A nanoparticulate raloxifene delivery system based on biodegradable carboxylated polyurethane: Design,optimization, characterization,and in vitro evaluation

Biodegradable carboxylated polyurethanes with three molecular weights were synthesized to prepare a nanoparticulate sustained delivery system of raloxifene hydrochloride, the drug with poor bioavailability. The nanoparticles were prepared by coprecipitation method. Optimal conditions for the preparation of nanoparticles were obtained using Box–Behnken design. Independent factors were ratio of polymer to drug, M_w of polymer and speed of magnetic stirrer. Dependent variables include zeta potential, polydispersity index (PdI), particle size, and loading efficacy (LE). Results of the fractional factorial design based on an analysis of variance demonstrated that the model for particle size, zeta potential, PdI and loading efficacy was statistically significant. The size of nanoparticles in design experiments were 46–96 nm in diameter and had entrapment efficiency of 84–92%. The nanoparticles were evaluated for in vitro release and showed a sustained release profile (24.19% ± 4.35% after 4 weeks), following the Fickian diffusion‐based release mechanism. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 39668.     

Valproate‐Loaded hydrogel nanoparticles: Preparation and characterization

Developing a simple and efficient approach to formulate biodegradable nanoparticles for intravenous delivery of sodium valproate (a hydrophilic small molecule drug chronically used in epileptic patients), is the principal objective of the current study. To fabricate particles via ionotropic gelation approach, a polycation polymer (chitosan) along with a polyanion (tripolyphosphate) was utilized in the presence of sodium valproate, and the Taguchi experimental design method was drawn upon so as to determine the optimum conditions of nanoparticle generation. In the following step, the researchers investigated sodium valproate‐loaded nanoparticles to explore various features of the nanoparticles including drug loading parameters, particle size distribution, zeta‐potential, morphology, stability, yield, and in vitro drug release profile. Nanoparticles with sizes of 63 ± 1 nm (number‐based) and 79 ± 3.21 (volume‐based) were obtained with slightly negative zeta–potential, which was more positive in drug‐loaded nanoparticles than the unloaded ones. The TEM imaging of the hydrogel nanoparticles manifested spherical shapes and corroborated the size achieved via particle size analyzer. The loading efficiency, loading amount, and loading ratio were determined to be 21.81 ± 3.90%, 10.31 ± 1.82 (mg sodium valproate/g nanoparticle) and 23.70 ± 4.54%, respectively, in optimum conditions. Moreover, there was observed a gradual drug release for nearly a week consisting, in average, about 94.64 ± 2.71% of the nanoparticles' drug content. In a nutshell, the present study introduces a practical, simple, and effective ionotropic gelation approach to generate sodium valproate‐loaded nanoparticles, leaving open a window of promising prospects in the field of intravenous long‐term delivery of this chronically used drug. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Fabrication of polymeric nanoparticles of poly(ethylene‐co‐vinyl acetate) coated with chitosan for pulmonary delivery of carvedilol

Carvedilol is a drug with low oral bioavailability due to its high first‐pass metabolism. The purpose of the present study was to prepare a mucoadhesive dry powder inhaler of this drug loaded in poly(ethylene‐co‐vinyl acetate)(PEVA) nanoparticles for pulmonary delivery. PEVA nanoparticles were prepared by an O/W solvent evaporation method and coated with different concentrations of chitosan as a mucoadhesive polymer. Encapsulation efficiency, particle size, zeta potential, release efficiency, and mucoadhesive properties of the different formulations were evaluated on mucin substrate. The optimized formulation of nanoparticles was spray dried using lactose and mannitol as carrier powders. The flowability of the obtained powders was checked by Carr's Index and Hausner ratio and the in vitro deposition of the aerosolized drug was investigated using a Next Generation Impactor. Increasing in the particle size and zeta potential of nanoparticles confirmed the settling of the chitosan coating layer on the surface of nanoparticles. The in vitro drug release from coated nanoparticles decreased with increasing of chitosan concentration. Mucoadhesive property of chitosan‐coated PEVA nanoparticles was higher than noncoated ones. Spray‐dried powders had different aerosilization behavior. Mannitol‐based formulation was found to have low density, better flow ability, smaller aerodynamic diameter (d_aer) and higher fine powder fraction. The results of the present study allow concluding that mannitol spray dried, mucoadhesive nanoparticles of PEVA are suitable inhaler powder for pulmonary delivery of carvedilol. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 39694.     

Design and optimization of alginate−chitosan−pluronic nanoparticles as a novel meloxicam drug delivery system

The inflammation and pain associated with osteoarthritis are treated with nonsteroidal anti‐inflammatory drugs (NSAIDs). This treatment is accompanied by several side effects; therefore local intra articular (IA) NSAID injection can be more efficient and safe than systemic administration or topical use. In this study, alginate?chitosan?pluronic nanoparticles were considered as a new vehicle for IA meloxicam delivery. These novel nanoparticles were prepared using an ionotropic gelation method and were optimized for variables such as alginate to chitosan mass ratio, pluronic concentration, and meloxicam concentration using a 3‐factor in 3‐level Box‐Behnken design. To optimize the formulation, the dependent variables considered were particle size, zeta potential, entrapment efficiency, and mean dissolution time (MDT). The nanoparticles morphology was characterized by FESEM and AFM. The potential interactions of the drug‐polymers were investigated by ATR‐FTIR and DSC, and the delivery profile of meloxicam from the nanoparticles was obtained. The average particle size of the optimized nanoparticles was 283 nm, the zeta potential was ?16.9 mV, the meloxicam entrapment efficiency was 55%, and the MDT was 8.9 hours. The cumulative released meloxicam amount from the composite nanoparticles was 85% at pH 7.4 within 96 h. The release profile showed an initial burst release followed by a sustained release phase. The release mechanism was non‐Fickian diffusion. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42241.     

Encapsulation of curcumin by methoxy poly(ethylene glycol‐b‐aromatic anhydride) micelles

Suitable carrier systems for sustained release of curcumin were studied by using the self‐assembled polymeric micelles. Poly(ethylene glycol) methyl ether and poly(aromatic anhydride) were used as the hydrophilic and hydrophobic blocks, respectively, in forming amphiphilic diblock copolymers. Four different types of polymers methoxy poly(ethylene glycol‐ b‐1,3‐bis(p‐carboxyphenoxy)propane) (mPEG₅₀₀₀CPP, mPEG₂₀₀₀CPP), methoxy poly(ethylene glycol‐b‐1,6‐bis(p‐carboxyphenoxy)hexane) (mPEG₅₀₀₀CPH, mPEG₂₀₀₀CPH) were synthesized via melt condensation approach. Micelles were formed at very low polymer concentration with stable hydrophobic cores. The particle sizes of micelles remained stable during degradation period. All four different polymeric micelles showed low cytotoxicity toward human fibroblasts cells and can kill cancer cells in very low concentrations. High loading efficiency and drug content were observed in curcumin‐loaded micelles. Curcumin showed mild initial burst (30% of drug loading in the first 24 h) when released from the micelles and its release was sustained for at least 18 days. These micelles, especially those of mPEG₅₀₀₀CPP, show potential to serve as the delivery vehicles for sustained release of curcumin. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011.     

Thermosensitive folic acid-targeted poly (ethylene-<Emphasis Type="Italic">co</Emphasis>-vinyl alcohol) hemisuccinate polymeric nanoparticles for delivery of epirubicin to breast cancer cells

A novel thermosensitive folic acid (FA)-targeted succinylated poly (ethylene-co-vinyl alcohol) (EVOH) (EVOHS-FA) nanocarrier was synthesized for the specific delivery of epirubicin (EPI) to MCF-7 breast cancer cell line. Three different ratios of synthesized EVOH-Suc were reacted with FA. The structure of the desired products (EVOHS₄₀-FA, EVOHS₆₀-FA and EVOHS₈₀-FA) was confirmed by ¹H NMR and FTIR techniques. Nanoparticles were obtained by nano-precipitation procedure using DMSO/H₂O as solvent/anti-solvent. The particle size, zeta potential, entrapment efficacy and in vitro release profile of the final formulations in different temperatures were measured. The optimized nanoparticles had the particle size of 214 ± 8.5 nm, zeta potential of ?29.6 mV, PDI of 0.198 ± 0.04, and a high encapsulation efficiency that released the drug efficiently within 450 h at the temperature of 40 °C compared to 37 °C. The morphology of nanoparticles was studied by scanning electron microscopy. The in vitro cytotoxicity was evaluated using the MTT assay on MCF-7 cell lines in response to temperatures of 37 and 40 °C. The MTT assay indicated that the targeted nanoparticles carrying EPI were significantly more cytotoxic than the non-targeted nanoparticles and the free drug at 40 °C.     

Encapsulation of Curcumin and Curcumin Derivative in Polymeric Nanospheres

Curcumin and curcumin derivative were loaded on biocompatible methyl methacrylate–hydroxyethyl methacrylate copolymeric nanospheres via in situ microemulsion polymerization. The effect of monomer composition and the emulsifier concentration on the entrapment efficiency, the particle size, and zeta potential of the drug loaded-polymeric nanospheres have been studied. The hydrophilic curcumin derivative was loaded with a high value which reached to about (92 ± 0.5%) against (85 ± 0.8%) recorded for the hydrophobic curcumin. In vitro release of curcumin and its derivative loaded in polymeric nanospheres showed slow and a sustained release pattern.     

Investigation on characterization and transfection of a novel multi‐polyplex gene delivery system

pDNA was condensed by polycationic peptide polylysine (PLL) to form a core, and then encapsulated in biodegradable monomethoxy (poly ethylene glycol)-poly(lactide-co-glycolide)-monomethoxy (poly ethylene glycol) (PELGE) to form core-shell nanoparticles (NPs) as a novel multi-polyplex gene delivery system—PPD(PELGE-PLL-DNA). NPs were prepared by a double emulsification-solvent evaporation technique, using F68 (Pluronic F68, namely Poloxamer 188) as surfactant (not traditional stabilizer PVA), and characterized by morphology, particle size, zeta potential, nuclease, and sonication protection ability, as well as transfection efficiency. Results showed that PPD had a regular spherical shape, with an average diameter of 155 ± 2.97 nm and a zeta potential of −25.6 ± 1.35 mV. PPD could protect plasmid DNA from nuclease degradation and sonication during preparation, while the transfection efficiencies in HepG2 cells and Hela cells were much higher than that of NPs without PLL. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2007     

Self‐assembled amphiphilic poly‐N‐vinylpyrrolidone nanoparticles as carriers for hydrophobic drugs: Stability aspects

Nanoparticles can experience numerous impacts during storage or after intravenous administration resulting in disassembly and/or drug leakage and affecting their efficiency as drug delivery systems. In this study, this crucial issue was addressed by investigating the stability of amphiphilic poly‐N‐vinylpyrrolidone derivative nanocarriers in blood serum, against destabilizing agents and during long‐term storage. All amphiphilic poly‐N‐vinylpyrrolidone derivative nanoparticles prepared in this study were found to possess sizes less than 150 nm, narrow size distribution, spherical morphology, and a slightly negative surface charge. These nanoparticles could efficiently entrap hydrophobic substances (pyrene and curcumin) while retaining excellent compatibility with red blood cells. Moreover, our studies demonstrate the stability of the nanoparticles during long‐term storage and upon dilution with body liquids enhancing their potential as stable in vivo carriers, which is critically important for intravenous drug delivery applications. All properties were found to strongly depend on the ratio between the hydrophobic and the hydrophilic moiety of the polymers under study. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 45637.     

Fabrication, modeling and characterization of multi-crosslinked methacrylate copolymeric nanoparticles for oral drug delivery

Nanotechnology remains the field to explore in the quest to enhance therapeutic efficacies of existing drugs. Fabrication of a methacrylate copolymer-lipid nanoparticulate (MCN) system was explored in this study for oral drug delivery of levodopa. The nanoparticles were fabricated employing multicrosslinking technology and characterized for particle size, zeta potential, morphology, structural modification, drug entrapment efficiency and in vitro drug release. Chemometric Computational (CC) modeling was conducted to deduce the mechanism of nanoparticle synthesis as well as to corroborate the experimental findings. The CC modeling deduced that the nanoparticles synthesis may have followed the mixed triangular formations or the mixed patterns. They were found to be hollow nanocapsules with a size ranging from 152 nm (methacrylate copolymer) to 321 nm (methacrylate copolymer blend) and a zeta potential range of 15.8-43.3 mV. The nanoparticles were directly compressible and it was found that the desired rate of drug release could be achieved by formulating the nanoparticles as a nanosuspension, and then directly compressing them into tablet matrices or incorporating the nanoparticles directly into polymer tablet matrices. However, sustained release of MCNs was achieved only when it was incorporated into a polymer matrix. The experimental results were well corroborated by the CC modeling. The developed technology may be potentially useful for the fabrication of multi-crosslinked polymer blend nanoparticles for oral drug delivery.     

Novel hybrid block copolymer nanocarrier systems to load lipophilic drugs prepared by microphase inversion method

Nanoparticles based on block copolymers of oligosaccharides [β-cyclodextrin (βCyD) and maltoheptaose (Mal₇)] and poly(ε-caprolactone) (PCL) were prepared by microphase inversion method. Zeta-potential, particle size measurements and morphological analysis of drug-free and drug-loaded nanoparticles were performed by using, respectively, laser-doppler anemometry, dynamic and static light scattering and transmission electron microscopy. ρ-Ratio values were correlated with transmission electron microscopy observations. Both types of amphiphilic block copolymers, βCyD-b-PCL_5k and Mal₇-b-PCL_5k, self-assembled in water to form spherical vesicles, presented a hydrodynamic diameter of 72 and 34 nm, respectively. The incorporation of drugs into nanoparticles did not affect significantly the particle size for βCyD-b-PCL_5k-based nanoparticles with progesterone, unlike the other tested systems. On the other hand, all nanoparticles (with and without drug) were negatively charged. Both nanoparticulate systems showed high drug loading efficiency (higher than 95%), confirming their suitability as delivery system for lipophilic drugs.     

PEGylated polylysine derived copolymers with reduction‐responsive side chains for anticancer drug delivery

Reduction‐responsive drug delivery systems have recently gained intense attention in intracellular delivery of anticancer drugs. In this study, we developed a PEGylated polypeptide, poly(ethylene glycol)‐block‐poly(?‐propargyloxycarbonyl‐l ‐lysine) (PEG₁₁₃‐b‐PPAL), as a novel clickable substrate for conjugation of reduction‐responsive side chains for antineoplastic drug delivery. PEG₁₁₃‐b‐PPAL was synthesized through ring‐opening polymerization of alkyne‐containing N‐carboxyanhydride monomers. A designed disulfide‐containing side chain was introduced onto the PEGylated polypeptide by click reaction. The obtained copolymer PEG₁₁₃‐b‐P(Lys‐DSA) formed micelles by self‐assembly, which exhibited reduction‐responsive behavior under the stimulus of 10 mmol L^–1 glutathione (GSH) in water. A small molecule intermediate, compound 2 , was used as a model to investigate the thiol reduction mechanism of PEG₁₁₃‐b‐P(Lys‐DSA) copolymers. The anticancer drug doxorubicin (DOX) was then loaded into the micelles with a drug loading content of 6.73 wt% and a loading efficiency of 40.3%. Both the blank and the drug‐loaded micelles (DOX‐loaded polylysine derived polymeric micelles (LMs/DOX)) adopted a spherical morphology, with average diameters of 48.0 ± 13.1 and 63.8 ± 20.0 nm, respectively. The in vitro drug release results indicated that DOX could be released faster from the micelles by the trigger of GSH in phosphate buffered saline. Confocal laser scanning microscopy and flow cytometer analysis further proved the intracellular delivery of DOX by LMs/DOX and their GSH‐sensitive release behavior. A 3‐(4,5‐dimethyl‐thiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide assay showed that the polymers exhibited negligible cytotoxicity towards normal L929 cells or cancer MCF‐7 cells with a treated concentration up to 1.0 mg mL^–1. In conclusion, our synthesized biocompatible and biodegradable PEGylated polypeptides hold great promise for intracellular antineoplastic drug delivery. © 2019 Society of Chemical Industry     

Mucoadhesive chitosan/OA nanoparticles charged with celecoxib inhibit prostaglandin E2 LPS‐induced in U937 cell line

The present study shows the potential of new carriers of celecocib (CEL) for prostaglandin E2 (PGE2) inhibition in U937 cell line. Self‐assembled nanoparticles based on oleic acid‐modified chitosan were covered with hyaluronic acid (HA) obtaining systems with spherical shape and particle size close to 300 nm. CEL was encapsulated and the encapsulation efficiency (%EE) was dependent of the drug solubility in acid media, reaching %EE of 75.5% and 58.2% to strong and weak acid, respectively. The covering with HA increased the mucoadhesive properties and, the cellular binding and cellular uptake in U937 cells. Nanoparticles prepared in strong acid presented zeta potential (ζ) of 43.8 ± 0.4 mV, which become toxic and stimulate the PGE2 production in U937 cells, at the concentration 1 mg/mL. However, nanoparticles prepared in weaker acid presented ζ of 36.5 ± 1.21 mV, showing nontoxic effect and inhibitory effect of PGE2 from 80.8 pg/mL until 43.4 pg/mL. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134, 45288.     

Novel polysaccharides-based nanoparticle carriers prepared by polyelectrolyte complexation for protein drug delivery

Polyelectrolyte complexation, as one simple and promising method for preparing nanoparticles, is employed to find the use in the delivery of protein drugs. Using this method, we fabricated one kind of novel nanoparticles based on two natural polysaccharides, which are the negatively charged carboxymethyl pachyman (CMP) and the positively charged chitosan (CS). The major effect factors on the average particle size, polydispersity, and zeta potential of the nanoparticles were studied. The research indicated that the physicochemical properties of the nanoparticles were deeply affected by the molecular weight, concentration, and the ionic content of two polysaccharides. The mean particle size of CMP/CS nanoparticles was almost in the range of 100–200 nm for various preparation conditions. The morphology of nanoparticles characterized by a transmission electron microscope was spherical in shape with smooth surface structure. In order to study the feasibility of these nanoparticles as oral protein delivery carriers, the encapsulation efficiency of CMP/CS nanoparticles for bovine serum albumin (BSA) was evaluated for optimized condition. It turned out that the encapsulation efficiency of BSA-loaded CMP/CS nanoparticles varied from 30.1 to 52.9% depending on the initial loading concentration of BSA as well as the concentration of CMP and CS employed in particle formation, which indicated that the concentration of polymers and drugs were all contributed to the encapsulation efficiency of nanoparticles. This report opened up another interesting perspective to develop these natural polysaccharides with emerging new applications, which have great potentials in application in the nanoparticulate delivery system.     

Preparation and characterization of venlafaxine hydrochloride‐loaded chitosan nanoparticles and in vitro release of drug

The venlafaxine hydrochloride (VHL)‐loaded chitosan nanoparticles were prepared by ionic gelation of chitosan (CS) using tripolyphosphate (TPP). The nanoparticles were characterized using FTIR, differential scanning calorimetry, X‐ray diffraction, dynamic light scattering, transmission electron microscopy, and X‐ray photoelectron spectroscopy. The effect of concentration of CS, polyethylene glycol (PEG), VHL and CS/TPP mass ratio on the particle size and zeta potential of nanoparticles was examined. The particle size of CS/TPP nanoparticles and VHL‐loaded CS/TPP nanoparticles was within the range of 200–400 nm with positive surface charge. In the case of VHL‐loaded nanoparticles and PEG‐coated CS/TPP nanoparticles, the particle size increases and surface charge decreases with increasing concentration of VHL and PEG. Both placebo and VHL‐loaded CS/TPP nanoparticles were observed to be spherical in nature. PEG coating on the surface of CS/TPP nanoparticles was confirmed by XPS analysis. Maximum drug entrapment efficiency (70%) was observed at 0.6 mg/mL drug concentration. In vitro drug release study at 37°C ± 0.5°C and pH 7.4 exhibited initial burst release followed by a steady release. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Thermosensitive nanoparticles prepared from poly(N‐isopropylacrylamide‐acrylamide‐vinilpyrrolidone) and its blend with poly(lactide‐co‐glycolide) for efficient drug delivery system

Temperature‐responsive polymers have become increasingly attractive as carrier for the injectable drug delivery systems. In the present work, we have studied the preparation of poly(N‐isopropylacrylamide‐acrylamide‐vinilpyrrolidone) (NIPAAm‐AAm‐VP terpolymer) nanoparticulated terpolymer and its blend with poly(lactide‐co‐glycolide, PLGA; molar ratio of lactide/glycolid 1/3). Thermosensitive terpolymer, poly(NIPAAm‐AAm‐VP) was prepared by free‐radical polymerization in aqueous solution. The nanoparticles of poly(NIPAAm‐AAm‐VP) and its blend with PLGA containing naltrexone were prepared using the evaporation and w/o emulsion‐solvent evaporation methods, respectively. Nanoparticles prepared from terpolymer‐PLGA blend at low polymer concentration (5%) shows larger particle size (>300 nm) and higher drug content%. Various types of nanoparticles showed a burst release of less than 10% after 24 h . The results suggest that by regulating different variables, desired release profiles of naltrexone can be achieved using a blend of PLGA‐poly(NIPAAm‐AAm‐VP) nanoparticulate system. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Optimization of spray-dried diclofenac sodium-loaded microspheres by screening design

The aim of the present study was to investigate the effect of formulation and operating parameters of the laboratory spray dryer on polymeric microspheres intended to be used for sustaining drug delivery of diclofenac sodium (DS). Four operating and four formulation parameters were investigated by Plackett–Burman design to enhance the encapsulation efficiency (EE). The independent variables were air inlet temperature, aspirator, feed flow rate, spray nozzle diameter, amount of drug, amount of polymers, and volume of organic solvent. The resultant microspheres were characterized for their EE. The microspheres having high EE were further characterized for particle size, morphology, and in vitro drug release. Interaction between the drug and the polymer were investigated by Fourier transform infrared (FTIR) spectroscopy and X-ray powder diffractometry (XRPD). The Pareto chart showed that amount of Eudragit® RS100, amount of ethylcellulose, and aspirator were identified as significant factors. The microspheres showed high EE (47.55?±?0.006% to 67.99?±?0.007%). The microspheres were found to be discrete, spherical with smooth surface. The FTIR analysis confirmed the compatibility of DS with the polymers without interaction. The XRPD revealed the dispersion of drug within microspheres formulation. The in vitro drug release from these DS-loaded microspheres showed sustained release of DS over a period of 12?h and followed the Korsmeyer–Peppas model [R²?=?0.9920 (Run 1) and 0.9957 (Run 13)] with a value of the slope (n)?≤?0.43. This n value, however, appears to indicate that Fickian release is the dominant mechanism of drug release with these formulations.     

Formulation and Evaluation of Polymeric Nanoparticulate Gel for Topical Delivery

The aim of the present study was to enhance the permeation of drug into the skin and to reduce the skin irritation. To achieve the objective the drug was formulated in to nanoparticles using chitosan as a polymer and these drug loaded nanoparticles were incorporated in gel. The prepared nanoparticles were characterized by FTIR, DSC, SEM, and particle size. The particle size for optimized nanoparticulate gel (NPG-4) was found to be between 49–305nm. SEM photographs showed that nanoparticles were roughly spherical in shape and free from cracks. The NPG-4 showed 43.9% of encapsulation efficiency and 18.9% drug loading. At the end of 24h the in vitro drug release was found to be 90.1% in pH 7.4 phosphate buffer saline (PBS) and in vitro skin permeation studies NPG-4 showed 2.1mg/cm² of drug permeation, which was better than the marketed formulation (NIZRAL 2%) cream, which showed only 1.2mg/cm² of drug permeation. The NPG-4 showed no primary skin irritation when tested on rabbit skin.     

Antitumor activity of sorafenib-incorporated nanoparticles of dextran/poly(dl-lactide-<Emphasis Type="Italic">co</Emphasis>-glycolide) block copolymer

Sorafenib-incoporated nanoparticles were prepared using a block copolymer that is composed of dextran and poly(DL-lactide-co-glycolide) [DexbLG] for antitumor drug delivery. Sorafenib-incorporated nanoparticles were prepared by a nanoprecipitation-dialysis method. Sorafenib-incorporated DexbLG nanoparticles were uniformly distributed in an aqueous solution regardless of the content of sorafenib. Transmission electron microscopy of the sorafenib-incorporated DexbLG nanoparticles revealed a spherical shape with a diameter < 300 nm. Sorafenib-incorporated DexbLG nanoparticles at a polymer/drug weight ratio of 40:5 showed a relatively uniform size and morphology. Higher initial drug feeding was associated with increased drug content in nanoparticles and in nanoparticle size. A drug release study revealed a decreased drug release rate with increasing drug content. In an in vitro anti-proliferation assay using human cholangiocarcinoma cells, sorafenib-incorporated DexbLG nanoparticles showed a similar antitumor activity as sorafenib. Sorafenib-incorporated DexbLG nanoparticles are promising candidates as vehicles for antitumor drug targeting.     

Ionotropic gelation method in the synthesis of nanoparticles/microparticles for biomedical purposes

The encapsulation of drugs inside polymeric nanoparticles/microparticles is a strategy currently employed in the search for new and more effective therapies. The use of biocompatible and biodegradable polymers gives several advantages to these formulations. Protection of the active principals against the action of environmental and physiological agents, the reduced number of doses and a subsequent decrease in drug‐related adverse effects, and increased bioavailability are some of these advantages. Several methods and materials are now used to synthesize nanoparticles/microparticles for biomedical applications, from carbon‐derived structures to metallic and lipid particles. However, among the methods using polymers, ionotropic gelation is one of the more affordable and easier procedures to perform in daily laboratory work. In this mini‐review, we address relevant characteristics of ionotropic gelation, beginning with basic aspects of the technique, which reagents and conditions are commonly used, the factors affecting the stability of the formulation, the advantages and disadvantages of the method and some principal characterization techniques for the nanoparticulate/microparticulate formulation. Finally, we conclude with a few important considerations. © 2020 Society of Chemical Industry