the nanoparticles and produced an almost 68% increase in total miotic response when compared to the eye drops. In conclusion, this study clearly demonstrated the potential of pilocarpine‐loaded PLGA nanoparticles for multiplying the therapeutic effect of ophthalmic drug delivery with enhanced bioavailability and pharmacological response. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

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     

Hydroxybisphosphonate‐containing polymeric drug‐delivery systems designed for targeting into bone tissue

The preparation and characterization of a novel polymeric drug‐delivery system designed for bone targeting of antineoplastics is described. The system was based on biocompatible poly[N‐(2‐hydroxypropyl)methacrylamide] carrier containing hydroxybisphosphonate targeting moieties and the model radiotherapeutics ¹²⁵I or ¹¹¹In or the anticancer drug doxorubicin. The in vitro binding studies with hydroxyapatite as a bone model proved that the system was efficiently adsorbed on this mineral. The systems contained model drugs bound by stable (amide), hydrolytically cleavable (hydrazone) or enzymatically cleavable (Gly‐Phe‐Leu‐Gly tetrapeptide) spacers. It was proven in vitro that, in the case of cleavable spacers, the drug could be released from the polymer carrier at a rate depending on the pH or enzymatic stimulus. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci: 3192–3201, 2006     

Novel thermosensitive hydrogel composites based on poly(d,l‐lactide‐co‐glycolide) nanoparticles embedded in poly(n‐isopropyl acrylamide) with sustained drug‐release behavior

To reach sustained drug release, a new composite drug‐delivery system consisting of poly(d,l ‐lactide‐co‐glycolide) (PLGA) nanoparticles (NPs) embedded in thermosensitive poly(N‐isopropyl acrylamide) (PNIPAAm) hydrogels was developed. The PNIPAAm hydrogels were synthesized by free‐radical polymerization and were crosslinked with poly(ethylene glycol) diacrylate, and the PLGA NPs were prepared by a water‐in‐oil‐in‐water double‐emulsion solvent‐evaporation method. The release behavior of the composite hydrogels loaded with albumin–fluorescein isothiocyanate conjugate was studied and compared with that of the drug‐loaded neat hydrogel and PLGA NPs. The results indicate that we could best control the release rate of the drug by loading it to the PLGA NPs and then embedding the whole system in the PNIPAAm hydrogels. The developed composite hydrogel systems showed near zero‐order drug‐release kinetics along with a reduction or omission of initial burst release. The differential scanning calorimetry results reveal that the lower critical solution temperature of the developed composite systems remained almost unchanged (<1°C increase only). Such a characteristic indicated that the thermosensitivity of the PNIPAAm hydrogel was not distinctively affected by the addition of PLGA NPs. In conclusion, an approach was demonstrated for the successful preparation of a new hybrid hydrogel system having improved drug‐release behavior with retained thermosensitivity. The developed systems have enormous potential for many biotechnological applications. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40625.     

Degradation and drug‐release studies of a poly(glycolide‐co‐trimethylene carbonate) copolymer (Maxon)

Poly(glycolide‐co‐trimethylene carbonate) is available commercially as a monofilament suture known as Maxon. The literature has shown that Maxon sutures possess a slow degradation rate of about 7 months and exhibit relatively high mechanical strength in comparison with other absorbable sutures. However, very few articles are available on the degradation of unoriented Maxon. This study was designed to explore the chemical and physical aspects of the degradation of unoriented Maxon and its potential as a drug‐release device. Several analytical techniques were used, including mass measurements, simultaneous small‐angle X‐ray scattering and wide‐angle X‐ray scattering, and thermoporometry. Magnetic resonance imaging and drug‐release measurements were carried out with UV spectroscopy. The results suggest that unoriented suture‐based Maxon undergoes multiple stages of hydrolytic degradation, which involve hydration, and active and postactive periods. The drug‐release mechanism is controlled by diffusion in the early degradation stages and polymer erosion in the later stages of release. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 95: 475–486, 2005     

In vitro degradation and drug‐release behavior of electrospun,fibrous webs of poly(lactic‐co‐glycolic acid)

Ultrafine fibrous webs of poly(lactide‐co‐glycolic acid) (PLGA) containing the bactericidal antibiotic drug rifampin were prepared by electrospinning, and their properties were investigated for wound‐dressing applications. Because PLGA is a biodegradable and biocompatible polymer, it is one of the best materials for the preparation of wound‐dressing substrates. Through this investigation of PLGA/rifampin electrospun webs, we found that the in vitro degradation reached approximately 60% in 10 days, and the drug release from the webs showed a fast and constant profile suitable for wound‐dressing applications. Also, we observed that both the web‐degradation rate and the drug‐release rate increased as the drug concentration in the PLGA/rifampin electrospun webs and the content level of glycolide units in the PLGA polymer matrix increased. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

Preparation and in vitro drug‐release behavior of 5‐fluorouracil‐loaded poly(hydroxybutyrate‐co‐hydroxyhexanoate) nanoparticles and microparticles

Poly(3‐hydroxybutyrate‐co‐3‐hydroxyhexanoate) (PHBHHx) copolymeric microparticles (MPs) and nanoparticles (NPs) were prepared by the double‐emulsion solvent‐evaporation technique. 5‐Fluorouracil (5‐Fu), an anticancer drug, was entrapped in PHBHHx NPs and MPs. A variety of parameters, including the species and concentration of different surfactants, power and time of ultrasonication for particle dispersion, and organic/aqueous solution ratio, that affected the production of the 5‐Fu‐loaded PHBHHx NP and MP particles and the release of 5‐Fu were studied. The results show that the prepared NPs and MPs were spherical in shape and about 160 nm and 3 μm in size, respectively, when cetyltrimethyl ammonium bromide was used as the emulsifier. The drug‐loading content (DLC) varied from 3.53 to 8.03% for 5‐Fu‐loaded NPs and from 4.83 to 18.87% for 5‐Fu‐loaded MPs and depended on the different initial feeding amounts of 5‐Fu. The encapsulation efficiency decreased with increasing DLC. The in vitro drug‐release characteristics appeared to have two phases with an initial burst effect occurring within the first 8 h; this was more obvious for the particles with low DLCs. The NPs with high DLC (8.03%) had the slowest release rate, 49.6% of 5‐Fu within 24 h. Therefore, PHBHHx copolymeric NPs and MPs can possibly be applied as drug‐delivery carrier materials in the future. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Biodegradable starch particles for controlled release applications: Swelling and leaching mechanisms

Starch-extruded particles have only found infrequent use as delivery systems for active ingredients. We have previously shown that these particles are attractive for releasing hydrophobic compounds in water media. Here, we cover a range of amylose–amylopectin ratios and evaluate the presence of the thyme essential oil (TEO) as active compound to understand the dominant release mechanism in relation to the physicochemical properties of the starch matrices. Starch blends with high amylopectin content (1.8 and 15% amylose) could not be shaped into regular particles. For amylose contents higher than 28%, the equilibrium degree of swelling in water decreased with increasing amylose contents, from nearly 300% for an amylose content of 28–90% at an amylose content of 70%. For both lowest amylose contents, 1.8 and 15%, leaching of solids and disintegration of the particles resulted in a low apparent degree of swelling. The presence of TEO reduces the degree of swelling of the gelatinized starch matrix. This is explained by the formation of thymol–amylose complexes, which is confirmed by Fourier transform infrared spectroscopy analysis and X-ray diffraction.     

Preparation and drug‐release behavior of minocycline‐loaded poly[hydroxyethyl methacrylate‐co‐poly(ethylene glycol)–methacrylate] films

In this work, biocompatible hydrogel matrices for wound‐dressing materials and controlled drug‐release systems were prepared from poly[hydroxyethyl methacrylate‐co‐poly(ethylene glycol)–methacrylate] [p(HEMA‐co‐PEG–MA] films via UV‐initiated photopolymerization. The characterization of the hydrogels was conducted with swelling experiments, Fourier transform infrared spectroscopy, scanning electron microscopy, thermogravimetric analysis (differential scanning calorimetry), and contact‐angle studies. The water absorbency of the hydrogel films significantly changed with the change of the medium pH from 4.0 to 7.4. The thermal stability of the copolymer was lowered by an increase in the ratio of poly(ethylene glycol) (PEG) to methacrylate (MA) in the film structure. Contact‐angle measurements on the surface of the p(HEMA‐co‐PEG–MA) films demonstrated that the copolymer gave rise to a significant hydrophilic surface in comparison with the homopolymer of 2‐hydroxyethyl methacrylate (HEMA). The blood protein adsorption was significantly reduced on the surface of the copolymer hydrogels in comparison with the control homopolymer of HEMA. Model antibiotic (i.e., minocycline) release experiments were performed in physiological buffer saline solutions with a continuous flow release system. The amount of minocycline release was shown to be dependent on the HEMA/PEG–MA ratio. The hydrogels have good antifouling properties and therefore are suitable candidates for wound dressing and other tissue engineering applications. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Self‐aggregated nanoparticles of N‐dodecyl,N′‐glycidyl(chitosan) as pH‐responsive drug delivery systems for quercetin

In this study, pH‐responsive amphiphilic chitosan (CS) nanoparticles were used to encapsulate quercetin (QCT) for sustained release in cancer therapy. The novel CS derivatives were obtained by synthesis with 2,3‐epoxy‐1‐propanol, also known as glycidol, followed by acylation with dodecyl aldehyde. Characterization was performed by spectroscopic, viscosimetric, and size‐determination methods. Critical aggregation concentration, morphology, entrapment efficiency, drug release profile, cytotoxicity, and hemocompatibility studies were also carried out. The average size distribution of the self‐assembling nanoparticles measured by dynamic light scattering ranged from 140 to 300 nm. In vitro QCT release and Korsmeyer–Peppas model indicated that pH had a major role in drug release. Cytotoxicity assessments indicated that the nanoparticles were non‐cytotoxic. 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay further revealed that QCT‐loaded nanoparticles could inhibit MCF‐7 cell growth. In vitro erythrocyte‐induced hemolysis indicated the good hemocompatibility of the nanoparticles. These results suggest that the synthesized copolymers might be potential carriers for hydrophobic drugs in cancer therapy. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 45678.     

Dual‐stimuli‐responsive polymer‐coated mesoporous silica nanoparticles used for controlled drug delivery

In this article, a temperature‐ and pH‐responsive delivery system based on block‐copolymer‐capped mesoporous silica nanoparticles (MSNs) is presented. A poly[2‐(diethylamino)ethyl methacrylate)] (PDEAEMA)‐b‐poly(N‐isopropyl acrylamide) (PNIPAM) shell on MSNs was obtained through the surface‐initiated atom transfer radical polymerization. The block copolymer PDEAEMA‐b‐PNIPAM showed both temperature‐ and pH‐responsive properties. The release of the loaded model molecules from PDEAEMA‐b‐PNIPAM‐coated MSNs could be controlled by changes in the temperature or pH value of the medium. The as‐desired drug‐delivery carrier may be applied to biological systems in the future. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42395.     

Multifunctional ternary drug‐loaded electrospun scaffolds

Multifunctional electrospun scaffolds were prepared from two polylactide (PLA) grades having slightly different d ‐lactide content (4.2 wt % and 2.0 wt %). Triclosan (TCS), ketoprofen (KTP), and p‐coumaric acid (CUM) were selected as bactericide, anti‐inflammatory, and antioxidant agents, respectively. Single, binary, and ternary drug‐loaded microfibers having a unimodal diameter distribution could be prepared using a common chloroform:acetone:dimethylsulfoxide mixture and similar operational parameters (i.e., voltage, flow rate, and tip–collector distance). FTIR spectra were sensitive to the low amount of drugs loaded and even showed slight differences in PLA conformation. DSC heating scans clearly demonstrated the ability of electrospinning to induce molecular orientation of PLA and also the nucleation effect of incorporated drugs to induce crystallization. Thus, crystallinity of binary drug‐loaded scaffolds was significantly higher than observed for unloaded samples. Release behavior of the three drugs from loaded scaffolds and PLA matrices in PBS:ethanol medium was evaluated. A rapid release was always detected, together with partial drug retention which was higher when the more stereoregular PLA matrix was employed. A strong bactericidal effect was found when scaffolds were loaded with 3 wt/vol % of TCS, but incorporation of a small percentage of KTP (i.e., 1 wt/vol %) had a bacteriostatic effect even in the absence of TCS. The inherent cytotoxicity of TCS could be well neutralized by enhancing cell viability by incorporation of CUM and/or KTP. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 42751.     

Development of antimicrobial‐loaded polyurethane films for drug‐eluting catheters

To prepare antibacterial, polymeric catheters for preventing catheter‐induced infections, sulfathiazole was loaded into polyurethane by solubilizing with solvents and the resultant films were cast. Fourier transform infrared spectroscopy confirmed the presence of sulfathiazole in the drug‐loaded polyurethane films. The thermal and mechanical properties of the films were assessed using differential scanning calorimetry and dynamic mechanical analysis. The drug‐loaded films were immersed in constantly stirred, deionized water at 37 °C for in vitro drug release study. The experimental data obtained from the in vitro drug release study were fit into mathematical models. Antibacterial efficiency of released sulfathiazole was evaluated by Escherichia coli growth inhibition test. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 46467.     

Solid lipid nanoparticles loaded thermoresponsive pluronic–xanthan gum hydrogel as a transdermal delivery system

The aim of this study was to develop and investigate thermoresponsive hydrogel incorporating curcumin (Cur) for application as a transdermal delivery system. Cur was encapsulated within solid lipid nanoparticles via ultrasonic homogenization, and these were introduced into a thermoresponsive hydrogel composed of pluronic F68 (PF68) and F127 (PF127). The hydrogel composed of PF68 and PF127 in 10:90 ratio transformed from sol to gel at 29.3 °C close to skin temperature. The skin adhesiveness and adhesive strength of the hydrogel with 0.2% (w/w) of XG was 1.64 and 1.24 times higher than those of the hydrogel without XG, respectively. The physiochemical characteristics of prepared formulations were investigated via observation of particle size, polydispersity index, transmission electron microscopy, and scanning electron microscopy. Moreover, Fourier transform infrared spectroscopy analysis was performed at physiological temperature, which revealed lower hydrogen bonding intensity at gel phase than at sol phase. The cumulative amount of Cur that penetrated significantly increased compared with the Cur ethanol solution. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 46004.     

Amorphous poly(3‐hydroxybutyrate) nanoparticles prepared with recombinant phasins and PHB depolymerase

Phasin protein (PhaP) is known to anchor into the matrix of phospholipid surrounding polyhydroxyalkanoic acid (PHA) inclusion bodies formed in bacterial cells and regulate the size of the granules, as well as the number of PHA granules. To investigate the effect of phasin on the formation of artificial poly(3‐hydroxybutyrate) (P(3HB)) granules in vitro, (His)₆‐tagged or GST‐fusion recombinant phasin was prepared and utilized for the artificial granule preparation. In addition, a P(3HB) depolymerase was coloaded with the recombinant phasin to prepare self‐degradable phasin‐coated P(3HB) granules. A water/chloroform two‐phase emulsion technique was used, in which the emulsification was carried out by sonication, and the chloroform in the emulsion was removed by stirring‐aided evaporation at room temperature or 65°C. Slower chloroform removal at room temperature produced better spherically shaped P(3HB) nanogranules, which were uniformly sized (～100 to 200 nm in diameter). The self‐degradability of P(3HB) depolymerase‐loaded P(3HB) nanogranules was investigated. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 41074.     

Biodegradable polymeric injectable implants for long‐term delivery of contraceptive drugs

Development of injectable, long‐lasting, contraceptive drug delivery formulations, and implants are highly desired to avoid unplanned pregnancies while improving patient compliance and reducing adverse side effects and treatment costs. The present study reports on the fabrication and characterization of two levonorgestrel (LNG) microsphere injectable formulations. Poly(?‐caprolactone) (PCL) with 12.5% and 24% (w/w) LNG were fabricated into microspheres, measuring 300 ± 125 µm, via the oil‐in‐water (o/w) emulsion solvent evaporation technique. Formulations showed sustained drug release up to 120 days. FTIR, XRD, DSC, and TGA confirmed the absence of LNG chemical interaction with PCL as well as its molecular level distribution. The in vitro release of LNG was calculated to be Fickian diffusion controlled and properly characterized. The inclusion of multiple elevated release temperatures allowed for the application of the Arrhenius model to calculate drug release constants and representative sampling intervals, demonstrating the use of elevated temperatures for accelerated‐time drug release studies. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 46068.     

Thermoresponsive hollow magnetic microspheres with hyperthermia and controlled release properties

Thermoresponsive hollow magnetic microspheres consisting of a hollow magnetic core, a carbon shell, and a smart polymer layer are presented in this article. A carbon nanomaterial was used as a steric stabilizer for Fe₃O₄ nanoparticles and a supporter for polymer. The thermoresponsive monomer, N‐isopropyl acrylamide, was grafted on the carbon‐encapsulate hollows by surface radical polymerization. The experimental results indicate that the composites had a phase‐transition temperature around 43°C and a saturation magnetization of 56.9 emu/g; this showed apparent thermosensitivity and magnetism. The performances in hyperthermia evaluated by an inductive magnetic field showed that the hybrid microspheres had a specific absorption rate of 240 W/g. The model drug, 5‐fluorouracil, was loaded in and released from the microspheres with different release rates at 35 and 50°C. This demonstrated that the as‐synthesized microspheres had a thermotriggered release ability and would be a good drug carrier in the biomedical field. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42617.