Loaded Polymer Nanoparticles Research Articles

Mixing versus Polymer Chemistry in the Synthesis of Loaded Polymer Nanoparticles through Nanoprecipitation

Mixing versus Polymer Chemistry in the Synthesis of Loaded Polymer Nanoparticles through Nanoprecipitation

Euphorbia tirucalli latex loaded polymer nanoparticles: Synthesis, characterization, in vitro release and in vivo antinociceptive action.

The encapsulation of drugs in micro and nanocarriers has helped to resolve mechanisms of cellular resistance and decrease drug side effects as well. In this study, poly(D,L-lactide-co-glycolide) (PLGA) was used to encapsulate the Euphol active substance-containing latex from Euphorbia tirucalli (E-latex). The nanoparticles (NP) were prepared using the solvent evaporation method and the physical and chemical properties were evaluated using spectrophotometric techniques. FTIR was used to prove the formation of the ester bond between the E-latex and PLGA-NP. The UV-Vis spectroscopic technique was used to show that more than 75% of the latex was encapsulated; the same technique was used to determine the release profile of the compound at different pH values, as well as determining the speed with which the process occurs through kinetic models, and it was observed that the best adjustments occurred for the Korsmeyer-Peppas model and the Higuchi model. The DLS technique was used to determine the diameter of the particles produced as well as their zeta potential (ZP). The sizes of the particles varied from 497 to 764 nm, and it was observed that the increase in E-latex concentration causes a reduction in the diameter of the NP and an increase in the ZP (-1.44 to -22.7 mV), due to more functional groups from latex film being adsorbed to the NPs surfaces. The thermogravimetric experiments exhibit the glass transition temperatures (Tg) that is appropriate for the use of formulated NPs as a stable drug delivery device before use. The in vivo activity of E-NPs (30 and 100 mg/Kg/p.o.) was tested against carrageenan-induced mechanical hypernociception. The data demonstrated a significantly antinociceptive effect for E-NPs, suggesting that E-latex nanoencapsulation preserved its desired properties.

Functional Poly(ε-caprolactone)/Poly(ethylene glycol) Copolymers with Complex Topologies for Doxorubicin Delivery to a Proteinase-Rich Tumor Environment

Doxorubicin (DOX)-loaded polymer nanoparticles based on poly(ethylene glycol)-poly(ε-caprolactone) copolymers with a complex macromolecular topology are proposed to tackle the matrix metalloproteinase (MMP)-rich tumor environment. Linear, 4-arm comb-like copolymers and 4-arm brush block copolymers were synthesized through a combination of ring opening polymerization and atom transfer radical polymerization, in order to control the molar mass distribution, the arm/brush architecture, as well as the final size and DOX loading of self-assembled nanoparticles obtained by nanoprecipitation. The optimized nanocarriers were conjugated with penetrating low molecular weight protamine peptides coupled to a polyanionic inhibitory domain cleavable by matrix metalloproteinase-2 (MMP2). DOX-loaded, MMP2-activable nanocarriers were evaluated in the context of glioblastoma (GBM), a brain tumor characterized by remarkable and relevant MMP2 expression. Uptake and cytotoxicity in patient-derived GBM cells correlated with the level of MMP2 enzymatic activity in a dose- and time-dependent manner. No effects were observed in nontumoral endothelial cells that do not express MMP2. Results demonstrated that, by tuning polymer topology and peptide sequence, nanoparticle self-assembly, DOX encapsulation, and delivery can be optimized for the development of an advanced treatment for MMP2-overexpressing tumors.

Assembly of Fluorescent Polymer Nanoparticles Using Different Microfluidic Mixers.

Nanoprecipitation is a facile and efficient approach to the assembly of loaded polymer nanoparticles (NPs) for applications in bioimaging and targeted drug delivery. Their successful use in clinics requires reproducible and scalable synthesis, for which microfluidics appears as an attractive technique. However, in the case of nanoprecipitation, particle formation depends strongly on mixing. Here, we compare 5 different types of microfluidic mixers with respect to the formation and properties of poly(d-l-lactide-co-glycolide) (PLGA) and poly(methyl methacrylate) NPs loaded with a fluorescent dye salt: a cross-shaped mixer, a multilamination mixer, a split and recombine mixer, two herringbone mixers, and two impact jet mixers. Size and fluorescence properties of the NPs obtained with these mixers are evaluated. All mixers, except the cross-shaped one, yield NPs at least as small and fluorescent as those obtained manually. Notably in the case of impact jet mixers operated at high flow speeds, the size of the NPs could be strongly reduced from >50 nm down to <20 nm. Surprisingly, the fluorescence quantum yield of NPs obtained with these mixers also depends strongly on the flow speed, increasing, in the case of PLGA, from 30 to >70%. These results show the importance of precisely controlling the assembly conditions for loaded polymer NPs. The present work further provides guidance for choosing the optimal microfluidic setup for production of nanomaterials for biomedical applications.

Structure Inversion‐Bridged Sequential Amino Acid Metabolism Disturbance Potentiates Photodynamic‐Evoked Immunotherapy

AbstractReactive oxygen species (ROS)‐activated immunotherapy is decided by the ROS level and immunosuppressive microenvironment. This report shows the construction of indoleamine 2,3‐dioxygenase (IDO) inhibitor dimers (d‐ss‐DO)‐loaded polymer nanoparticles assembled from Ce6‐tethered disulfide bond‐bridged copolymers. The biomimetic polymeric nanoparticles can serve as glutathione peroxidase to deplete glutathione (GSH) and realize the dense‐to‐loose structure inversion (SI) arising from GSH‐triggered disulfide bonds breakage, which favors d‐ss‐DO release and GSH‐arised d‐ss‐DO cleavage into monomer. This sequential GSH metabolism disturbance can break the redox equilibrium and induce cell dyshomeostasis for facilitating more ROS accumulation and removing cancer stress protection in the photodynamic process. More significantly, the cleaved monomer modulates tryptophan (Trp) metabolism for blockading IDO immune escape target and liberating IDO‐induced immune dampening effect, which along with massively accumulated ROS, mitigates the immunosuppressive microenvironment for potentiating systematic immune responses and increasing tumor vulnerability especially after combining with anti‐PD‐L1. Thus, the SI‐bridged sequential amino acid (i.e., GSH, Trp) metabolism disturbance brings about the largest photodynamic‐evoked immunotherapeutic consequences against breast cancer and melanoma via altering the expressions of apoptosis—amino acids biosynthesis—and glycolysis/gluconeogenesis‐related genes, thus holding high potential in ROS‐activated immunotherapy.

Synthesis, self-assembly and drug release study of a new dual-responsive biocompatible block copolymer containing phenylalanine derivative

Stimuli-responsive polymers as drug delivery vehicles have generated remarkable interest among polymer researchers during the last decade. In the present work, we report the synthesis of a new water soluble pH- and thermo-responsive biocompatible block copolymer containing phenylalanine derivatives. The block copolymer formed micelle-like self-assembled nanoparticles above critical aggregation concentration, as confirmed from fluorescence spectroscopy, DLS, and AFM studies. The self-assembly behavior was dependent on the pH and temperature of the aqueous media. These self-assembled micellar nanoparticles were capable of encapsulating hydrophobic drugs as demonstrated by the significantly higher loading capacity value of Doxorubicin (DOX) compared to commonly reported values in the literature. The release of DOX from the nanoparticles was favored at lower pH and higher temperature, a condition prevalent in cancer cells. Biocompatibility of the block copolymer and the effectiveness of the nanoparticles in potential cancer therapy were established by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) studies using non-cancerous murine fibroblasts L929 cells and breast cancer cell line MDA MB 231 at 37 °C and 42 °C. The cytotoxicity of DOX loaded polymer nanoparticles was found to be more effective at 42 °C compared to 37 °C. Thus, these micellar nanoparticles hold promise in drug delivery application in cancer therapy.

Microfluidic synthesis of curcumin loaded polymer nanoparticles with tunable drug loading and pH-triggered release

Polymer nanoparticles (NPs) have attracted significant interest in the past years for drug delivery and triggered release. However, it remains a significant challenge to produce polymer NPs with controlled properties and tunable drug loading. Traditional nanoprecipitation often leads to low drug loading. This study reports the development of a new microfluidic nanoprecipitation approach for making polymer NPs with tunable drug loading up to 50%. The synthesized curcumin-loaded shellac NPs remain very stable for the period of our experiments (10 days) under acidic conditions (pH 4.5), but release the payload at neutral pH in a sustained manner. This work provides a new strategy for making drug-loaded polymer NPs with tunable drug loading and triggered release.

Dual controlled release effect of montmorillonite loaded polymer nanoparticles for ophthalmic drug delivery

Montmorillonite based polymeric nanoparticles was designed to effectively deliver adequate concentrations of drug to the ocular site after topical administration for treatment of glaucoma. In vitro and in vivo studies were carried out to evaluate their drug delivery performances. Betaxolol hydrochloride (BH) intercalated montmorillonite (Mt-BH) was successfully encapsulated into the Eudragit®PO (Mt-BH NPs) via an opportunely emulsification-solvent evaporation technique as indicated by Fourier transform infrared, differential scanning calorimentry, and the nitrogen sorption and desorption isotherms. The resulting nanoparticle system showed the mean particle diameters of 82 ± 8 nm and positive ζ potentials, with encapsulation efficiency of 77 ± 1% and drug-loading rate of 8 ± 2%. Interestingly, in vitro release profile of Mt-BH NPs exhibits an initial burst of surface-bound BH, followed by a slow release of BH due to polymer erosion, and a further drug release after the particle completely breakdown. About 80% were released after 10 h. The designed drug delivery system showed little irritation and well tolerance of nanoparticles in a chorioallantoic membrane assay. The new Eudragit®PO polymer nanoparticles system reported here is expected to be useful in ophthalmic application.

British Society for Gene and Cell Therapy Autumn Conference Friday 23 November 2018 Regent's University Conference Centre, London, UK www.bsgct.org

British Society for Gene and Cell Therapy Autumn Conference Friday 23 November 2018 Regent's University Conference Centre, London, UK www.bsgct.org

Enhanced Anti-tumor of Pep-1 Modified Superparamagnetic Iron Oxide/PTX Loaded Polymer Nanoparticles.

Superparamagnetic iron-oxide nanoparticle (SPION) has gained tremendous attention for drug delivery applications due to their unique properties. In this study, we developed a dual targeted delivery system with paclitaxel (PTX) and SPION co-loaded PLGA nanoparticles, modified with Pep-1 peptide (Pep-NP-SPION/PTX), to achieve magnetic targeting and active targeting for tumor treatment. SPION was synthesized by a co-precipitation method and was then encapsulated with PTX simultaneously into PLGA nanoparticles. After that, the non-complex was conjugated with Pep-1 through chemical modification. The resulting Pep-NP-SPION/PTX showed a spherical morphology and an average size of 100 nm. The enhancement cellular uptake of Pep-NP-SPION was demonstrated in in vitro through cell experiments. The IC50 value of Pep-NP-SPION/PTX and NP-SPION/PTX was determined to be 10.2 and 19.4 μg/mL, respectively. A biodistribution study showed that obvious higher accumulations of Pep-NP-SPION was observed in tumors, compared with that of non-targeting nanocomposites. Moreover, under the condition of a magnetic field, both NP-SPION and Pep-NP-SPION exhibited much higher tumor distribution. Furthermore, Pep-NP-SPION/PTX presented desirable in vivo anti-tumor effects based on active targeting and magnetic targeting characteristics. Altogether, Pep-NP-SPION/PTX can offer magnetic targeting and receptor mediated targeting to enhance the anti-tumor outcome.

Synthesis, Characterization and Antibacterial Activity of Ciprofl oxacin Loaded Polymer Nanoparticles for Parenteral Application

Different polymerization techniques as particle formation processes for ciprofl oxacin-loaded poly (butyl cyanoacrylate) nanoparticles (CfH-PBCN) were evaluated to choose the most appropriate in terms of the resulting nanoparticles characteristics suitable for parenteral administration.

SPIONs/DOX loaded polymer nanoparticles for MRI detection and efficient cell targeting drug delivery

Reducible polydopamine coated magnetic nanoparticles (SPIONs@PDA) for both magnetic resonance imaging (MRI) detection and cell targeting drug delivery.

Aggregation-induced emission (AIE) dye loaded polymer nanoparticles for gene silencing in pancreatic cancer and their in vitro and in vivo biocompatibility evaluation

We have developed aggregation-induced emission (AIE) dye loaded polymer nanoparticles with deep-red emission for siRNA delivery to pancreatic cancer cells. Two US Food and Drug Administration (FDA) approved surfactant polymers, Pluronics F127 and PEGylated phospholipid, were used to prepare the dye-loaded nanoparticle formulations and they can be used as nanovectors for gene silencing of mutant K-ras in pancreatic cancer cells. The successful transfection of siRNA by the developed nanovectors was confirmed by the fluorescent imaging and quantified through flow cytometry. Quantitative real time polymerase chain reaction (PCR) indicates that the expression of the mutant K-ras oncogene from the MiaPaCa-2 pancreatic cancer cells has been successfully suppressed. More importantly, our in vivo toxicity study has revealed that both the nanoparticle formulations are highly biocompatible in BALC/c mice. Overall, our results suggest that the AIE dye-loaded polymer nanoparticle formulations developed here are suitable for gene delivery and have high potential applications in translational medicine research.

Controlled release of cisplatin and cancer cell apoptosis with cisplatin encapsulated poly(lactic-co-glycolic acid) nanoparticles

The goal of the present study is to utilize cis-diamminedichloroplatinum (cisplatin) loaded polymer nanoparticles (NPs) to give a controlled, extended, and local drug therapy for the treatment of cancer. We have used biodegradable and biocompatible poly(lactic-co-glycolic acid) (PLGA) to prepare the NPs by adjusting the double emulsion technique using poly(vinylalcohol) as a surface active agent. The PLGA NPs were characterized for particle size and shape, controlled release of cisplatin, and degradation. Cisplatin solubility in deionized water was increased up to 4 mg/mL by simply changing the solution parameters. Cisplatin encapsulated NPs were incubated in phosphate buffered saline (PBS) at 37?C to study the release kinetics of cisplatin. Cisplatin was released in a sustained manner with less than 20% release during a 3-day period followed by 50% release during a 21-day period. A degradation study of PLGA NPs demonstrated the loss of spherical shape during a 21-day period. We also examined the cisplatin sensitive A2780 cell apoptosis when cells were incubated with cisplatin encapsulated PLGA NPs. A large number of cell apoptosis occurred as a result of cisplatin release from the PLGA NPs. These results suggest that cisplatin encapsulated PLGA NPs can be used to treat the cancer cells by injecting them into a localized site minimizing the side effects.

Biodegradable Amphiphilic Tri-Block Copolymeric Nanoparticles for Controlled MTB Drug Delivery

. A series of biodegradable amphiphilic tri-block copolymers (PLGA–PEG–PLGA) have been derived from the diblock copolymer poly (lactic–co–glycolic acid (PLGA)) and polyethylene glycol (PEG). The mycobacterium tuberculosis (MTB) drug pyrazinamide (PZA) loaded polymer nanoparticles (NPs) have been prepared by probe-sonication followed by w/o/w double emulsification technique. The copolymers have been characterized by FTIR and 1HNMR spectroscopic techniques, TG-DTA analysis, GPC analysis and powder XRD pattern. The MTB drug loaded polymeric NPs have been characterized by FESEM, powder XRD, HRTEM and XPS analysis. The drug loading efficiency, drug content and in vitro drug release studies have been carried out by spectrophotometry. The drug loading efficiency and drug content of triblock copolymeric NPs were higher than these of diblock copolymeric microparticles (MPs). The in vitro drug release studies indicate that the NPs exhibit initial burst release followed by controlled release of PZA for longer durations. The drug release kinetics mechanism has been evaluated by zero order, first order, Korsemeyer-Peppas (KP) and Higuchi models.

Thiolated chitosan nanoparticles as a delivery system for antisense therapy: evaluation against EGFR in T47D breast cancer cells

Thiolated chitosan has high transfection and mucoadhesive properties. We investigated the potential of two recently synthesized polymers: NAC-C (N-acetyl cysteine-chitosan) and NAP-C (N-acetyl penicillamine-chitosan) in anticancer drug delivery targeting epidermal growth factor receptor (EGFR). Doxorubicin (DOX) and antisense oligonucleotide (ASOND)-loaded polymer nanoparticles were prepared in water by a gelation process. Particle characterization, drug loading, and drug release were evaluated. To verify drug delivery efficiency in vitro experiments on a breast cancer cell line (T47D) were performed. EGFR gene and protein expression was analyzed by real time quantitative polymerase chain reaction and Western blotting, respectively. A loading percentage of 63% ± 5% for ASOND and 70% ± 5% for DOX was achieved. Drug release data after 15 hours showed that ASOND and DOX were completely released from chitosan-based particles while a lower and more sustained release of only 22% ± 8% was measured for thiolated particles. In a cytosol simulated release medium/reducing environment, such as found intracellularly, polymer-based nanoparticles dissociated, liberating approximately 50% of both active substances within 7 hours. ASOND-loaded polymer nanoparticles had higher stability and high mucoadhesive properties. The ASOND-loaded thiolated particles significantly suppressed EGFR gene expression in T47D cells compared with ASOND-loaded chitosan particles and downregulated EGFR protein expression in cells. This study could facilitate future investigations into the functionality of NAP-C and NAC-C polymers as an efficient ASOND delivery system in vitro and in vivo.