Preparation of nanoparticles by the self-organization of polymers consisting of hydrophobic and hydrophilic segments: Potential applications

This review describes the preparation of core-corona type polymeric nanoparticles and their applications in various technological and biomedical fields. Over the past two decades, we have studied the synthesis and clinical applications of core-corona polymeric nanoparticles composed of hydrophobic polystyrene and hydrophilic macromonomers. These nanoparticles were utilized as catalyst carriers, carriers for oral peptide delivery, virus capture agents, and vaccine carriers, and so on. Moreover, based on this research, we attempted to develop novel biodegradable nanoparticles composed of hydrophobic poly(γ-glutamic acid) (γ-PGA) derivatives (γ-hPGA). Various model proteins were efficiently entrapped on/into the nanoparticles under different conditions: encapsulation, covalent immobilization, and physical adsorption. The encapsulation method showed the most promising results for protein loading. It is expected that biodegradable γ-hPGA nanoparticles can encapsulate and immobilize various biomacromolecules. Nanoparticles consisting of hydrophobic and hydrophilic segments have great potential as multifunctional carriers for pharmaceutical and biomedical applications, such as drug, protein, peptide or DNA delivery systems.     

Versatile Types of Polysaccharide-Based Drug Delivery Systems: From Strategic Design to Cancer Therapy

Chemotherapy is still the most direct and effective means of cancer therapy nowadays. The proposal of drug delivery systems (DDSs) has effectively improved many shortcomings of traditional chemotherapy drugs. The technical support of DDSs lies in their excellent material properties. Polysaccharides include a series of natural polymers, such as chitosan, hyaluronic acid, and alginic acid. These polysaccharides have good biocompatibility and degradability, and they are easily chemical modified. Therefore, polysaccharides are ideal candidate materials to construct DDSs, and their clinical application prospects have been favored by researchers. On the basis of versatile types of polysaccharides, this review elaborates their applications from strategic design to cancer therapy. The construction and modification methods of polysaccharide-based DDSs are specifically explained, and the latest research progress of polysaccharide-based DDSs in cancer therapy are also summarized. The purpose of this review is to provide a reference for the design and preparation of polysaccharide-based DDSs with excellent performance.     

Techniques for the Assessment of Mucoadhesion in Drug Delivery Systems: An Overview

Abstract

In recent years mucoadhesive drug delivery systems have been developed for oral, buccal, nasal, ocular, rectal and vaginal routes for either systemic or local effects. Mucoadhesive drug delivery systems are presently being explored because of their potential advantages including increased residence time of the drug at the site of application, relatively rapid uptake of the drug into the systemic circulation, and enhanced bioavailability of the therapeutic agents. This review focuses on trends and techniques for mucoadhesion assessment which includes various experimental methods that have been used for the characterization of mucoadhesive polymers and/or delivery systems. These techniques are categorized into two methods, namely methods for mechanism assessment and methods for formulation evaluation. The techniques used to evaluate mecha nisms of mucoadhesion include atomic force microscopy, texture analysis, rheological, wetting and zeta potential measurements for the assessment of interactions between the mucoadhesive polymer/system and mucosal surface. The methods for the evaluation of mucoadhesion based formulations are also further classified as ex vivo, in vitro as well as pharmacokinetic methods. Hence, the techniques highlight the possibility of evaluating mucoadhesion phenomenon in spite of its complexity.     

Construction of pH‐Responsive Supramolecular Assemblies Based on Dynamic Covalent Bonds for Tunable Drug Release

In the present work, we propose a novel strategy for preparing supramolecular self‐assemblies for pH‐responsive drug delivery. In alkaline solutions, a novel supra‐amphiphile can be fabricated by a cationic surfactant dodecyl[2‐(4‐formylphenoxy)ethyl] dimethylammonium bromide (C₁₂‐CHO) and a drug molecule (isonicotinic acid hydrazide) via a dynamic covalent bond. The constructed supra‐amphiphile can hierarchically self‐assemble into ordered micelles, which facilitates its use for drug delivery. Interestingly, the supra‐amphiphile can facilely disassemble under specific acidic conditions, which is convenient for controlled release of drugs. Thus, this ionic amphiphile‐drug system paves a way for realizing pH‐driven targeted drug release.     

Drug and Protein Encapsulation by Emulsification: Technology Enhancement Using Foam Formulations

Significant progress has been made in developing formulations for protein and drug encapsulation and delivery. The most frequently used method is the emulsion/solvent removal technology, where microencapsulation of proteins in polymeric matrices can be easily achieved with a simple stirrer setup. However, it remains a challenge to produce protein‐encapsulated formulations with high encapsulation efficiencies. The emulsion/solvent removal technique and the relevant formulation and process parameters that govern the protein encapsulation processes are reviewed. A new encapsulation method of using foam as a delivery medium during the preparation of protein‐loaded microparticles is proposed. The foam characteristics of direct relevance to protein encapsulation are discussed. The unique properties of foam could enhance intermolecular interactions and access to internal pore surfaces, thus making them superior compared to traditional methods employing aqueous liquid phases during protein encapsulation.     

An In Vitro Experimental Approach to Study Magnetically Targeted Release of Methotrexate From Superparamagnetic Starch Nanocarriers

In the field of drug delivery, magnetic nanoparticles have great potential to modernize anticancer therapy. In the present study iron oxides containing superparamagnetic starch nanoparticles were prepared by emulsion crosslinking method. The anticancer drug methotrexate was used for loading onto the magnetic starch nanoparticles and released drug was spectrophotometrically monitored at physiological pH (7.4) under application of a modulating magnetic field. The spectroscopic techniques such as FTIR, TEM, X-ray diffraction, and vibrating sample magnetometer (VSEM) studies were used to characterize the magnetic starch nanocarriers. The influence of various experimental parameters such as pH and temperature of the release media, percent drug loading, chemical compositions of nanocarriers, and applied magnetic field were investigated on the drug release profiles of synthesized magnetic starch nanoparticles. The nanoparticles were also evaluated for cytotoxicity and in vitro blood compatibility.     

Detoxification of Polycyclic Aromatic Hydrocarbon Diol Epoxides by Human Glutathione Transferases: Efficiency of Conjugation in Intact Cells Relative to Purified Enzymes

V79MZ cells expressing human glutathione transferases (hGST) have been constructed and used to study glutathione (GSH) conjugation of anti -diol epoxides (DEs) of dibenzo[ a,l ]pyrene ( DBPDE ), and benzo[ a ]pyrene ( BPDE ). Cells expressing hGSTM1-1 were more effective with ( m )- anti - DBPDE than hGSTP1-1. The opposite was observed with (+)- anti - BPDE . Rates of cellular DE uptake and solvolysis in conjunction with oil/water partition coefficients were used to calculate the amount of DEs available for GST-catalyzed conjugation in the cells. Using this information and the known values of k cat /K M for (+)- anti - BPDE and ( m )- anti - DBPDE with purified hGSTs, it was calculated that up to 3% of available (+)- anti - BPDE forms GSH conjugates whereas the corresponding figure with the less reactive and more lipophilic ( m )- anti - DBPDE was about 19%. In part, the lower fraction of (+)- anti -BPDE conjugated in cells is probably due to rapid and competing reactions with cellular constituents.     

Characterization of Magnesium Orotate‐Loaded Chitosan Polymer Nanoparticles for a Drug Delivery System

The drug release properties of magnesium orotate (MgOr) encapsulated in the chitosan (CS) cavity and the complexation behavior between MgOr and CS were investigated. The MgOr‐loaded CS nanoparticles (MgOrCSNPs) were characterized by differential scanning calorimetry, Fourier transform infrared spectroscopy, X‐ray diffraction, transmission electron microscopy, and scanning electron microscopy with energy‐dispersive X‐ray spectroscopy. MgOr was successfully encapsulated into the CS cavity. Results with 3‐(4,5‐dimethylthiazol‐2‐yl)2,5‐diphenyl tetrazolium bromide indicated that MgOrCSNPs retained their cytotoxic activity against the liver cancer cell line (HepG2) and breast cancer cell line (MCF‐7), and low toxicity against the human cell line (3T3) and human retinal epithelial cell line (ARPE‐19).     

Electrodeposition of Cu from Acidic Sulphate Solutions in the Presence of PEG: An Electrochemical and Spectroelectrochemical Investigation – Part I

This paper deals with the effects of PEG during Cu electrodeposition from an acidic sulphate solution. This investigation was carried out with electrochemical and spectroelectrochemical techniques. Potentiostatically grown layers were examined by scanning electron microscopy. Adsorption of PEG on the growing Cu surface can be inferred from electrokinetic, SERS and morphological evidence: variations of the estimated exchange current density, qualitative and quantitative differences in the potentiostatic transients, changes on the cathodic current efficiency, effects on the three-dimensional crystallisation mode under both compact and dendritic growth conditions, appearance of surface-enhanced PEG-related Raman bands. SERS spectra revealed cathodic reactivity of adsorbed PEG.     

The Evolution of Tumor-Targeted Drug Delivery: From the EPR Effect to Nanoswimmers

Therapeutic nanotechnologies have made great progress over the past decade. Skepticism has been replaced by the understanding that precision at the nanoscale allows improved treatment modalities in humans. Principles for designing tumor-targeted drug delivery systems are described. At first, the enhanced permeability and retention (EPR) effect was the major targeting mode, with up to 10 % of the injected dose actually reaching tumors. To improve cellular uptake, sugars, antibodies, peptides or other ligands were added to the surface of nanotherapeutics. These can be coupled with external magnetic fields or ultrasonic waves to propel iron oxide or gas-filled particles towards the disease site. Next-generation drug delivery systems will be capable of autonomously swimming towards the disease site and penetrating deep tissue, independent of blood or lymphatic flow. This has been shown to some extent with modified, drug-producing, bacteria. Interestingly, sperm may be nature’s best example of a multifunctional, targeted, high-fidelity, self-propelled, delivery system that we can learn from.     

Multifunctional Nanoaggregates Composed of Active CPUL1 and a Triphenylphosphine Derivative for Mitochondria-Targeted Drug Delivery and Cell Imaging

We report that active substance (CPUL1) and triphenylphosphine (TPP) derivative could self-assemble into multifunctional nanoaggregates (CPUL1−TPP NAs) through electrostatic and π-π stacking interactions. CPUL1 was wrapped tightly inside the nanoparticles as well as CPUL1 and TPP derivative self-assembled into stable and compact nanoparticles in water. The positive surface charge of CPUL1−TPP NAs made them much easier to be endocytosed to enter cytoplasm, accumulate in the mitochondria and induce cell apoptosis based on their mitochondria targeting ability, fluorescence property and fast cell uptake characteristic, which showed better antitumor efficacy on HUH7 hepatoma cells in vitro than that of free CPUL1.     

Nanocomposites of Polymeric Biomaterials Containing Carbonate Groups: An Overview

The modification of biomaterials using nanoadditives can lead to the development of novel materials for a wide variety of biomedical applications such as drug administration systems, tissue engineering, bioresistance coatings, and biomedical instruments. Moreover, a further improvement of mechanical and thermal properties of aforementioned biomaterials while maintaining their dimensional stability is a goal of major scientific researches. Aliphatic polycarbonates (APCs) containing carbonate groups such as poly(trimethylene carbonate), poly(propylene carbonate), poly(ethylene carbonate), poly(dimethyl trimethylene carbonate), etc., have become much more interesting compared to other biodegradable materials due to their unique physical and chemical properties. This review presents the effect of applying different kinds of nanoparticles (NPs) on the mechanical, thermal, and viscoelastic properties as well as dimensional stability and biocompatibility of APCs. The dispersion process of nanofillers within polymer matrices has been divided into two groups, solution and melt mixing techniques. Moreover, synthesis procedures of APC loaded NPs for drug delivery systems and electrospinning of nanofiber mats have also been reviewed. In order to clarify the effect of NPs on the overall characteristics of the APC biomaterials, the detailed mechanism of improving process have been extensively discussed.     

Studies on fouling by natural organic matter (NOM) on polysulfone membranes: Effect of polyethylene glycol (PEG)

Polysulfone membranes were prepared via phase inversion technique by using polyethylene glycol with molecular weights of 400, 1500 and 6000 Da as pore forming agent in dope formulation. The performance of membrane was characterized using humic acid and water sample taken from Sembrong River, Johor, Malaysia was used as natural organic matter sources. Membrane properties were also characterized in terms of mean pore radius, pure water flux, humic acid rejection and fouling resistance. The results indicated that the pure water flux and mean pore radius of membranes increased with the increase of PEG content. Fourier transform infrared spectroscopy results revealed the presence of hydrophilic component in PSf/PEG blend with the significant appearance of O–H peak at 3418.78 cm^− 1. Scanning electron microscopy analysis revealed the presence of finger-like structure for all membranes and the structure intensified as PEG content was increased. The results obtained from the fouling study indicated that the membrane with the lowest PEG content and molecular weight has an excellent performance in mitigating fouling.     

Stearic Acid Modified Stearyl Alcohol Oleogel: Analysis of the Thermal,Mechanical and Drug Release Properties

The present study delineates the effect of stearic acid on the properties of stearyl alcohol oleogel. Herein, a series of oleogels were prepared by mixing different proportions of fatty alcohol (Stearyl alcohol; gelator) and fatty acid (stearic acid; co‐gelator). The characterization of the oleogels was done by thermal, macro‐scale stress relaxation, drug release, and antimicrobial studies. The oleogels were formed by the self‐assembly of stearyl alcohol/stearic acid. Thermal studies indicated that the stearic acid alters the crystal morphology, polymorphic transition and rate of crystallization of stearyl alcohol. The firmness of the oleogels with higher stearic proportion was better, which was due to the formation of a rigid network structure of stearyl alcohol in the presence of stearic acid. The release of ciprofloxacin hydrochloride, model drug, from the oleogels was better from the oleogels with higher stearic acid content. The release of the drug from the oleogels was Fickian diffusion‐mediated; except the oleogel with the highest stearic acid proportion. The antimicrobial study showed that the drug loaded oleogels were able to resist the growth of Escherichia coli, model microbe.     

Synthesis of biocompatible dendrimers with a peripheral network formed by linking of polymerizable groups

Toward the production of unimolecular nanocapsules with biocompatible surface, we prepared a fourth generation polyamidoamine dendrimer having both a poly(ethylene glycol) (PEG) with the number average molecular weight of 2000 and a methacryloyl group at every chain end of the dendrimer through an l-lysine residue. The introduced methacryloyl groups of the dendrimer were successfully polymerized by using free radical initiators, such as azobisisobutyronitrile and dibenzoyl peroxide, as judged by ¹H NMR. GPC revealed that the molecular weight of the dendrimers having the polymerizable groups did not change after their polymerization, indicating that the polymerization of the methacryloyl groups took place within the single dendrimer. Polymerization of the methacryloyl groups resulted in a significant reduction of the affinity of the dendrimer to a guest molecule, rose bengal, suggesting that the peripheral network formed by the linking of methacryloyl groups hides the dendrimer interior. In addition, when the methacryloyl groups of the dendrimer were polymerized in the presence of rose bengal, the guest molecule was found to be tightly associated with the dendrimer.     

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.     

Enlargement of Nanoemulsion Region in Pseudo-ternary Mixing Diagrams for a Drug Delivery System

The purpose of this research was to develop the pseudo-ternary mixing diagrams for a potential drug delivery system consisting of vitamin E (potential drug) + soybean oil + surfactant + co-surfactant (anhydrous glycerol) + water. The potential drug (vitamin E) was loaded in the oil phase. The effects of different surfactants (pure and mixed) on the mixing diagrams, especially on the nanoemulsion region, were investigated. The influence of the drug loading level on the mixing diagrams was also determined. The surfactants studied were polyethoxylated (20) sorbitan monolaurate, polyethoxylated (20) sorbitan monooleate, polyethoxylated (35) castor oil and their mixtures. The size (area) of the nanoemulsion region of the mixing diagrams was found to be dependent on the type of surfactant used and the loading level of the drug (vitamin E).     

Fabrication and biomedical potential of nanogels: An overview

Nanogels are one of the innovative hydrogel systems that comprise cross-linked polymers of natural or synthetic origin having good water holding capacity. The hydrophilic nature of nanogels possess good water uptake and exhibit controlled, targeted and sustained release. Nanogels show promising features like high biodegradability, biocompatibility, drug loading capacity and good penetration power. This overview mainly focuses on the biomedical applications of nanogels as the drug delivery system, imaging agent, therapeutic carrier, theranostic agent, also its fabrication techniques. In current scenario, nanogels play promising roles to deliver drugs such as anticancer, autoimmune, ophthalmics, anti-microbials, anti-inflammatory, proteins and peptides.     

Overview of preparation methods of polymeric and lipid-based (niosome,solid lipid,liposome) nanoparticles: A comprehensive review

A wide number of drug nanocarriers have emerged to improve medical therapies, and in particular to achieve controlled delivery of drugs, genes or gene expression-modifying compounds, or vaccine antigens to a specific target site. Of the nanocarriers, lipid-based and polymeric nanoparticles are the most widely used. Lipid-based systems like niosomes and liposomes are non-toxic self-assembly vesicles with an unilamellar or multilamellar structure, which can encapsulate hydrophobic/hydrophilic therapeutic agents. Polymeric nanoparticles, usually applied as micelles, are colloidal carriers composed of biodegradable polymers. Characteristics such as loading capacity, drug release rate, physical and chemical stability, and vesicle size are highly dependent on experimental conditions, and material and method choices at the time of preparation. To be able to develop effective methods for large scale production and to meet the regulatory requirements for eventual clinical implementation of nanocarriers, one needs to have in-depth knowledge of the principles of nanoparticle preparation. This review paper presents an overview of different preparation methods of polymeric and novel lipid-based (niosome and solid lipid) nanoparticles.     

Dissolution enhancement of flavonoids by solid dispersion in PVP and PEG matrixes: A comparative study

Polyvinylpyrrolidone (PVP) and poly(ethylene glycol) (PEG) solid dispersion systems with flavanone glycosides, naringin and hesperidin, and their aglycones, naringenin and hesperetin, were prepared, using solvent evaporation method, to enhance their dissolution rates that may affect their bioavailability. Drug release of both flavanone glycosides and their aglycones was directly affected by the physical state of solid dispersions. Powder‐XRD technique in combination with scanning and transmission electron microscopy revealed that PVP polymer formed amorphous nanodispersion systems with flavanone aglycones, while such systems could not be formed with their glycosides, which are bulkier molecules. Fourier transform infrared spectra suggest the presence of hydrogen bonds between PVP carbonyl groups and hydroxyl groups of both flavanone aglycones. These interactions prevent the crystallization of naringenin and hesperetin aglycones in PVP matrix. On the other hand, the ability of PEG carrier to form hydrogen bonds with flavanone glycosides or aglycones was limited, and as a result both flavanone glycosides and their aglycones remain in the crystalline form. For this reason, the solubility enhancement of PEG solid dispersions was lower than when PVP was used as drug carrier. At pH 6.8, the % release of naringenin and hesperetin from PVP/naringenin–hesperetin (80/20 w/w) solid dispersion was 100% while in PEG solid dispersions, it was not higher than 60–70%. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 102: 460–471, 2006