A comparative in vitro evaluation of self-assembled PTX-PLA and PTX-MPEG-PLA nanoparticles

We present a dialysis technique to direct the self-assembly of paclitaxel (PTX)-loaded nanoparticles (NPs) using methoxypolyethylene glycol-poly(d,l-lactide) (MPEG-PLA) and PLA, respectively. The composition, morphology, particle size and zeta potential, drug loading content, and drug encapsulation efficiency of both PTX-PLA NPs and PTX-MPEG-PLA NPs were characterized by X-ray diffraction, Fourier transform infrared spectroscopy, transmission electron microscopy, dynamic light scattering, electrophoretic light scattering, and high-performance liquid chromatography. The passive targeting effect and in vitro cell viability of the PTX-MPEG-PLA NPs on HeLa cells were demonstrated by comparative cellular uptake and MTT assay of the PTX-PLA NPs. The results showed that the PTX-MPEG-PLA NPs and PTX-PLA NPs presented a hydrodynamic particle size of 179.5 and 441.9 nm, with a polydispersity index of 0.172 and 0.189, a zeta potential of −24.3 and −42.0 mV, drug encapsulation efficiency of 18.3% and 20.0%, and drug-loaded content of 1.83% and 2.00%, respectively. The PTX-MPEG-PLA NPs presented faster release rate with minor initial burst compared to the PTX-PLA NPs. The PTX-MPEG-PLA NPs presented superior cell cytotoxicity and excellent cellular uptake compared to the PTX-PLA NPs. These results suggested that the PTX-MPEG-PLA NPs presented more desirable characteristics for sustained drug delivery compared to PTX-PLA NPs.     

Validation of a Janus role of methotrexate-based PEGylated chitosan nanoparticles in vitro

Recently, methotrexate (MTX) has been used to target to folate (FA) receptor-overexpressing cancer cells for targeted drug delivery. However, the systematic evaluation of MTX as a Janus-like agent has not been reported before. Here, we explored the validity of using MTX playing an early-phase cancer-specific targeting ligand cooperated with a late-phase therapeutic anticancer agent based on the PEGylated chitosan (CS) nanoparticles (NPs) as drug carriers. Some advantages of these nanoscaled drug delivery systems are as follows: (1) the NPs can ensure minimal premature release of MTX at off-target site to reduce the side effects to normal tissue; (2) MTX can function as a targeting ligand at target site prior to cellular uptake; and (3) once internalized by the target cell, the NPs can function as a prodrug formulation, releasing biologically active MTX inside the cells. The (MTX + PEG)-CS-NPs presented a sustained/proteases-mediated drug release. More importantly, compared with the PEG-CS-NPs and (FA + PEG)-CS-NPs, the (MTX + PEG)-CS-NPs showed a greater cellular uptake. Furthermore, the (MTX + PEG)-CS-NPs demonstrated a superior cytotoxicity compare to the free MTX. Our findings therefore validated that the MTX-loaded PEGylated CS-NPs can simultaneously target and treat FA receptor-overexpressing cancer cells.     

Recent advances in systemic and local delivery of ginsenosides using nanoparticles and nanofibers

Ginsenosides are the main pharmacologically active constituents of ginseng which have been used in East Asian countries for centuries to modulate blood pressure, metabolism and immune function. Following the technological advances in isolation, purification and mass production, their mechanisms of action are gradually elucidated, providing solid basis for clinical applications. Ginseng extracts (total ginsenosides) and ginsenoside Rg3, CK, Rd have been marketed or entered clinical trials as drugs or dietary supplements. Despite the proven safety and efficacy of some ginsenosides, their applications are hindered by inferior pharmacokinetics such as low solubility, poor membrane permeability and metabolic instability. Nanoparticle formulation of drugs and implantable drug depots are effective strategies to improve the pharmacokinetics of therapeutic agents by enhancing solubility, providing protection, facilitating intracellular transport, and enabling sustained and controlled release. This mini-review summarizes the recent advances in systemic delivery of ginsenosides using liposomes, micelles, albumin-based nanoparticles, and inorganic nanoparticles, as well as local delivery of ginsenosides by electronspun fibrous membranes and hydrogels.     

Composite nanofibers of conducting polymers and hydrophobic insulating polymers: Preparation and sensing applications

Various conducting polymer/hydrophobic insulating polymer (CP/HIP) composite nanofibers have been prepared by electrospinning and vapor deposition polymerization (VDP) with benzoyl peroxide (BPO) as oxidant. BPO is soluble in N,N-dimethylformamide (DMF) and can form homogenous solutions with hydrophobic polymers such as poly(methyl methacrylate) (PMMA) and polystyrene (PS). High-quality nanofibers of PMMA or PS containing a certain amount of BPO were produced by electrospinning and used as the templates for VDP of pyrrole, 3,4-ethylenedioxythiophene (EDOT), and aniline. The non-woven mats of the resulting CP/HIP composite fibers can be used as the high-sensitive sensing elements of gas sensors. A gas senor based on polypyrrole (PPy)/PMMA composite fibers was fabricated for sensing ammonia or chloroform vapor, and exhibited greatly improved performances comparing with those of the device based on a PPy flat film.     

Morphology modulation of polymeric assemblies by guest drug molecules: TEM study and compatibility evaluation

Amphiphilic copolymers with poly(N-isopropylacrylamide) and ethyl tryptophan, ethyl 4-aminobenzoate, or ethyl glycinate as side groups were synthesized. Assemblies based on these copolymers were employed as model systems to investigate the morphology transformation upon loading of various hydrophobic drugs. TEM observation suggested that the loading of non-steroidal anti-inflammatory drugs, including ibuprofen, ketoprofen, indomethacin, naproxen and mefenamic acid, can trigger a significant morphological transformation of assemblies based on copolymers with low substitution of hydrophobic group. On the other hand, the introduction of steroidal anti-inflammatory drugs (medroxyprogesterone acetate, prednisone acetate and dexamethasone) and aliphatic acids (caprylic acid, tetradecanoic acid and stearic acid) has no significant effect on the morphology of assemblies derived from the same copolymers, although they do have some effect on the morphology of assemblies based on copolymers with high content of hydrophobic group. In addition, the morphology of assemblies is well correlated with drug loading efficiency. An occurrence of morphology transformation means a higher drug loading, and vice versa. Various physicochemical parameters including partition coefficient, molecular volume and solubility parameters were calculated according to group contribution method. Analysis of these data pointed to the fact that a combination of molecular volume and solubility parameters can be used as a measure to judge whether one molecule is ‘active’ or ‘neutral’. This rule can also be applied to evaluate the compatibility between candidate drugs and nanocarriers based on these copolymers.     

Preparation and structure characterization of hairy nanoparticles consisting of hydrophobic core and thermosensitive hairs

Structural characterization of hairy nanoparticles consisting of poly(styrene-co-glycidyl methacrylate) (St/GMA) core and poly(NIPA-co-vinylimidazole) (NIPA/VIm) hair has been carried out by dynamic light scattering. The hairy molecules were introduced by surface graft-polymerization of a mixture of NIPA and VIm monomers to the St/GMA core particles with the hydrodynamic radius R_H of 135±10 nm. The R_H of St/GMA-core-NIPA/VIm-hair particles was R_H=360±20 nm at 20 °C, which gradually decreased to 285±10 nm by heating to 33.0 °C, and then underwent a sharp decrease to 175±10 nm by further heating to 33.8 °C. The final value went to 159±10 nm at 36 °C. This decrease in R_H is due to the shrinking transition of NIPA/VIm chain by hydrophobic association. The degree of shrinking of the hairy particles is compared with that of bulk NIPA gels from the viewpoint of geometrical constraints.     

Comparative studies of salinomycin-loaded nanoparticles prepared by nanoprecipitation and single emulsion method

To establish a satisfactory delivery system for the delivery of salinomycin (Sal), a novel, selective cancer stem cell inhibitor with prominent toxicity, gelatinase-responsive core-shell nanoparticles (NPs), were prepared by nanoprecipitation method (NR-NPs) and single emulsion method (SE-NPs). The gelatinase-responsive copolymer was prepared by carboxylation and double amination method. We studied the stability of NPs prepared by nanoprecipitation method with different proportions of F68 in aqueous phase to determine the best proportion used in our study. Then, the NPs were prepared by nanoprecipitation method with the best proportion of F68 and single emulsion method, and their physiochemical traits including morphology, particle size, zeta potential, drug loading content, stability, and in vitro release profiles were studied. The SE-NPs showed significant differences in particle size, drug loading content, stability, and in vitro release profiles compared to NR-NPs. The SE-NPs presented higher drug entrapment efficiency and superior stability than the NR-NPs. The drug release rate of SE-NPs was more sustainable than that of the NR-NPs, and in vivo experiment indicated that NPs could prominently reduce the toxicity of Sal. Our study demonstrates that the SE-NPs could be a satisfactory method for the preparation of gelatinase-responsive NPs for intelligent delivery of Sal.     

Controlled co‐delivery of hydrophilic and hydrophobic drugs from thermosensitive and crystallizable copolymer nanoparticles

Functionalized amphiphilic block copolymers poly(N‐isopropyl acrylamide)‐b‐poly(stearyl methacrylate) (PNIPAM‐PSMA) are synthesized. Their self‐assembled core‐shell nanoparticles have the hydrophilic thermosensitive shell and hydrophobic crystallizable core. Nanoparticles exhibit volume phase transition at temperature of 38 °C and its poly(stearyl methacrylate) (PSMA) moiety could form nano size crystals to retain drugs, making them good carriers for drug co‐delivery system. Thermosensitivity and crystallinity of nanoparticles are characterized with dynamic light scattering (DLS), differential scanning calorimetry (DSC), small‐angle X‐ray scattering (SAXS), and atomic force microscopy (AFM). The interactions and relationship between chemical structures of copolymer nanoparticles and loading drugs are discussed. Different loading techniques and combined loading of hydrophobic/hydrophilic drugs are studied. Nanoparticles show a good and controllable drug loading capacity (DL) of hydrophilic/hydrophobic drugs. The drugs release kinetics is analyzed with Fick's law and Weibull model. A general method for analyzing drug release kinetics from nanoparticles is proposed. Weibull model is well fitted and the parameters with definite physical meaning are analyzed. PNIPAM‐PSMA nanoparticles show a quite different thermal response, temporal regulation, and sustained release effect of hydrophilic and hydrophobic drugs, suggesting a promising application in extended and controlled co‐delivery system of multi‐drug. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 44132.     

Preparation of polymer nanoparticles loaded with doxorubicin for controlled drug delivery

The preparation of polymer nanoparticles loaded with an active principle, commonly used in cancer treatment, is investigated here from the experimental point of view. The main novelty of this work stands in the use of continuous confined impinging jets mixers in combination with realistic materials, notably the biodegradable and biocompatible copolymer poly(methoxypolyethyleneglycolcyanoacrylate-co-hexadecylcyanoacrylate) together with two forms of the drug doxorubicin. To our knowledge this is the first attempt to use for such a system a device that can be operated continuously and can be easily scaled up. Nanoparticles are produced via solvent-displacement experimenting different solvents; the effect of the other operating parameters is also investigated. Nanoparticles are characterized in terms of their size distribution and surface properties; for a limited number of samples prepared with the optimized preparation protocol further characterization (in terms of drug loading, incorporation and release profiles) is also carried out. Collected results show that the overall approach is capable of producing nanoparticles with controlled particle size distribution, drug loading and good reproducibility and that on the contrary of what reported in the literature the presence of the active principle does play an important role.     

Removal of oil by gelation using hydrophobic silica nanoparticles

Silica nanoparticles are coated by polydimethysiloxane (PDMS) thin film using chemical vapor deposition and the PDMS-coated silica nanoparticles are shown to be highly hydrophobic. These PDMS-coated silica nanoparticles are used for selectively gelating oils in the oil/water mixture, allowing easy separation and removal of oil from water. Hydrophobized silica nanoparticles are shown to be able to gelate rotary pump oil with its mass 15 times higher than that of silica. A gelated mixture of oil and hydrophobized silica is stable and not dispersed in water for 7 days.     

Pharmapolymers in the 21st century: Synthetic polymers in drug delivery applications

The administration of drugs, as a main challenge of pharmaceutical and medicinal applications, has certainly benefited from the application of synthetic polymers. However, despite an enormous effort to develop new materials for drug delivery applications, only few of them have entered the market due to the hurdles of regulation, production, cost efficiency and both industrial’s and patients’ acceptance. In this review, we summarize all these classes of synthetic polymers, which are on the market as well as the latest developments in clinical trials, and describe their application in polymer-drug conjugates, as excipients, in nano-/microscopic and macroscopic drug carriers, as polymeric coatings, or as polymeric drugs. Our intention is to create a link between the underlying chemical structures, the properties of the polymers, and their area of application, where they are often just known by their trade names or abbreviations. In addition selected types of synthetic polymers are highlighted that feature interesting properties and have the potential to make it to the market in future.     

Computer simulations and in vivo convection-enhanced delivery of fluorescent nanoparticles demonstrate variable distribution geometry

ObjectiveConvection-enhanced delivery (CED) has emerged as a promising technique for bypassing the blood–brain barrier to deliver therapeutic agents. However, animal studies and clinical trials that utilize the technique suggest that it may require further optimization before it can be safely used in humans. In particular, while volume of distribution in the target tissue can be controlled, the geometrical spread into a desired target region is highly variable from experiment to experiment. In the present paper we have sought to characterize the non-uniform distribution geometry using fluorescent nanoparticles in both a rat model and computer simulations.MethodsUsing diffusion tensor imaging MRI data of the rat brain, we performed computer simulations of a 0.5 μL/min CED infusion. A step design catheter targeting the striatum was simulated to infuse 20 μL of infusate. Using the same infusion parameters, we then performed in vivo CED experiments where we infused fluorescently labeled polyethylene glycol-polylactide-polycaprolactone nanoparticles (FPNPs) into the rat striatum. Fluorescence microscopy was used to examine the distribution geometry histologically.ResultsThe computer simulations demonstrated large variations in distribution patterns when catheter placement was shifted by only 1 mm. Animal infusions also exhibited highly irregular and variable distribution geometries despite the use of relatively small flow rates.ConclusionComputer simulations and repeated in vivo infusions demonstrate the difficulty of achieving desired drug distribution in target tissue. We have proposed a calculation for sphericity which, along with the ubiquitous volume of distribution measure, may prove helpful in describing distribution geometry. Taken together, our results suggest that CED's limitations must be considered and further optimization may be required before the technique sees widespread use in humans.     

The use of polymer-based nanoparticles and nanostructured materials in treatment and diagnosis of cardiovascular diseases: Recent advances and emerging designs

This review summarizes important advances in polymer-based nanotechnologies for the treatment and diagnosis of cardiovascular diseases, focusing on nanoparticles and nanostructured materials/devices. The current state of the art and design parameters are discussed with the aim of providing a source of information that can aid in the development of new treatments by bridging between materials development, preclinical, and clinical trials. This is highly relevant as cardiovascular diseases remain a leading cause of death worldwide and as current treatments burden the healthcare systems with great costs. Different strategies, from targeting theranostic nanocarriers, to dual-drug depot systems, injectable cell scaffolds, and LDL acceptors are treated. The review ends with a concluding outlook on the possibilities and challenges presented to polymer-based nanotechnologies in cardiovascular disease therapy.     

Paclitaxel-loaded nanoparticles of star-shaped cholic acid-core PLA-TPGS copolymer for breast cancer treatment

A system of novel nanoparticles of star-shaped cholic acid-core polylactide-d-α-tocopheryl polyethylene glycol 1000 succinate (CA-PLA-TPGS) block copolymer was developed for paclitaxel delivery for breast cancer treatment, which demonstrated superior in vitro and in vivo performance in comparison with paclitaxel-loaded poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles and linear PLA-TPGS nanoparticles. The paclitaxel- or couramin 6-loaded nanoparticles were fabricated by a modified nanoprecipitation method and then characterized in terms of size, surface charge, surface morphology, drug encapsulation efficiency, and in vitro drug release. The CA-PLA-TPGS nanoparticles were found to be spherical in shape with an average size of around 120 nm. The nanoparticles were found to be stable, showing no change in the particle size and surface charge during 90-day storage of the aqueous solution. The release profiles of the paclitaxel-loaded nanoparticles exhibited typically biphasic release patterns. The results also showed that the CA-PLA-TPGS nanoparticles have higher antitumor efficacy than the PLA-TPGS nanoparticles and PLGA nanoparticles in vitro and in vivo. In conclusion, such nanoparticles of star-shaped cholic acid-core PLA-TPGS block copolymer could be considered as a potentially promising and effective strategy for breast cancer treatment.     

Interests of chitosan nanoparticles ionically cross-linked with tripolyphosphate for biomedical applications

The process of ionic gelation is one of the easiest ways to develop chitosan nanoparticles reported so far in the literature. Its success is mainly due to its one-shot synthesis, and to the mild environment required to produce the nanoparticles. The nanoparticle formation all along this process has been therefore thoroughly studied to lead to particles with a nanometric size, a narrow size distribution, and a spherical shape that are ideal for biomedical uses. The purpose of this review is to compile the biomedical applications that have been considered in the literature for these chitosan nanoparticles prepared by ionic gelation using tripolyphosphate as ionic agent. Their intrinsic biological properties such as non-toxicity, antimicrobial activity, mucoadhesivity and haemocompatibility are firstly discussed and compared to those of chitosan solutions. Then, the different bioactive species (drugs and biomacromolecules) incorporated in these chitosan nanoparticles, their maximal incorporation efficiency, their loading capacity, and their principal associated biomedical applications are presented.     

Preparation of hollow magnetite microspheres and their applications as drugs carriers

ABSTRACT: Hollow magnetite microspheres have been synthesized by a simple process through a template-free hydrothermal approach. Hollow microspheres were surface modified by coating with a silica nanolayer. Pristine and modified hollow microparticles were characterized by field-emission electron microscopy, transmission electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy, FT-IR and Raman spectroscopy, and VSM magnetometry. The potential application of the modified hollow magnetite microspheres as a drug carrier was evaluated by using Rhodamine B and methotrexate as model drugs. The loading and release kinetics of both molecules showed a clear pH and temperature dependent profile. GRAPHICAL ABSTRACT: Hollow magnetite microspheres have been synthesized. Load-release experiments with Rhodamine-B as a model drug and with Methotrexate (chemotherapy drug used in treating certain types of cancer) demonstrated the potential applications of these nanostructures in biomedical applications.     

Paclitaxel-incorporated nanoparticles using block copolymers composed of poly(ethylene glycol)/poly(3-hydroxyoctanoate)

Block copolymers composed of poly(3-hydroxyoctanoate) (PHO) and methoxy poly(ethylene glycol) (PEG) were synthesized to prepare paclitaxel-incorporated nanoparticle for antitumor drug delivery. In a ¹H-NMR study, chemical structures of PHO/PEG block copolymers were confirmed and their molecular weight (M.W.) was analyzed with gel permeation chromatography (GPC). Paclitaxel as a model anticancer drug was incorporated into the nanoparticles of PHO/PEG block copolymer. They have spherical shapes and their particle sizes were less than 100 nm. In a ¹H-NMR study in D₂O, specific peaks of PEG solely appeared while peaks of PHO disappeared, indicating that nanoparticles have core-shell structures. The higher M.W. of PEG decreased loading efficiency and particle size. The higher drug feeding increased drug contents and average size of nanoparticles. In the drug release study, the higher M.W. of PEG block induced the acceleration of drug release rate. The increase in drug contents induced the slow release rate of drug. In an antitumor activity study in vitro, paclitaxel nanoparticles have practically similar anti-proliferation activity against HCT116 human colon carcinoma cells. In an in vivo animal study using HCT116 colon carcinoma cell-bearing mice, paclitaxel nanoparticles have enhanced antitumor activity compared to paclitaxel itself. Therefore, paclitaxel-incorporated nanoparticles of PHO/PEG block copolymer are a promising vehicle for antitumor drug delivery.     

Light-induced release of molecules from polymers

The release of molecules from polymers upon light stimulus has been investigated for a range of applications in particular for drug delivery. In this review, the concept of light-induced release processes from polymers is summarized. Light-triggered processes can be divided into two approaches, the light induced degradation of polymers and the light-induced polarity change of the polymers. Functional groups that can enable the breakdown of the polymer or the cleavage of a linker between polymer and small molecule encompass coumarine and o-nitrobenzyl groups while azobenze and spyropyrane undergo reversible changes. Although the literature is dominated by these four compound classes, functional groups such as anthracene, pyrene, perylene, 2-diazo-1,2-naphthoquinone, and BODIPY can undergo similar changes. Degradation of polymers or simple polarity changes can trigger the release of small molecules such as drugs, but also gas molecules such as nitric oxide and macromolecules including DNA and proteins can be liberated upon light-trigger.     

Preparation and characterization of monoclinic sulfur nanoparticles by water-in-oil microemulsions technique

Nanosized monoclinic sulfur particles have been successfully prepared via the chemical reaction between sodium polysulfide and hydrochloric acid in a reverse microemulsions system, with theolin, butanol, and a mixture of Span80 and Tween80 (weight ratio 8 : 1) as the oil phase, co-surfactant and surfactant, respectively. Transparent microemulsions were obtained by mixing the oil phase, surfactant, co-surfactant, and the aqueous phase in appropriate proportion using an emulsification machine at the room temperature. The resulting sulfur nanoparticles were characterized by dynamic light scattering (DLS), X-ray diffraction (XRD), infrared spectroscopy (IR) and transmission electron microscopy (TEM).