PLGA Particles Research Articles

Chitosan based nanoparticles functionalized with peptidomimetic derivatives for oral drug delivery

The goal of this study was to develop an optimized drug delivery carrier for oral mucosa applications able to release in situ bioactive molecules by using biopolymeric materials. Among them chitosan and poly(lactic-co-glycolic acid) (PLGA) have gained considerable attention as biocompatible carriers able to improve the delivery of active agents. The formulation of such vehicles in the form of nanoparticles (NPs) could permit to exploit the peculiar properties of nanomaterials in order to enhance the efficacy of active agents. Chitosan (CS) and PLGA chlorexidine dihydrochloride (CHX)-loaded NPs were synthesized by ionotropic gelation and osmosis based methodology respectively. In order to facilitate NPs adhesion on human dental surfaces, two different strategies were employed: PLGA particles with an external shell of CS to produce a positive surface charge allowing CHX loaded PLGA NPs to interact with the negative charged dental surfaces, while CS particles were functionalized with peptidomimetic derivative glutathione (GSH). The morphology was investigated by scanning electron microscopy. A sustained release profile of CHX from CS NPs was achieved. CS-based NPs adhered on human tooth surfaces in a simulated brushing and rinsing process and their in vitro toxicity evaluation on Human Gingival Fibroblasts (HGFs) was between 20 and 60% in all experimental conditions. Thanks to their adhesion properties and low cytotoxicity, the synthesized CS-based formulations may be efficiently exploited for therapy purposes or to enhance in vivo dental care (i.e. preparation of toothpastes or other cosmetics for daily oral care).

Facile technique for the preparation of monodispersed biodegradable polymer nanospheres using a solvent evaporation method

Abstract A facile technique was developed for the preparation of monodispersed nanospheres composed of poly(lactide-co-glycolide) (PLGA) for use as a biodegradable polymer in a liquid–liquid system. The preparation of PLGA particles by solvent evaporation from an emulsion prepared by adding a nonionic or reactive surfactant to the water phase was examined. The size of the PLGA particles gradually decreased as the surfactant concentration in the water phase increased. However, nanosized PLGA particles were difficult to prepare using this procedure. Preparation of nanosized particles of PLGA by solvent evaporation from a mixture of an aqueous solution of polyvinylalcohol (PVA) and ethanol was also examined. As the amount of ethanol was increased relative to the amount of PVA solution, the size of the PLGA particles decreased. At a ratio of 50:40 v/v% PVA(aq):ethanol, monodispersed spherical PLGA particles, 170 nm in diameter, were generated. Nanosized PLGA particles in liquid–liquid systems are generally prepared using solvent evaporation methods after emulsion droplets are first prepared using a particulate disperser apparatus (e.g., an ultrasonic homogenizer), although the resulting particles are polydispersed. In this study, monodispersed nanosized PLGA particles were generated even though we used a simple high-speed rotary homogenizer, which is usually not capable of preparing nanosized particles, without the use of a particulate mechanical disperser or a combination of particulate emulsion techniques. The technique used in this study may also be applicable to the preparation of other types of polymers and emulsion particles.

Electrospraying technique for the fabrication of metronidazole contained PLGA particles and their release profile.

Advanced engineering of materials for the development of drug delivery devices provides scope for novel and versatile strategies for treatment of various diseases. 'Electrospraying' was used to prepare PLGA microparticles and further encapsulate the drug, metronidazole (Met) within the particles to function as a drug delivery system. Two different solvents were utilized for the preparation of drug loaded PLGA particles, whereby the polymeric solution in dichloromethane (DCM) produced particles of bigger sizes than using trifluoroethanol (TFE). Scanning electron microscopy showed the spherical morphology of the particles, with sizes of 3946±407nm and 1774±167nm, respectively for PLGA-Met(DCM) and PLGA-Met(TFE). The FTIR spectroscopy proved the incorporation of metronidazole in the polymer, but without any specific drug-polymer interaction. The release of the drug from the particles was studied in phosphate buffered saline, where a sustained drug release was obtained for at least 41days. Cytotoxicity evaluation of the drug extract using mesenchymal stem cells (MSCs) showed not hindering the proliferation of MSCs, and the cell phenotype was retained after incubation in the drug containing media. Electrospraying is suggested as a cost-effective and single step process for the preparation of polymeric microparticles for prolonged and controlled release of drug.

45S5Bioglass®-based scaffolds coated with selenium nanoparticles or with poly(lactide-co-glycolide)/selenium particles: Processing, evaluation and antibacterial activity

In the bone tissue engineering field, there is a growing interest in the application of bioactive glass scaffolds (45S5Bioglass®) due to their bone bonding ability, osteoconductivity and osteoinductivity. However, such scaffolds still lack some of the required functionalities to enable the successful formation of new bone, e.g. effective antibacterial properties. A large number of studies suggest that selenium (Se) has significant role in antioxidant protection, enhanced immune surveillance and modulation of cell proliferation. Selenium nanoparticles (SeNp) have also been reported to possess antibacterial as well as antiviral activities. In this investigation, uniform, stable, amorphous SeNp have been synthesized and additionally immobilized within spherical PLGA particles (PLGA/SeNp). These particles were used to coat bioactive glass-based scaffolds synthesized by the foam replica method. Samples were characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS) and transmission electron microscopy (TEM). SeNp, 45S5Bioglass®/SeNp and 45S5Bioglass®/PLGA/SeNp showed a considerable antibacterial activity against Gram positive bacteria, Staphylococcus aureus and Staphylococcus epidermidis, one of the main causative agents of orthopedic infections. The functionalized Se-coated bioactive glass scaffolds represent a new family of bioactive, antibacterial scaffolds for bone tissue engineering applications.

In vitro and in vivo evaluation of Δ9-tetrahidrocannabinol/PLGA nanoparticles for cancer chemotherapy

Nanoplatforms can optimize the efficacy and safety of chemotherapy, and thus cancer therapy. However, new approaches are encouraged in developing new nanomedicines against malignant cells. In this work, a reproducible methodology is described to prepare Δ9-tetrahidrocannabinol (Δ9-THC)-loaded poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles against lung cancer. The nanoformulation is further improved by surface functionalization with the biodegradable polymers chitosan and poly(ethylene glycol) (PEG) in order to optimize the biological fate and antitumor effect. Mean nanoparticle size (≈290nm) increased upon coating with PEG, CS, and PEG–CS up to ≈590nm, ≈745nm, and ≈790nm, respectively. Surface electrical charge was controlled by the type of polymeric coating onto the PLGA particles. Drug entrapment efficiencies (≈95%) were not affected by any of the polymeric coatings. On the opposite, the characteristic sustained (biphasic) Δ9-THC release from the particles can be accelerated or slowed down when using PEG or chitosan, respectively. Blood compatibility studies demonstrated the adequate in vivo safety margin of all of the PLGA-based nanoformulations, while protein adsorption investigations postulated the protective role of PEGylation against opsonization and plasma clearance. Cell viability studies comparing the activity of the nanoformulations against human A-549 and murine LL2 lung adenocarcinoma cells, and human embryo lung fibroblastic MRC-5 cells revealed a statistically significant selective cytotoxic effect toward the lung cancer cell lines. In addition, cytotoxicity assays in A-549 cells demonstrated the more intense anticancer activity of Δ9-THC-loaded PEGylated PLGA nanoparticles. These promising results were confirmed by in vivo studies in LL2 lung tumor-bearing immunocompetent C57BL/6 mice.

A Multioptimization Approach to Assessment of Drug Delivery of PLGA Nanoparticles: Simultaneous Control of Particle Size and Release Behavior

A multiple optimization strategy was implemented on the experimental data obtained in this study to assess drug-delivery behavior of poly(D,L-lactide-co-glycolide) (PLGA) particles. Albumin–fluorescein isothiocyanate conjugate (FITC-albumin)-loaded PLGA micro- and nanoparticles were prepared by water-in-oil-in-water double emulsion method. The experiments were carried out based on L8 Taguchi design where the effects of PLGA molecular weight, PLGA concentration in the oil phase, and sonication rate in the second emulsification step of preparation process on particle size and percentage of initial burst release of PLGA were discussed. Multioptimization toward PLGA particle size and initial burst elucidated that all aforementioned variables affect the characteristics of PLGA particles, but PLGA molecular weight was appeared as the most significant factor among studied variables. Multifarious optimizations were tested and executed varying the aforementioned factors to minimize both the size and percentage of initial burst of PLGA particles. The FTIR experiment of the optimal formulation showed the successful incorporation of the drug into the particles. These results enable careful selection and definition of optimal process parameters for the preparation of PLGA nanoparticles with sustained release properties. Furthermore, the methodology developed in this work introduces a useful tool to meet a drug delivery system with optimal release behavior.

Controlled delivery of stromal derived factor-1α from poly lactic-co-glycolic acid core–shell particles to recruit mesenchymal stem cells for cardiac regeneration

Stromal derived factor-1α (SDF-1α) has shown promising results in treatment of myocardial infarction (MI), via recruitment of endogenous stem cells into the injured myocardium. However, the bioactivity of this susceptible signalling chemokine is reduced significantly during the common fabrication processes of drug delivery systems, due to the exposure to organic–aqueous interfaces or elevated temperature. In this study, we developed a novel SDF-1α delivery system using coaxial electrospraying, the technique which enables fabrication of core–shell particles with minimized contact of organic-aqueous phases. The SDF-1α incorporated PLGA particles exhibited distinct core–shell structure, confirmed by transmission electron microscopy (TEM). Controlled release of SDF-1α was obtained for at least 40days, and the release rate was tailored by co-encapsulation of bovine serum albumin (BSA) into the core of the particles. The SDF-1α released from PLGA/SDF-1α and PLGA/BSA-SDF-1α particles retained its chemotactic activity, and enhanced the number of migrated mesenchymal stem cells (MSCs) by 38% and 54%, respectively, compared to basal medium used as the control. Moreover, both SDF-1α and BSA supported the proliferation of MSCs within 3days of cell culture. The SDF-1α incorporated core–shell particles developed by electrospraying technique, can be effectively employed as injectable drug delivery system for in situ cardiac regeneration.

Cellobiose-coated poly (lactide-co-glycolide) particles loaded with diphtheria toxoid for per os immunization

AimTo evaluate the dose-dependent immunogenic properties of poly (lactide-co-glycolide) (PLGA) particles coated with cellobiose as antigen carriers for oral immunization.MethodsTwo types of PLGA-cellobiose particles (PLGA-cellobiose-1, ~ 0.8 μm and PLGA-cellobiose-2, ~ 1.2 μm) containing non-toxic recombinant subunit B (SbB) of diphtheria toxin fused with enhanced green fluorescent protein were characterized in vitro for their size, shape, antigen loading, and ability to induce phagocytosis. Different doses of antigen, immobilized on the particles (2.5 μg, 25 μg, 250 μg, and 2500 μg per 1 kg of body weight), were administered per os 3 times with intervals of 2 weeks to BALB/c female mice. The antigen-specific IgG and IgA antibodies were estimated in serum by ELISA.ResultsAfter the first immunization, increase in concentration of blood antitoxic antibodies was detected. Antigen dose 250 μg/kg was the most immunogenic for IgG antibodies induction for both types of PLGA-cellobiose particles. Antigen doses 25 μg/kg and 2.5 μg/kg were the most immunogenic for IgA antibodies induction by PLGA-cellobiose 1 and 2 particles, respectively. The second and the third treatment had no significant effect on the immune response or even reduced it, which could be explained by immune tolerance induction by the antigens delivered per os.ConclusionOur results suggest that the correct dose of PLGA-cellobiose particles loaded with antigen could significantly increase the humoral immune response against the introduced antigen already after the first immunization. Thus, PLGA particles can be considered as a potent component of oral vaccines.

Novel PLGA-based nanoparticles for the oral delivery of insulin

BackgroundInsulin is the drug therapy for patients with insulin-dependent diabetes mellitus. A number of attempts have been made in the past to overcome the problems associated with the oral delivery of insulin, but with little success. Orally administered insulin has encountered with many difficulties such as rapid degradation and poor intestinal absorption. The potential use of D-α-tocopherol poly(ethylene glycol) 1000 succinate (TPGS)-emulsified poly(ethylene glycol) (PEG)-capped poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) was investigated for sustained delivery of insulin (IS).ObjectiveTo investigate the efficacy of TPGS-emulsified PEG-capped PLGA NPs (TPPLG NPs) as a potential drug carrier for the oral delivery of insulin.MethodsA series of biodegradable low-molecular-weight PLGA (80/20 [PLG4] and 70/30 [PLG6]) copolymers were synthesized by melt polycondensation. The commercial insulin-loaded TPGS-emulsified PEG-capped PLGA NPs (ISTPPLG NPs) were synthesized by water–oil–water emulsion solvent evaporation method. The physical and chemical properties of PLGA copolymers, particle size, zeta potential, and morphology of the NPs were examined. The in vivo studies of ISTPPLG NPs were carried out in diabetic rats by oral administration.ResultsThe maximum encapsulation efficiency of ISTPPLG6 NPs was 78.6%±1.2%, and the mean diameter of the NPs was 180±20 nm. The serum glucose level was significantly (twofold) decreased on treatment with ISTPPLG NPs, and there was a threefold decrease with insulin-loaded PLGA (70/30) NPs when compared to that of free insulin-treated diabetic rats. The results show that the oral administration of ISTPPLG6 NPs is an effective method of reducing serum glucose level for a period of 24 hours. Histopathological studies reveal that ISTPPLG NPs could restore the damage caused by streptozotocin in the liver, kidneys, and pancreas, indicating its biocompatibility and regenerative effects.ConclusionISTPPLG6 NPs can act as potential drug carriers for the oral delivery of insulin.

Poly-(lactic-co-glycolic-acid)-based particulate vaccines: Particle uptake by dendritic cells is a key parameter for immune activation

Poly(lactic-co-glycolic acid) (PLGA) particles have been extensively studied as biodegradable delivery system to improve the potency and safety of protein-based vaccines. In this study we analyzed how the size of PLGA particles, and hence their ability to be engulfed by dendritic cells (DC), affects the type and magnitude of the immune response in comparison to sustained release from a local depot. PLGA microparticles (MP, volume mean diameter≈112μm) and nanoparticles (NP, Z-average diameter≈350nm) co-encapsulating ovalbumin (OVA) and poly(I:C), with comparable antigen (Ag) release characteristics, were prepared and characterized. The immunogenicity of these two distinct particulate vaccines was evaluated in vitro and in vivo. NP were efficiently taken up by DC and greatly facilitated MHC I Ag presentation in vitro, whereas DC cultured in the presence of MP failed to internalize significant amounts of Ag and hardly showed MHC I Ag presentation. Vaccination of mice with NP resulted in significantly better priming of Ag-specific CD8+ T cells compared to MP and OVA emulsified with incomplete Freund's adjuvant (IFA). Moreover, NP induced a balanced TH1/TH2-type antibody response, compared to vaccinations with IFA which stimulated a predominant TH2-type response, whereas MP failed to increase antibody titers. In conclusion, we postulate that particle internalization is of crucial importance and therefore particulate vaccines should be formulated in the nano- but not micro-size range to achieve efficient uptake, significant MHC class I cross-presentation and effective T and B cell responses.

Monitoring the intracellular transformation process of surface-cleavable PLGA particles containing disulfide bonds by fluorescence resonance energy transfer.

A great number of stimuli-responsive particles have been developed and used for biomedical applications such as intracellular drug delivery. It is of paramount importance to study the intracellular responsive process of these particles, offering insight into the understanding of their structure variation and design criteria for better performance. In this study polyethyleneimine (PEI)-coated poly(lactide-co-glycolide) (PLGA) particles with a diameter of 430 nm were prepared via a one-step emulsion method. The amino groups in the PEI molecules allowed further covalent linking of fluorescein isothiocyanate (FITC), bifunctional coupling agents 3,3'-dithiobispropionimidate, amino-ended polyethylene glycol (NH2-PEG-NH2) and tetramethylrhodamine isothiocyanate (TRITC), resulting in fluorescence resonance energy transfer (FRET) pairs on the particles. The particles exhibited glutathione-responsive ability, and lost the FRET effect due to the separation of FITC/TRITC pairs from the particle surface as a result of the cleavage of disulfide bonds. The particles showed different FRET change rates in A549 cells and HEK293 cells depending on the intracellular GSH concentration. Moreover, a much slower degradation rate was found inside cells than in simulated buffer with a similar GSH concentration. The results suggest that the responsive behaviors of the particles obtained in simulated buffer may not match fully/correctly with the real situation in a complicated intracellular environment.

Preparation and characterization of nickel chelating functionalized poly (lactic-co-glycolic acid) microspheres

Abstract The preparation of poly (lactic-co-glycolic acid) spheres functionalized with tri-(nitrilotriacetic acid) (NTA) employing a double-emulsion and evaporation method is described. First, polyacrylic acid (PAA) employed as emulsion stabilizer was chemically modified with NTA to yield modified PAA (PAA-NTA). PAA-NTA was characterized by 1H-NMR, ATR-FTIR spectroscopy and thermogravimetric analysis (TGA). Scanning electron microscopy (SEM) was employed to characterize the morphology and particle size distribution of PLGA spheres obtained with both type of surfactants, PAA and PAA-NTA. Finally, we proved that PLGA particles obtained with modified PAA are able to chelate nickel ions, key for the development of future biomedical applications for these materials.

Self-setting particle-stabilized emulsion for hard-tissue engineering

Injectable self-setting materials have recently attracted interest for use in minimally invasive medical treatments and tissue engineering. In particular, calcium phosphate cements (CPCs) offer certain specific advantages for the treatment of bone defects. Although the inner structures of set CPCs are important for the apposition and remodeling of new bone, there are still limitations to the design of cements with a well-controlled inner structure.In the present study, we explored self-setting CPCs that generate interconnected macroporous matrices using solid-particle-stabilized emulsion templates. α-Tricalcium phosphate (α-TCP) and poly(ethylene phosphate) sodium salt-coated poly(d,l-lactide-co-glycolide) (PLGA) microparticles were mixed with castor oil and water to form an oil-in-water (o/w) emulsion. The α-TCP and PLGA microparticles functioned as an effective particulate emulsifier by adsorption at the oil–water interface. The resulting emulsion spontaneously set in a humidified atmosphere at ambient temperature. The setting behaviors of different emulsions were characterized through X-ray diffraction analysis and compressive-strength measurements. The PLGA microparticles did not hinder the rate of hardening of the emulsions, and they improved the compressive strengths of the set cements. The PLGA particles incorporated within the set cements were hydrolytically degraded, and the degradation of the PLGA particles resulted in the formation of an interconnected pore structure in the set cement. Finally, mouse osteoblastic (MC3T3-E1) cells were cultivated on the set CPCs. The adherent MC3T3-E1 cells adopted a spindle shape, and significant cellular invasion into the set CPCs was observed after degradation of the PLGA microparticles. In conclusion, self-setting emulsions stabilized with α-TCP and PLGA microparticles constitute a novel candidate material for bone regeneration.

In vitro and in vivo study of fluorescent probe PLGA particles prepared by premix membrane emulsification method

Relatively uniform-sized nanoparticles made of poly (lactic-co-glycolic acid) (PLGA) were prepared by premix membrane emulsification method. After the drug loading property was completed, the dynamic tissue distribution of nanoparticles was recorded. With the average particle size and span as indexes, membrane pore size, number of passing membrane times, membrane pressure, volume ratio of oil-water phase and the concentration of poly(vinyl alcohol) (PVA) in external water phase were investigated by single factor test, the optimum preparation technology of blank PLGA nanlparticles was as following: pore size of SPG membrane was 1 μm, membrane pressure was 1. 15 MPa, the number of passing membrane time was 3, the mass fraction of PVA of 2%, volume ratio of oil-water phase of 1 : 5. Prepared nanoparticles were round with smooth surface, the mean diameter was 332.6 nm, span was 0.010, the confocal laser scanning microscope (CLSM) concluded that fluorescent substance is uniform composizion in PLGA nanoparticle, and the in vivo imaging technology in mice include that the nanoparticles show good liver and spleen targeting property.

Synthesis and characterisation of poly(lactide-co-glycolide) nanospheres using vitamin E emulsifier prepared through one-step oil-in-water emulsion and solvent evaporation techniques.

Nanoparticulate drug delivery systems are of considerable therapeutic interest for delivery of drugs across from the blood-brain barrier. In this study, the ability of sodium chloride (NaCl) and different percentages of a water-soluble form of natural vitamin E, on the formation of poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs), as a potential carrier for drug delivery, was investigated. According to the obtained results, by increasing the percentage of natural vitamin E, the average particle size decreased and the range of diameters came closer. After using 0.26 w/v % vitamin E, the average size of the PLGA particles became <100 nm. Moreover, the particles containing NaCl led to the formation of even smaller particles. In addition, no obvious cytotoxicity was observed at various natural vitamin E amounts in one and three days, and the modified PLGA NPs could be considered biocompatible since they showed a little decrease in cellular viability.

Poly (lactic-co-glycolic acid) particles prepared by microfluidics and conventional methods. Modulated particle size and rheology

HypothesisMicrofluidic techniques are expected to provide narrower particle size distribution than conventional methods for the preparation of poly (lactic-co-glycolic acid) (PLGA) microparticles. Besides, it is hypothesized that the particle size distribution of poly (lactic-co-glycolic acid) microparticles influences the settling behavior and rheological properties of its aqueous dispersions. ExperimentsFor the preparation of PLGA particles, two different methods, microfluidic and conventional oil-in-water emulsification methods were employed. The particle size and particle size distribution of PLGA particles prepared by microfluidics were studied as a function of the flow rate of the organic phase while particles prepared by conventional methods were studied as a function of stirring rate. In order to study the stability and structural organization of colloidal dispersions, settling experiments and oscillatory rheological measurements were carried out on aqueous dispersions of PLGA particles with different particle size distributions. FindingsMicrofluidics technique allowed the control of size and size distribution of the droplets formed in the process of emulsification. This resulted in a narrower particle size distribution for samples prepared by MF with respect to samples prepared by conventional methods. Polydisperse samples showed a larger tendency to aggregate, thus confirming the advantages of microfluidics over conventional methods, especially if biomedical applications are envisaged.

Brain-penetrating nanoparticles improve paclitaxel efficacy in malignant glioma following local administration.

Poor drug distribution and short drug half-life within tumors strongly limit efficacy of chemotherapies in most cancers, including primary brain tumors. Local or targeted drug delivery via controlled-release polymers is a promising strategy to treat infiltrative brain tumors, which cannot be completely removed surgically. However, drug penetration is limited with conventional local therapies since small-molecule drugs often enter the first cell they encounter and travel only short distances from the site of administration. Nanoparticles that avoid adhesive interactions with the tumor extracellular matrix may improve drug distribution and sustain drug release when applied to the tumor area. We have previously shown model polystyrene nanoparticles up to 114 nm in diameter were able to rapidly diffuse in normal brain tissue, but only if coated with an exceptionally dense layer of poly(ethylene glycol) (PEG) to reduce adhesive interactions. Here, we demonstrate that paclitaxel (PTX)-loaded, poly(lactic-co-glycolic acid) (PLGA)-co-PEG block copolymer nanoparticles with an average diameter of 70 nm were able to diffuse 100-fold faster than similarly sized PTX-loaded PLGA particles (without PEG coatings). Densely PEGylated PTX-loaded nanoparticles significantly delayed tumor growth following local administration to established brain tumors, as compared to PTX-loaded PLGA nanoparticles or unencapsulated PTX. Delayed tumor growth combined with enhanced distribution of drug-loaded PLGA-PEG nanoparticles to the tumor infiltrative front demonstrates that particle penetration within the brain tumor parenchyma improves therapeutic efficacy. The use of drug-loaded brain-penetrating nanoparticles is a promising approach to achieve sustained and more uniform drug delivery to treat aggressive gliomas and potentially other brain disorders.

Encapsulated particles attached on electrospun fibers by in situ combination of electrospinning and coaxial electrospraying.

Electrohydrodynamic jetting has been widely used as a promising strategy for the development of functionalized scaffolds to mimic natural extracellular matrix. The current electrospun scaffolds achieve functionality through additional mechanical or chemical treatments, and their life-time depends on fiber degradation. An innovative in situ approach used to attach core-shell poly(D,L-lactide-co-glycolide) (PLGA) particles on fibrous mats is described here. This particle/fiber composite was prepared by electrohydrodynamic jetting of countercharged nozzles (EJC) based on neutralization between electrospun nanofibers and coaxial electrosprayed droplets. The PLGA particles were successfully attached onto both water-soluble polyvinylpyrrolidone and hydrophobic poly(L-lactide-co-D,L-lactide). The resulting release rates of encapsulated model compounds were independently controlled by fiber degradation. Encapsulation efficiency and the dimensions of particles and fibers were easily engineered by changing solvents. The particle/fiber composite prepared by EJC could be a superior material for developing future biomaterials with architectured biological and mechanical properties.

Laser‐Activatible PLGA Microparticles for Image‐Guided Cancer Therapy In Vivo

Poly(lactide‐co‐glycolic acid) (PLGA) particles are biocompatible and bio­degradable, and can be used as a carrier for various chemotherapeutic drugs, imaging agents and targeting moieties. Micrometer‐sized PLGA particles were synthesized with gold nanoparticles and DiI dye within the PLGA shell, and perfluorohexane liquid (PFH) in the core. Upon laser irradiation, the PLGA shell absorbs the laser energy, activating the liquid core (liquid conversion to gas). The rapidly expanding gas is expelled from the particle, resulting in a microbubble; this violent process can cause damage to cells and tissue. Studies using cell cultures show that PLGA particles phagocytosed by single cells are consistently vaporized by laser energies of 90 mJ cm−2, resulting in cell destruction. Rabbits with metastasized squamous carcinoma in the lymph nodes are then used to evaluate the anti‐cancer effects of these particles in the lymph nodes. After percutaneous injection of the particles and upon laser irradiation, through the process of optical droplet vaporization, ultrasound imaging shows a significant increase in contrast in comparison to the control. Histology and electron microscopy confirm damage with disrupted cells throughout the lymph nodes, which slows the tumor growth rate. This study shows that PLGA particles containing PFC liquids can be used as theranostic agents in vivo.

Influence of surface coatings of poly(d,l-lactide-co-glycolide) particles on HepG2 cell behavior and particle fate

This study is focused on the intracellular fate of poly(d,l-lactide-co-glycolide) (PLGA) particles with different surface coatings after cellular uptake, and their influence on the functions of human liver cancer cells (HepG2 cells). The PLGA particles coated with polyethyleneimine (PEI) and bovine serum albumin (BSA) with a similar diameter of ∼400 nm but different surface chemistry were prepared. The intracellular distribution of the PLGA particles was also largely dependent on their surface coatings. The PLGA-PEI particles were removed from cells by exocytosis with a slower rate compared to the PLGA-BSA particles. In general, uptake of both types of the PLGA particles did not cause apparent impedance on cell viability and cell cycle, but uptake of the PLGA-PEI particles did have certain influence on cell functions such as intracellular level of reactive oxygen species, cytoskeleton organization, cell migration, and secretion levels of triglyceride.