Preparation of core–shell type nanoparticles of diblock copolymers of poly(L‐lactide)/poly(ethylene glycol) and their characterization in vitro

Core–shell type nanoparticles of poly(L ‐lactide)/poly(ethylene glycol) (LE) diblock copolymer were prepared by a dialysis technique. Their size was confirmed as 40–70 nm using photon correlation spectroscopy. The ¹H‐NMR analysis confirmed the formation of core–shell type nanoparticles and drug loading. The particle size, drug loading, and drug release rate of the LE nanoparticles were slightly changed by the initial solvents that were used. The drug release behavior of LE core–shell type nanoparticles showed an initial burst during the first 12 h and then a sustained release until 100 h. The degradation behavior of LE block copolymer nanoparticles was divided into three phases: the initial rapid degradation phase, the stationary phase, and the rapid degradation phase until complete degradation. It was suggested that lidocaine release kinetics were predominantly governed by the diffusion mechanism in the initial burst phase and after that by both of the diffusion and degradation mechanisms. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 85: 2625–2634, 2002     

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.     

Removal of arsenic from aqueous solutions by an adsorption process with titania–silica binary oxide nanoparticle loaded polyacrylonitrile polymer

A new and simple method was developed to produce gelatin nanoparticles of ～ 30–40 nm for use as carriers for drug release applications. The nanoparticles were uniform in size and well dispersed. An anticancer drug, 5‐fluorouracil, was encapsulated with an efficiency as high as 85%. The nanoparticles showed sustained release of 5‐fluorouracil, and release rates varied with amount of crosslinking in the nanoparticles. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011.     

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     

Production of aceclofenac-loaded sustained release micro/nanoparticles using pressure homogenization and spray drying

The aim of the present study was to characterize polymeric micro/nanoparticles of aceclofenac produced using a high-pressure homogenizer and a spray dryer. The micro/nanoparticles were characterized in terms of their encapsulation efficiency (E.E.), particle size, morphology, and in vitro drug release performance. Interaction between the drug and the polymer (Eudragit RS 100 and ethylcellulose) was evaluated using Fourier transform infrared (FTIR) spectroscopy and X-ray powder diffractometry. Analysis of the results showed that speed and operating pressure have significant negative effect on E.E. of the micro/nanoparticles. The nanoparticles (970–197?nm) had E.E. of 74.09?±?1.17 to 83.66?±?1.63% while microparticles displayed EE. of 72.15?±?2.5%. The micro/nanoparticles were observed to be discrete and spherical. The FTIR analysis confirmed compatibility of aceclofenac with Eudragit RS 100 as well as ethylcellulose. In vitro study showed sustained drug release of 65 and 90% over a period of 12?h, thus prolonging the drug activity to treat the musculoskeletal disorder.     

Preparation and characteristics of pH‐sensitive derivated dextran hydrogel nanoparticles

An optimized procedure was used to prepare erythromycin (EM)‐loaded pH‐sensitive glycidyl methacrylate derivatized dextran (dex‐GMA)/acrylic acid (AAc) nanoparticles. The size distribution and drug release profile at different pH demonstrated that poly(dex‐GMA/AAc) nanoparticles possessed pH‐sensitivity. At pH 1.2, the mean diameter of nanoparticles was about 60 nm. While at pH 7.4 it increased approximately to 250 nm. The release of EM was about 7% of initial loading after 2 h at pH 1.2. However, at pH 7.4 it reached to 17.8%, 30.9% after 2 and 6 h, respectively. The results demonstrated that poly(dex‐GMA/AAc) nanoparticles could release EM slightly while passing through acerbic stomach, whereas in the alkaline intestine the drug is released considerably. The prepared nanoparticles were partially degradable and also had satisfactory biocompatibility. This study suggests that the poly(dex‐GMA/AAc) nanoparticles are potential colon‐specific targeting carriers, which can keep promising pharmaceutical dosage form of EM. POLYM. COMPOS., 2009. © 2008 Society of Plastics Engineers     

In vitro release dynamics of an anticancer drug from swellable gelatin nanoparticles

Gelatin (Type A) nanoparticles were prepared by a single W/O emulsion technique and characterized by infrared (IR) spectra, scanning electron microscopy (SEM), and particle size analysis. The IR spectra clearly confirmed the presence of gelatin and cytarabine in the loaded nanoparticles while the scanning electron micrograph (SEM) image depicts smooth surface, spherical shape and uneven size of nanoparticles (100–300 nm). The prepared nanoparticles were loaded with cytarabine, a well‐known anticancer drug, and the release dynamics of entrapped drug was investigated as a function of various experimental factors, such as percent loading of the drug, chemical architecture of the nanocarriers, and pH, temperature, ionic strength, and nature of the release medium. The nanoparticles were also studied for their water sorption capacity by optical microscopic method taking advantage of the aggregation of nanoparticles. The drug release process was analyzed kinetically using Ficks power law, and a correlation was established between the quantity of released drug and swelling of the nanoparticles. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 101: 2320–2332, 2006     

Carboplatin liposomal nanoparticles: Preparation,characterization, and cytotoxicity effects on lung cancer in vitro environment

The study aimed to encapsulate anticancer drug carboplatin into liposomal nanoparticles by reverse-phase evaporation technique and evaluate its efficacy on lung cancer in vitro environment. Nanoparticles were characterized in terms of size, drug loading efficiency, drug retention capability, and cytotoxicity effects. Nanoscale particles with 67% drug encapsulation efficiency were prepared. Also, high retention capability (drug release equal to 25% after 72?h) of the nanodrug was confirmed. In addition, results of the nanodrug cytotoxicity indicated nanoparticles increased potency of the drug by approximately 90%. Findings of the study indicated liposome can be used for carboplatin delivery to lung cancer.     

Preparation of poly(DL‐lactide‐co‐glycolide) nanoparticles without surfactant

The preparation of poly(DL ‐lactide‐co‐glycolide) (PLGA) nanoparticles was performed by a dialysis method without surfactant or emulsifiers. The size of the PLGA nanoparticles prepared from dimethylacetamide (DMAc) as an initial solvent was smaller than that from acetone. The sizes of the PLGA nanoparticles from DMAc and acetone were 200.4 ± 133.0 and 642.3 ± 131.1 nm, respectively. The effects of the initial solvent selected to dissolve the copolymer and the lactide:glycolide ratio were investigated. The PLGA nanoparticles were spherical as revealed by the results of scanning electron microscopy and transmission electron microscopy observations. From these results it was shown that PLGA nanoparticles could be formed by the dialysis method without surfactant. The drug‐loading contents and efficiency were also dependent on the lactide:glycolide ratio and initial feeding amount of the drug. A higher lactide ratio resulted in higher drug loading and higher loading efficiency. However, a higher initial feeding amount of the drug resulted in higher drug loading and lower loading efficiency. Clonazepam was released for at least 2 days and the release rate was slower with a higher lactide:glycolide ratio and a larger amount of drug‐loading nanoparticles than that with a lower lactide:glycolide ratio and a smaller amount of drug‐loading nanoparticles. © 2001 John Wiley & Sons, Inc. J Appl Polym Sci 80: 2228–2236, 2001     

Production and evaluation of vildagliptin-loaded poly(dl-lactide) and poly(dl-lactide-glycolide) micro-/nanoparticles: Response surface methodology approach

A laboratory scale spray dryer was used to encapsulate vildagliptin (VLG), an antihyperglycemic drug, into different polymers such as poly(dl-lactide) (PDLA), poly(dl-lactide-glycolide)-50:50 (PLGA 50:50), and poly(dl-lactide-glycolide)-75:25 (PLGA 75:25). Response surface methodology (RSM) was employed to evaluate the effects of process and formulation factors on the encapsulation efficiency (EE). The physicochemical properties of the drug-loaded micro-/nanoparticles, mainly the drug loading (DL), particle size distribution, surface morphology, drug–polymer compatibility, and release rate were investigated. % EE of drug-loaded micro-/nanoparticles were in the range of 57.10% to 76.44%. PLGA50:50 micro-/nanoparticles showed highest EE as compared to PDLA and PLGA75:25 micro-/nanoparticles. The mean particle size of the micro-/nanoparticles containing PLGA 50:50, PLGA 75:25, and PDLA polymers were 428?nm, 640?nm, and 1.22 µm, respectively. Surface morphology study revealed smooth, spherical and nonporous surface structures of the micro-/nanoparticles. Fourier transform infrared spectroscopy studies confirmed the drug–polymer compatibility. Powder X-ray diffraction analysis of micro-/nanoparticles revealed that VLG was present in the amorphous form within the micro-/nanoparticles formulations. In vitro release study demonstrated that VLG is slowly released from micro-/nanoparticles for 12?h and the drug release rate was influenced by type and viscosity of polymers used. This work suggests that PDLA, PLGA 50:50, and PLGA75:25 polymers are able to sustain the VLG release rates from micro-/nanoparticles.     

Preparation a core-shell lipid/polymer nanoparticle containing Isotretinoin drug with pH sensitive property: A response surface methodology study

In this study, a core-shell lipid/polymer nanoparticle (NP) was prepared to deliver Isotretinoin drug with pH sensitive and controllable drug release property for oral administration usage. Chitosan was cross-linked to tripolyphosphate to form the core of the NP using the ionic gelation technique and coated with glycerol monostearate lipid as a shell by applying a two-step approach. Response surface methodology was used to investigate the effects of various parameters on particle size and drug entrapment efficiency of the nanoparticles. Optimal nanoparticles with lower particle size and higher entrapment efficiency had a diameter of 100 nm based on TEM analysis and 64% drug entrapment efficiency. Coating NPs surface with lipid changed the NPs charge, hydrophilicity and swelling property. Lipid coating NPs changed release rate from 6 to 4% after 2 h in simulated gastric fluid (SGF), 9 to 16% after 6 h in simulated intestine fluid (SIF) and 21 to 71% after 7 days in blood medium. Kinetic modeling of drug release confirmed Fickian diffusion based on Higuchi model in SIF and blood media where swelling and dissolution of polymer network were negligible, while drug dissolution due to polymer swelling in SGF media was the dominant mechanism for drug release.     

pH‐sensitive polyelectrolyte films derived from submicron chitosan/Eudragit® L 100‐55 complexes: Physicochemical characterization and in vitro drug release

The objectives of this study were to prepare films from submicron chitosan/Eudragit^® L100‐55 polyelectrolyte complexes (CH/EL PEC) and to assess the influence of CH molecular weight and CH/EL mass ratio on their structure and drug‐release properties. The films were obtained by a simple, environmentally friendly, casting/solvent evaporation method and the verapamil hydrochloride (VH) was used as model drug. Submicron size, narrow size distribution, and acceptable stability of CH/EL PECs were confirmed by DLS and laser Doppler microelectrophoresis. SEM analysis revealed nonporous inner structure and flat surface of the films. Interactions between comprising polymers and formation of CH/EL PEC were established by DSC and FT‐IR spectroscopy. In vitro swelling and drug release studies revealed the pH sensitivity of the films, with burst drug release in acidic conditions (pH 1.2) and sustained release in phosphate buffers pH 5.8, 6.8, and 7.4. The slowest VH release was achieved from the films prepared from equal amounts of EL and CH of higher molecular weight, confirming the significance of the CH/EL ratio and CH molecular weight on their ability to sustain drug release. The obtained results suggested that presented, simple, and eco‐friendly preparation procedure can be used to obtain pH‐sensitive CH/EL PEC films with a promising potential as drug carriers. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42583.     

Doxorubicin‐loaded poly(butylcyanoacrylate) nanoparticles produced by emulsifier‐free emulsion polymerization

ABSTRACT: Doxorubicin‐loaded poly(butylcyanoacrylate) (PBCA) nanoparticles (NPs) were prepared by an emulsifier‐free emulsion polymerization technique. The pH values of the polymerization medium and the weight ratios of doxorubicin to butylcyanoacrylate had a significant effect on the mean particle size. The particle diameter determined by transmission electron microscopy showed that the nanoparticles were predominantly less than 50 nm. Drug loading and entrapment efficiency increased with increasing pH of the medium. The surface tension of the polymerization media increased with increasing polymerization time and reached a plateau after 4 h. Doxorubicin‐loaded PBCA NPs carried a positive charge, and the zeta potential of drug‐loaded nanoparticles increased with the increase of the polymerization pH. Molecular weight, analyzed by gel permeation chromatography, showed that the nanoparticles mainly consisted of oligomers of PBCA. The release rate of doxorubicin from nanoparticles in biological phosphate buffer was very slow, with a half‐life of 111.43 h. The results indicate that drug‐loaded nanoparticles can be prepared by an emulsifier‐free emulsion polymerization technique and that the resulting nanoparticles might be suitable for targeting drug delivery vehicles for clinical application. © 2000 John Wiley & Sons, Inc. J Appl Polym Sci 78: 517–526, 2000     

Fabrication of galactosylated chitosan–5‐fluorouracil acetic acid based nanoparticles for controlled drug delivery

In this study, a novel type of macromolecular prodrug, N‐galactosylated chitosan (GC)?5‐fluorouracil acetic acid (FUA) conjugate based nanoparticles, was designed and synthesized as a carrier for hepatocellular carcinoma drug delivery. The GC–FUA nanoparticles were produced by an ionic crosslinking method based on the modified ionic gelation of tripolyphosphate with GC–FUA. The structure of the as‐prepared GC–FUA was characterized by Fourier transform infrared and ¹H‐NMR analyses. The average particle size of the GC–FUA nanoparticles was 160.1 nm, and their drug‐loading content was 21.22 ± 2.7% (n = 3). In comparison with that of the freshly prepared nanoparticles, this value became larger after 7 days because of the aggregation of the GC–FUA nanoparticles. An in vitro drug‐release study showed that the GC–FUA nanoparticles displayed a sustained‐release profile compared to 5‐fluorouracil‐loaded GC nanoparticles. All of the results suggest that the GC–FUA nanoparticles may have great potential for anti‐liver‐cancer applications. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42625.     

Preparation and drug‐release behavior of 5‐fluorouracil‐loaded poly(lactic acid–4‐hydroxyproline–polyethylene glycol) amphipathic copolymer nanoparticles

Poly(lactic acid–4‐hydroxyproline–polyethylene glycol) (PLA–Hpr–PEG) was synthesized via melt copolymerization with stannous chloride as a catalyst activated by a proton acid. Copolymers with different poly(ethylene glycol) (PEG) concentrations (0.1, 0.5, 1, and 5 wt %) were synthesized and exhibited moderate molecular weights (weight‐average molecular weight = 9705–13,600 g/mol) and reasonable molecular weight distributions (weight‐average molecular weight/number‐average molecular weight = 1.35– 1.66). The structure of the polymers was verified with infrared spectroscopy and proton nuclear magnetic resonance spectroscopy. The nanoparticles were made by the nanoprecipitation method with PLA–Hpr–PEG. The size and size distribution of the nanoparticles were investigated with laser light scattering, and the surface morphology of the nanoparticles was investigated with transmission electron microscopy. The drug encapsulation efficiency and drug loading content were measured with ultraviolet absorption spectroscopy. The effects of various formulation parameters were evaluated. The prepared nanoparticles were spherical and greater than 100 nm in size. The drug loading content and encapsulation efficiency were greatly influenced by the amount of the copolymer and the volume of the solvent. The PEG content in the polymer could affect the release of drugs from the PLA–Hpr–PEG nanoparticles. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 2654–2659, 2007     

Development and characterization of ceftriaxone-loaded P3HB-based microparticles for drug delivery

In this study, polymer-based microparticles are used to improve the therapeutic properties of ceftriaxone (CEF) and render them safer. Poly-3-hydroxybutyrate (P3HB) and poly-3-hydroxybutyrate/polyethylene glycol (P3HB-PEG)-based microparticles were prepared by two methods: a double emulsification technique and spray-drying. The microparticles were characterized in terms of size and zeta potential, morphology, total drug loading and drug release. The microparticles had spherical shapes with diameters of a size range from 0.74 to 1.55?µm (emulsification technique) and from 3.84 to 6.51?µm (spray-drying); CEF encapsulation efficiency was around 63% and 49% for these methods respectively. The CEF release from microparticles obtained by spray-drying reached 100% after 150?h, while for microparticles obtained by emulsification technique the total release of CEF did not exceed 34% after 312?h. The release profiles could be best explained by Zero order kinetics model, Higuchi and Korsmeyer-Peppas models, as the plots showed high linearity. Antibacterial activity of the microparticles was evaluated against gram-positive and gram-negative bacterial strains. In general, CEF encapsulation in polymeric microparticles preserves the therapeutic efficacy of the CEF and provides its prolonged effect.     

pH响应改性木质素纳米粒子的制备及释药性能

以酶解木质素（EHL）和N-乙烯基吡咯烷酮（NVP）为主要原料，通过自由基聚合和自组装得到了直径约为50 nm的pH响应性马来酰化木质素-g-聚乙烯吡咯烷酮（MEHL-g-PVP）纳米粒子。考察了化学修饰、聚合物浓度、水滴加速度、搅拌速度、初始水含量和投药量对纳米粒子的形貌、尺寸和载药性能的影响。结果表明，纳米粒子的最大药物负载量可达到35.1%，包封率为64.3%。体外药物释放表明，MEHL-g-PVP具有明显的pH响应能力，在模拟人体内肠道环境和胃液中，布洛芬（IBU）的72h释放量分别为11.1%和63.75%。体外细胞毒性实验结果表明，MEHL-g-PVP载药纳米粒子对正常细胞无细胞毒性，而对结肠癌细胞的具有很好地抑制作用。MEHL-g-PVP纳米粒子有望成为口服药物的理想载体材料。     

Poly(Caprolactone)‐Poly(N‐Isopropyl Acrylamide)‐Fe3O4 Magnetic Nanofibrous Structure with Stimuli Responsive Drug Release

Poly(caprolactone; PCL)—poly(N‐isopropylacrylamie; PNIPAAm)—Fe₃O₄ fiber, that can be magnetically actuated, is reported. Here, a structure is engineered that can be utilized as a smart carrier for the release of chemotherapeutic drug via magneto‐thermal activation, with the aid of magnetic nanoparticles (MNPs). The magnetic measurement of the fibers revealed saturation magnetization values within the range of 1.2–2.2 emu g^?1. The magnetic PCL‐PNIPAAm‐Fe₃O₄ scaffold shows a specific loss power value of 4.19 W g^?1 at 20 wt% MNPs. A temperature increase of 40 °C led to a 600% swelling after only 3 h. Doxorubicin (DOX) as a model drug, demonstrates a controllable drug release profile. 39% ± 0.92 of the total drug loaded is released after 96 h at 37 °C, while 25% drug release in 3 h at 40 °C is detected. Cytotoxicity results show no significant difference in cell attachment efficiency between the MNP‐loaded fibers and control while the DOX‐loaded fibers effectively inhibited cell proliferation at 24 h matching the drug release profile. The noncytotoxic effect, coupled with the magneto‐thermal property and controlled drug release, renders excellent potential for these fibers to be used as a smart drug‐release agent for localized cancer therapy.     

pH sensitive functionalized hyperbranched polyester based nanoparticulate system for the receptor-mediated targeted cancer therapy

The aim of this study is to develop a novel folic acid conjugated, DL-lysine modified, PEGylated, the 3rd generation hyperbranched polymer (HBP-PEG-Lys-FA) for use in receptor-mediated therapy. 5-fluorouracil, model anti-cancer drug, loaded nanoparticles were found an average size of 177?nm with loading efficiency of 23.18%. In vitro drug release studies demonstrated that nanoparticles showed pH-dependent release. HBP-PEG-Lys-FA were efficiently taken up by HeLa cells and specificity of targeted nanoparticles to folate receptors of cells was proved. It was concluded that the HBP-PEG-Lys-FA nanoparticles can provide an advantage on delivering of the drug efficiently into the cytosol for cancer therapy.     

Preparation of nanoparticles composed of chitosan and its derivatives as delivery systems for macromolecules

Three different kinds of nanoparticles for paracellular transport were prepared using a simple and mild ionic‐gelation method. Sodium tripolyphosphate (TPP) as crosslinking agent was added into three kinds of solutions, which were chitosan solution, physical blending solution of chitosan, and glycidyl trimethylammonium chloride (GTMAC), and O‐(2‐hydroxyl) propyl‐3‐trimethyl ammonium chitosan chloride (O‐HTCC) solution respectively. O‐HTCC was synthesized by coupling of GTMAC to chitosan whose functional groups of the NH₂ groups were protected. The nanoparticles were characterized by transmission electron microscopy, atomic force microscopy, photon correlation spectroscopy, and zeta potential measurement. The results showed that increasing TPP concentration promoted the size of chitosan nanoparticles, a decrease in the size of O‐HTCC nanoparticles incurred on the contrary. The size of O‐HTCC nanoparticles is slightly bigger than that of pure chitosan nanoparticles, and smaller than that of physical blending nanoparticles (PBN). Bovine serum albumin (BSA), as a model protein drug, was incorporated into the nanoparticles. Compared with chitosan nanoparticles and PBN, high BSA loading efficiency (87.5%) and loading capacity (99.5%) are achieved by quaternized chitosan (O‐HTCC) nanoparticles, and the release profile of BSA from nanoparticles has an obvious burst effect and a slowly continuous release phase followed. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2007