PLGA Particles Research Articles

Advanced microfluidic techniques for in situ PLGA microparticle formation: A dynamic solvent extraction approach

Microencapsulation processes often use the "solvent extraction/evaporation" technique, which involves (i) dissolving a polymer in an organic solvent (optionally with a bioactive component), (ii) forming microdroplets, (iii) removing the solvent, and finally (iv) harvesting and drying the particles ex situ. These last two steps lack control over the solidification processes, which adversely affects the morphology and size distribution of the final microparticles. In this study, we present a continuous production process for solid PLGA microparticles within a microfluidic chip, covering droplet formation, solvent extraction, and solidification. This method offers the advantage of enhanced control over the solidification process within a closed system, leading to morphologically uniform particles. The setup includes a co-axial junction integrated into a chip with an 80 cm long serpentine channel. We generated droplets with various PLGA/ethyl acetate concentrations and tracked their shrinkage until solidification. Results showed that all droplets underwent identical shrinkage processes with consistent rates, velocity profiles, and sizes. The shrinkage rate was linear and unaffected by PLGA concentration, which only influenced final particle size.To demonstrate our setup's advantages, we compared it with the conventional off-chip method, where droplets shrink in a beaker. Off-chip shrinkage was non-linear and inconsistent, influenced by factors such as the number of surrounding droplets and production time. Droplets produced within a 10-s difference had solidification delays up to 250 s. In contrast, on-chip production was uniform, predictable, and 4–10 times faster. SEM imaging confirmed that on-chip particles were consistently spherical with a rough, wrinkled surface, unlike the irregular, bumpy off-chip particles.In summary, on-chip production and shrinkage of PLGA particles is faster and produces more uniformly shaped particles compared to off-chip methods. This study suggests that on-chip production could significantly enhance the efficiency and quality of drug-loaded microparticles, particularly for drug delivery applications.

Sustained release of inactivated H1N1 virus from degradable microparticles for extended vaccination

Influenza vaccines administered as intramuscularly injected inactivated viruses or intranasally administered live-attenuated viruses usually provide short-term protection against influenza infections. Biodegradable particles that provide sustained release of the antigen has been studied as an approach to extend vaccine protection. Here, we investigate sustained release of ultraviolet killed influenza A virus (A/PR/8/34(H1N1)) (kPR8) loaded into poly(D,L-lactic-co-glycolic acid) (PLGA) microparticles. Particles were prepared using the double emulsion method, and polymer molecular weight (MW), polymer hydrophobicity, polymer concentration in the organic phase, and the amount of killed virus were varied to obtain a range of particles. Formulations included PLGA 50:50 (2–6, 7–17 kDa), PLGA 75:25 (4–15 kDa), and 50/50 PLGA 75:25 (4–15 kDa)/PCL (14 kDa). Additionally, NaOH was co-encapsulated in some cases to enhance particle degradation. The structure of the particles was explored by size measurements and electron microscopy. The kPR8 release profiles were measured using hemagglutinin ELISA. The concentration of the polymer (PLGA) in the organic phase and polymer MW significantly influenced virus loading, while polymer MW and co-encapsulation of NaOH modulated the release profiles. Mice receiving a single intramuscular injection of NaOH microparticle-encapsulated kPR8 were partially protected against a lethal influenza challenge 32 weeks post immunization. Microparticle (MP) vaccination induced a gradual increase in PR8-specific IgGs dominated by IgG1 in contrast to the rapid IgG2a-biased response elicited by soluble kPR8 immunization. Our results indicate that vaccine-NaOH co-loaded PLGA particles show potential as a single dose vaccination strategy for extended protection against influenza virus infection.

Diffusion of curcumin in PLGA-based carriers for drug delivery: a molecular dynamics study

Context:The rapid growth and diversification of drug delivery systems have been significantly supported by advancements in micro- and nano-technologies, alongside the adoption of biodegradable polymeric materials like poly(lactic-co-glycolic acid) (PLGA) as microcarriers. These developments aim to reduce toxicity and enhance target specificity in drug delivery. The use of in silico methods, particularly molecular dynamics (MD) simulations, has emerged as a pivotal tool for predicting the dynamics of species within these systems. This approach aids in investigating drug delivery mechanisms, thereby reducing the costs associated with design and prototyping. In this study, we focus on elucidating the diffusion mechanisms in curcumin-loaded PLGA particles, which are critical for optimizing drug release and efficacy in therapeutic applications.Methods:We utilized MD to explore the diffusion behavior of curcumin in PLGA drug delivery systems. The simulations, executed with GROMACS, modeled curcumin molecules in a representative volume element of PLGA chains and water, referencing molecular structures from the Protein Data Bank and employing the CHARMM force field. We generated PLGA chains of varying lengths using the Polymer Modeler tool and arranged them in a bulk-like environment with Packmol. The simulation protocol included steps for energy minimization, T and p equilibration, and calculation of the isotropic diffusion coefficient from the mean square displacement. The Taguchi method was applied to assess the effects of hydration level, PLGA chain length, and density on diffusion.Results:Our results provide insight into the influence of PLGA chain length, hydration level, and polymer density on the diffusion coefficient of curcumin, offering a mechanistic understanding for the design of efficient drug delivery systems. The sensitivity analysis obtained through the Taguchi method identified hydration level and PLGA density as the most significant input parameters affecting curcumin diffusion, while the effect of PLGA chain length was negligible within the simulated range. We provided a regression equation capable to accurately fit MD results. The regression equation suggests that increases in hydration level and PLGA density result in a decrease in the diffusion coefficient.

Curcumin‐Encapsulated Poly(lactic‐co‐glycolic acid) Nanoparticles: A Comparison of Drug Release Kinetics from Particles Prepared via Electrospray and Nanoprecipitation

AbstractControlled drug release (CDR) is a significant field of research in medical sciences due to its numerous clinical advantages over traditional methods. Encapsulation of a drug in a polymeric matrix is common technique to achieve CDR. In this study, drug‐polymer particles are prepared using poly(lactic‐co‐glycolic acid) (PLGA) as the polymer and curcumin (CUR) as model drug. Two different methods, electrospray and nanoprecipitation, are used to prepare the particles, and optimal samples in each process are selected based on size and polydispersity index (PDI). Samples are characterized using various tests, and entrapment efficiency (EE%) and drug loading (DL%) are calculated using UV spectroscopy. The results showed that nanoprecipitated and electrosprayed PLGA particles successfully encapsulated CUR, with higher encapsulation efficiency (93.2%) and loading capacity (7.2%) for electrosprayed particles. The in vitro drug release showed that electrospray particles have a slower release rate due to higher encapsulation efficiency. The electrospray method turned out to be more viable for synthesizing these polymer‐drug particles due to smaller particle size, lower PDI, higher entrapment efficiency, and drug loading percentage. Finally, the antibacterial behavior of the particles proved that prepared particles provide excellent antibacterial efficacy (99.9%) and can be used as drug delivery systems.

Evaluation of 3D-Printed Solid Microneedles Coated with Electrosprayed Polymeric Nanoparticles for Simultaneous Delivery of Rivastigmine and N-Acetyl Cysteine.

In the current study, coated microneedle arrays were fabricated by means of digital light processing (DLP) printing. Three different shapes were designed, printed, and coated with PLGA particles containing two different actives. Rivastigmine (RIV) and N-acetyl-cysteine (NAC) were coformulated via electrohydrodynamic atomization (EHDA), and they were incorporated into the PLGA particles. The two actives are administered as a combined therapy for Alzheimer's disease. The printed arrays were evaluated regarding their ability to penetrate skin and their mechanical properties. Optical microscopy and scanning electron microscopy (SEM) were employed to further characterize the microneedle structure. Confocal laser microscopy studies were conducted to construct 3D imaging of the coating and to simulate the diffusion of the particles through artificial skin samples. Permeation studies were performed to investigate the transport of the drugs across human skin ex vivo. Subsequently, a series of tape strippings were performed in an attempt to examine the deposition of the APIs on and within the skin. Light microscopy and histological studies revealed no drastic effects on the membrane integrity of the stratum corneum. Finally, the cytocompatibility of the microneedles and their precursors was evaluated by measuring cell viability (MTT assay and live/dead staining) and membrane damages followed by LDH release.

Development of paste-like organic/inorganic artificial bones compatible with bone remodeling cycles, consisting of β-tricalcium phosphate, calcium sulfate hemihydrate, and poly(lactic-co-glycolic acid) particles

Schematic illustration of organic/inorganic hybrid cement with the simultaneous addition of CSH and PLGA particles.

Polymeric Particle BAM15 Targeting Macrophages Attenuates the Severity of LPS-Induced Sepsis: A Proof of Concept for Specific Immune Cell-Targeted Therapy.

Macrophage polarization requires different energy sources and metabolic processes. Therefore, cell energy interference to alter macrophage functions has been proposed as a treatment for severe inflammatory diseases, including sepsis. In this study, targeting cell energy using BAM15 (a mitochondrial uncoupling agent) in human THP-1 and mouse RAW264.7 macrophages prominently interfered with M1 but not M2 polarization. Free BAM15 (BAM15) and BAM15-loaded PLGA particles (BAM15 particles) reduced the inflammatory response of M1 macrophages and enhanced the expression of M2 signature genes with the restoration of mitochondrial activity (extracellular flux analysis) in RAW264.7 cells. Furthermore, BAM15 particles but not BAM15 showed specific effects on the inflammatory response of macrophages but not neutrophils, and the particles were actively captured by splenic and liver macrophages in vivo. Administration of BAM15 and BAM15 particles attenuated the severity of sepsis in LPS-induced sepsis mice. Interestingly, BAM15 particles but not BAM15 alleviated LPS-induced liver injury by reducing hepatic inflammation. Our findings substantiate the superior efficacy of macrophage-targeted therapy using a BAM15 particle-delivery system and provide further support for clinical development as a potential therapy for severe inflammatory diseases.

A maghemite/PLGA (core/shell) nanostructure that may facilitate chemotherapy and antitumor hyperthermia

Failure of cancer therapy is typically associated to the poor accumulation of chemotherapeutics in tumor cells, the development of multidrug resistances, and the severe side effects. To beat the challenge, combined therapies against malignancies based on biodegradable nanosystems have emerged. Here, it is described the reproducible formulation of ≈ 270 nm-sized magnetic multicore PLGA particles. Characterization of the nanostructures by dynamic light scattering, electron microscopy, goniometry and electrophoresis confirmed the inclusion of hydrophobic maghemite nuclei in a polymeric nanomatrix. Adequate magnetic responsiveness was determined in vitro, while colloidal stability at 4 °C was demonstrated in short-term stability tests. Under the influence of an alternating electromagnetic field, the maghemite/PLGA (core/shell)-based colloid reached the minimum temperature of hyperthermia (≈ 42 °C) in ≈ 30 min. These heating capabilities made possible a significant decrease in the viability of T-84 cells (to ≈ 43 %). Finally, Cisplatin loading to the magnetopolymeric nanoparticles was characterized quantitatively by UV–Vis spectrophotometry (entrapment efficiency ≈ 82 %), and qualitatively by electrophoresis. The resulting Cisplatin-loaded magnetic multicore PLGA particles demonstrated a superior antitumor activity over the free chemotherapeutic in A-549 cells. These core/shell particles could be of interest for hyperthermia cancer treatment and chemotherapy.

Surface modified cationic PLGA microparticles as long-acting injectable carriers for intra-articular small molecule drug delivery

Controlled local delivery of therapeutics (small molecule drug crystals or biologics) for knee-associated diseases such as osteoarthritis necessitates patient compliance, ensuring that the injected depot does not trigger local tissue inflammation and immune responses. A local drug delivery strategy that releases drug at a controlled rate while ensuring minimal tolerability issues at the injection site would be an appealing paradigm in intra-articular (IA) therapies. Herein, we report the formulation development and characterization of surface modified PLGA microparticles (MPs) through the surface integration of a cationic lipid, DOTAP (1,2-Dioleoyl-3-trimethylammonium propane). Following IA administration, these particles are able to interact with anionic synovial fluid glycosaminoglycans (GAGs) to form an in-situ surface coating in the knee joint, thereby reducing the depot-associated local inflammatory response. The formulated microparticles were about 10–40 µm in size range, with a +19 to +33 mV overall surface charge after DOTAP lipid surface integration. These particles showed preferential surface adhesion with endogenous anionic GAGs (e.g., hyaluronic acid) due to electrostatic interactions in vitro, and approximately 65 % of the model drug triamcinolone acetonide (TCA) was released after 10 weeks in simulated synovial fluid. The uncoated and DOTAP-coated PLGA microparticles had no effect on mouse osteoblast MC3T3 cell viability and human macrophage inflammatory response. Further, DOTAP-coated particles showed a marginal decrease in pro-inflammatory cytokines in naïve rats following knee injection. Together, the results suggest that surface-modified PLGA particles may have promising potential as delivery carriers for long-acting injectables.

Precise surface functionalization of PLGA particles for human T cell modulation.

The biofunctionalization of synthetic materials has extensive utility for biomedical applications, but approaches to bioconjugation typically show insufficient efficiency and controllability. We recently developed an approach by building synthetic DNA scaffolds on biomaterial surfaces that enables the precise control of cargo density and ratio, thus improving the assembly and organization of functional cargos. We used this approach to show that the modulation and phenotypic adaptation of immune cells can be regulated using our precisely functionalized biomaterials. Here, we describe the three key procedures, including the fabrication of polymeric particles engrafted with short DNA scaffolds, the attachment of functional cargos with complementary DNA strands, and the surface assembly control and quantification. We also explain the critical checkpoints needed to ensure the overall quality and expected characteristics of the biological product. We provide additional experimental design considerations for modifying the approach by varying the material composition, size or cargo types. As an example, we cover the use of the protocol for human primary T cell activation and for the identification of parameters that affect ex vivo T cell manufacturing. The protocol requires users with diverse expertise ranging from synthetic materials to bioconjugation chemistry to immunology. The fabrication procedures and validation assays to design high-fidelity DNA-scaffolded biomaterials typically require 8 d.

Sorafenib-Loaded PLGA Carriers for Enhanced Drug Delivery and Cellular Uptake in Liver Cancer Cells.

Currently, conventional treatments of hepatocellular carcinoma (HCC) are not selective enough for tumor tissue and lead to multidrug resistance and drug toxicity. Although sorafenib (SOR) is the standard first-line systemic therapy approved for the clinical treatment of HCC, its poor aqueous solubility and rapid clearance result in low absorption efficiency and severely limit its use for local treatment. Herein, we present the synthesis of biodegradable polymeric Poly (D, L-Lactide-co-glycolide) (PLGA) particles loaded with SOR (PS) by emulsion-solvent evaporation process. The particles are carefully characterized focusing on particle size, surface charge, morphology, drug loading content, encapsulation efficiency, in vitro stability, drug release behaviour and tested on HepG2 cells. Additionally, PLGA particles have been coupled on side emitting optical fibers (seOF) integrated in a microfluidic device for light-triggered local release. PS have a size of 248 nm, tunable surface charge and a uniform and spherical shape without aggregation. PS shows encapsulation efficiency of 89.7% and the highest drug loading (8.9%) between the SOR-loaded PLGA formulations. Treating HepG2 cells with PS containing SOR at 7.5 µM their viability is dampened to 40%, 30% and 17% after 48, 129 and 168 hours of incubation, respectively. The high PS stability, their sustained release profile and the rapid cellular uptake corroborate the enhanced cytotoxicity effect on HepG2. With the prospect of developing biomedical tools to control the spatial and temporal release of drugs, we successfully demonstrated the potentiality of seOF for light-triggered local release of the carriers. Our prototypical system paves the way to new devices integrating microfluidics, optical fibers, and advanced carriers capable to deliver minimally invasive locoregional cancer treatments.

Weibull β value for the discernment of drug release mechanism of PLGA particles

Mathematical models are used to characterize and optimize drug release in drug delivery systems (DDS). One of the most widely used DDS is the poly(lactic-co-glycolic acid) (PLGA)-based polymeric matrix owing to its biodegradability, biocompatibility, and easy manipulation of its properties through the manipulation of synthesis processes. Over the years, the Korsmeyer-Peppas model has been the most widely used model for characterizing the release profiles of PLGA DDS. However, owing to the limitations of the Korsmeyer-Peppas model, the Weibull model has emerged as an alternative for the characterization of the release profiles of PLGA polymeric matrices. The purpose of this study was to establish a correlation between the n and β parameters of the Korsmeyer-Peppas and Weibull models and to use the Weibull model to discern the drug release mechanism. A total of 451 datasets describing the overtime drug release of PLGA-based formulations from 173 scientific articles were fitted to both models. The Korsmeyer-Peppas model had a mean Akaike Information Criteria (AIC) value of 54.52 and an n value of 0.42, while the Weibull model had a mean AIC of 51.99 and a β value of 0.55, and by using reduced major axis regression values, a high correlation was found between the n and β values. These results demonstrate the ability of the Weibull model to characterize the release profiles of PLGA-based matrices and the usefulness of the β parameter for determining the drug release mechanism.

Core-Shell Structured PLGA Particles Having Highly Controllable Ketoprofen Drug Release.

The non-steroid anti-inflammatory drug ketoprofen (KP) as a model molecule is encapsulated in different poly(lactide-co-glycolide) (PLGA) nanostructured particles, using Tween20 (TWEEN) and Pluronic F127 (PLUR) as stabilizers to demonstrate the design of a biocompatible colloidal carrier particles with highly controllable drug release feature. Based on TEM images the formation of well-defined core-shell structure is highly favorable using nanoprecipitation method. Stabile polymer-based colloids with ~200-210 nm hydrodynamic diameter can be formed by successful optimization of the KP concentration with the right choice of stabilizer. Encapsulation efficiency (EE%) of 14-18% can be achieved. We clearly confirmed that the molecular weight of the stabilizer thus its structure greatly controls the drug release from the PLGA carrier particles. It can be determined that ~20% and ~70% retention is available with the use of PLUR and TWEEN, respectively. This measurable difference can be explained by the fact that the non-ionic PLUR polymer provides a steric stabilization of the carrier particles in the form of a loose shell, while the adsorption of the non-ionic biocompatible TWEEN surfactant results in a more compact and well-ordered shell around the PLGA particles. In addition, the release property can be further tuned by decreasing the hydrophilicity of PLGA by changing the monomer ratio in the range of ~20-60% (PLUR) and 70-90% (TWEEN).

Tunable calcium phosphate cement formulations for predictable local release of doxycycline

Background Osteomyelitis is a bacterial infection, which leads to bone loss. Local treatment focuses on elimination of bacteria, which is preferable for simultaneous management of the bone defect after sequestrectomy and bone reconstruction in one-stage treatment of osteomyelitis. Calcium phosphate cements (CPCs) have attracted increased attention as bone substitute material because of their injectability and in situ self-setting properties, which allow for minimally invasive surgical procedures and local drug delivery.Methods We herein established a system to achieve different release profiles of the antibiotic drug doxycycline from CPC by finetuning their formulation. These CPC formulations were generated via facile addition of hydrolytically degrading PLGA particles, varying doses of doxycycline, and addition of the lubricant CMC.Results The CPC formulations exhibited appropriate handling properties in terms of injectability and setting time. Furthermore, doxycycline release profiles showed an adequate burst release followed by a cumulative release of up to 100% over a period of 8 weeks. Importantly, the released doxycycline retained its antibacterial activity against Staphylococcus aureus, the major pathogen causing osteomyelitis. Using an in vivo implantation model, antibacterial efficacy was demonstrated by a rapid decrease of inoculated S. aureus at the CPC surface and within surrounding tissues.Conclusions Our data show the versatility of the CPC system toward local antibacterial therapy, extending its application beyond bone substitution.

Photoresponsive liposomes and LipoParticles by incorporating a photosensitizer agent in their lipid membrane

Liposomes, as self-assembled lipid layer vesicles, have emerged as a promising platform for various biomedical applications such as photodynamic therapy (PDT). LipoParticles are core–shell lipid assemblies with a solid polymer core coated by a lipid membrane, which gather the advantages of both their counterparts. Photosensitizers (PS), used in PDT, are photosensitive molecules than can be activated by an exposure to a light source, leading to the death of pathogenic surrounding cells. In this context, the aim of this study is to elaborate liposomes and LipoParticles incorporating a PS, and to examine their resulting photoresponsive properties by following the release, triggered by an UV irradiation, of incorporated fluorescent (macro)molecules. Al(III) phthalocyanine chloride disulfonic acid (AlPcS2) was chosen as PS, and the release of 5(6)-carboxyfluorescein (CF) or bovine serum albumin conjugated with fluorescein isothiocyanate (BSA-FITC) from liposomes and poly (lactic-co-glycolic acid) (PLGA) core of LipoParticles respectively, was investigated by fluorescence spectroscopy. The results have shown that UV irradiation led to the release of CF molecules depending on the membrane lipid formulation, and that repeated irradiations could increase the amount of CF molecules released from liposomes. The main parameters governing the release of BSA-FITC macromolecules from LipoParticles were the temperature of their elaboration (corresponding to a reorganization of several liposomes on the surface of PLGA particles), the initial PS concentration, and the duration of UV irradiation. Best results were found with a temperature of the LipoParticles elaboration of 20 °C, a PS concentration of 0.1 mM, and a duration of irradiation of 5 min. These results support the fact that similarly to liposomes, LipoParticles can also be endowed with photoresponsive properties, which positions them as interesting nanovectors for PDT.

Preparation and evaluation of sustained release formulation of PLGA using a new injection system based on ink-jet injection technology

We developed a method for the preparation of PLGA particles exhibiting long-term sustained-release of entrapped drugs. The fine droplet drying (FDD) technology using a new injection system based on ink-jet injection technology was adapted as the preparation method. PLGA microspheres containing TRITC-dextran, acetaminophen, and albumin as model drugs were prepared by the FDD technology. The resultant microspheres were uniform in size, with average particle sizes ranging from 16.3 to 33.0 μm and SPAN factors ranging from 0.49 to 0.77. The encapsulation efficiency of drugs showed high values ranging from 75 to 99 wt% of the total amount of water-soluble drug contained in the particles. In an investigation of the optimal operation conditions of the FDD technology, the dew point temperature of the dryer air stream was found to be an important factor for controlling the initial burst of the prepared particles. The TRITC-dextran-containing PLGA microspheres were confirmed to exhibit long-term sustained release for about 90 days, and the mechanism was found to be PLGA degradation rate-limiting. Based on these results, we concluded that long-term sustained-released PLGA particles can be prepared by using FDD technology under a suitable drying condition for controlling the initial burst.

PLGA Particles in Immunotherapy

Poly(lactic-co-glycolic acid) (PLGA) particles are a widely used and extensively studied drug delivery system. The favorable properties of PLGA such as good bioavailability, controlled release, and an excellent safety profile due to the biodegradable polymer backbone qualified PLGA particles for approval by the authorities for the application as a drug delivery platform in humas. In recent years, immunotherapy has been established as a potent treatment option for a variety of diseases. However, immunomodulating drugs rely on targeted delivery to specific immune cell subsets and are often rapidly eliminated from the system. Loading of PLGA particles with drugs for immunotherapy can protect the therapeutic compounds from premature degradation, direct the drug delivery to specific tissues or cells, and ensure sustained and controlled drug release. These properties present PLGA particles as an ideal platform for immunotherapy. Here, we review recent advances of particulate PLGA delivery systems in the application for immunotherapy in the fields of allergy, autoimmunity, infectious diseases, and cancer.

LipoParticles: a lipid membrane coating onto polymer particles to enhance the internalization in osteoblast cells.

LipoParticles, core-shell assemblies consisting of a polymer core coated by a lipid membrane, are promising carriers for drug delivery applications with intracellular targets. This is of great interest since it is actually challenging to treat infections involving intracellular bacteria such as bone and joint infections where the bacteria are hidden in osteoblast cells. The present work reports for the first time to the best of our knowledge the proof of enhanced internalization of particles in osteoblast cells thanks to a lipid coating of particles (= LipoParticles). The ca. 300 nm-sized assemblies were elaborated by reorganization of liposomes (composed of DPPC/DPTAP 10/90 mol/mol) onto the surface of poly(lactic-co-glycolic acid) (PLGA) particles, and were characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM), and zetametry. Optimization of these assemblies was also performed by adding poly(ethylene glycol) (PEG) chains on their surface (corresponding to a final formulation of DPPC/DPTAP/DPPE-PEG5000 8/90/2 mol/mol/mol). Interestingly, this provided them colloidal stability after their 20-fold dilution in PBS or cell culture medium, and made possible their freeze-drying without forming aggregates after their re-hydration. Their non-cytotoxicity towards a human osteoblast cell line (MG63) was also demonstrated. The enhanced internalization of LipoParticles in this MG63 cell line, in comparison with PLGA particles, was proven by observations with a confocal laser scanning microscope, as well as by flow cytometry assays. Finally, this efficient internalization of LipoParticles in MG63 cells was confirmed by TEM on ultrathin sections, which also revealed localization close to intracellular Staphylococcus aureus.

Influence of surfactant on glass transition temperature of poly(lactic-co-glycolic acid) nanoparticles.

Poly(D,L-lactic-co-glycolic acid) (PLGA) is one of the most commonly used drug carriers in nanomedicines because of its biodegradability, biocompatibility and low toxicity. However, the physico-chemical characterization and study of drug release are often lacking the investigation of the glass transition temperature (Tg), which is an excellent indicator of drug release behavior. In addition, the residual surfactant used during the synthesis of nanoparticles will change the glass transition temperature. We thus prepared PLGA nanoparticles with polymeric (poly(vinyl alcohol) (PVA)) and ionic (didodecyldimethylammonium bromide (DMAB)) surfactant to investigate their influence on the glass transition temperature. Determination of Tg in dry and wet conditions were carried out. The use of concentrated surfactant during synthesis resulted in a larger amount of residual surfactant in the resulting particles. Increasing residual PVA content resulted in an increase in particle Tg for all but the most concentrated PVA concentrations, while increasing residual DMAB content resulted in no significant change in particle Tg. With the presence of residual surfactant, the Tg of particle and bulk samples measured in wet conditions is much lower than that in dry conditions, except for bulk PLGA containing the ionic surfactant, which may be related to the plasticizing effect of the DMAB molecules. Notably, the Tg of both particles in wet conditions is approaching physiological temperatures where subtle changes in Tg could have dramatic effects on drug release properties. In conclusion, the selection of surfactant and the remaining amount of surfactant are crucial parameters to utilize in designing the physico-chemical properties of PLGA particles.

Lectin-Modified Magnetic Nano-PLGA for Photodynamic Therapy In Vivo

The extreme aggressiveness and lethality of many cancer types appeal to the problem of the development of new-generation treatment strategies based on smart materials with a mechanism of action that differs from standard treatment approaches. The targeted delivery of nanoparticles to specific cancer cell receptors is believed to be such a strategy; however, there are no targeted nano-drugs that have successfully completed clinical trials to date. To meet the challenge, we designed an alternative way to eliminate tumors in vivo. Here, we show for the first time that the targeting of lectin-equipped polymer nanoparticles to the glycosylation profile of cancer cells, followed by photodynamic therapy (PDT), is a promising strategy for the treatment of aggressive tumors. We synthesized polymer nanoparticles loaded with magnetite and a PDT agent, IR775 dye (mPLGA/IR775). The magnetite incorporation into the PLGA particle structure allows for the quantitative tracking of their accumulation in different organs and the performing of magnetic-assisted delivery, while IR775 makes fluorescent in vivo bioimaging as well as light-induced PDT possible, thus realizing the theranostics concept. To equip PLGA nanoparticles with targeting modality, the particles were conjugated with lectins of different origins, and the flow cytometry screening revealed that the most effective candidate for breast cancer cell labeling is ConA, a lectin from Canavalia ensiformis. In vivo experiments showed that after i.v. administration, mPLGA/IR775-ConA nanoparticles efficiently accumulated in the allograft tumors under the external magnetic field; produced a bright fluorescent signal for in vivo bioimaging; and led to 100% tumor growth inhibition after the single session of PDT, even for large solid tumors of more than 200 mm3 in BALB/c mice. The obtained results indicate that the mPLGA/IR775 nanostructure has great potential to become a highly effective oncotheranostic agent.