Drug Carrier For Controlled Release Research Articles

Redox and pH responsive polymeric vesicles constructed from a water-soluble pillar[5]arene and a paraquat-containing block copolymer for rate-tunable controlled release

Herein, for rate-tunable controlled release, pH and redox dual responsive polymeric vesicles were constructed based on host–guest interaction between a water soluble pillar[5]arene (WP5) and a paraquat-containing block copolymer (BCP) in water. The yielding polymeric vesicles can be further applied in the controlled release of a hydrophilic model drug, doxorubicin hydrochloride (DOX). The drug release rate is regulated depending on the type of single stimulus or the combination of two stimuli. Meanwhile, DOX-loaded polymeric vesicles present anticancer activity in vitro comparable to free DOX under the studied conditions, which may be important for applications in the therapy of cancers as a controlled-release drug carrier.

Construction of glucose and H2O2 dual stimuli-responsive polymeric vesicles and their application in controlled drug delivery

Herein, glucose and H2O2 stimuli-responsive vesicles are constructed based on host–guest interaction between a diblock copolymer, poly(ethylene glycol)-b-poly[3-acrylamidophenylboronic acid-co-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl acrylate], (PEG-b-P(PBA-co-PBEM), BCP for short) and α-cyclodextrin. In the presence of glucose, the vesicles are transformed to giant swollen spherical micelles because of the formation of a negatively charged tetravalent form between phenylboronic acid and glucose. On the other hand, the vesicles are totally disassembled when they are exposed to H2O2, which is due to the H2O2-mediated degradation of the pendant phenylboronic acid pinacol ester. The glucose and H2O2 stimuli-responsive vesicles are then applied in the controlled release of water-soluble anticancer drug, doxorubicin hydrochloride (DOX). Upon external stimuli, the DOX displays a faster release rate than that without stimuli. Moreover, the polymeric vesicles show an excellent cytocompatibility toward MCF-7 cells, and the drug-loaded vesicles exhibit a lower cytotoxicity than free drug toward cancer cells. The drug-loaded vesicles can be taken up by MCF-7 cells and further release the DOX in cancer cells due to the high glucose and H2O2 concentration in tumor cells, while they have negligible effect on normal cells, which may be important for applications in the therapy of cancers as a controlled-release drug carrier.

Photo/pH-controlled host–guest interaction between an azobenzene-containing block copolymer and water-soluble pillar[6]arene as a strategy to construct the “compound vesicles” for controlled drug delivery

Herein, dual stimuli-responsive compound vesicles were constructed based on host-guest interaction between a water-soluble pillar[6]arene (WP6) and an amphiphilic azobenzene-containing block copolymers (BCP). Reversible morphological transformation between compound vesicles and solid aggregates was achieved by repeated pH- and photo-stimuli. These compound vesicles were then applied in the controlled release of water-soluble anticancer drug, doxorubicin hydrochloride (DOX · HCl). Upon external stimuli, the DOX · HCl displayed a faster release rate than that without stimuli. Moreover, the compound vesicles showed an excellent cytocompatibility toward the human breast cancer cells (Michigan Cancer Foundation-7, MCF-7), and the drug-loaded compound vesicles exhibited lower cytotoxicity than free drug. The drug-loaded compound vesicles could be taken up by MCF-7 cells and can release the DOX · HCl in cancer cells due to the acid environment, which was important for applications in the therapy of cancers as a controlled-release drug carrier.

Controlled drug release carriers based on PCL/PEO/PCL block copolymers

ABSTRACTIn order to create a new drug delivery system, the ibuprofen-loaded triblock copolymer PCL/PEO/PCL (PCEC) microspheres with a low PEO content (<2 wt%) were prepared by oil in water (o/w) solvent evaporation technique. The influence of PEO content, molecular weight of a polymer matrix and drug loading on the ibuprofen release profiles were evaluated. The interactions between polymer matrix and ibuprofen were detected by FTIR analysis. The presence of hydrophilic PEO segment in PCL chains caused the decrease in particle size, which further had a great impact on the drug release kinetics, i.e., initially faster release and significantly higher quantity of released drug compared to neat PCL. Ibuprofen release behavior from polymer matrix was governed by a diffusion process. In vitro cytotoxicity tests revealed that empty PCL and PCEC microspheres were not toxic at low concentrations, while ibuprofen-loaded microspheres exhibited cytotoxicity correlated with amounts of incorporated drug.

Facile preparation and characterization of pH sensitive Mt/CMC nanocomposite hydrogel beads for propranolol controlled release

The main aim of the present study was to design pH-sensitive nanocomposite hydrogel beads, based on carboxymethyl cellulose (CMC) and montmorillonite (Mt)-propranolol (PPN) nanohybrid, and evaluate whether the prepared nanocomposite beads could potentially be used as oral drug delivery systems. PPN—as a model drug—was intercalated into the interlayer space of Mt clay mineral via the ion exchange procedure. The resultant nanohybrid (Mt-PPN) was applied to fabricate nanocomposite hydrogel beads by association with carboxymethyl cellulose. The characterization of test samples was performed using different techniques: X-Ray Diffraction (XRD), IR spectroscopy (FT-IR), thermal gravity analysis (TGA), and scanning electron microscopy (SEM). The drug encapsulation efficiency was evaluated by UV–vis spectroscopy, and was found to be high for Mt/CMC beads. In vitro drug release test was performed in the simulated gastrointestinal conditions to evaluate the efficiency of Mt-PPN/CMC nanocomposite beads as a controlled-release drug carrier. The drug release profiles indicated that the Mt-PPN/CMC nanocomposite beads had high stability against stomach acid and a sustained- and controlled-release profile for PPN under the simulated intestinal conditions.

The Development and Characterization of Polycaprolactone and Titanium Dioxide Hybrids

Organic/Inorganic hybrid materials have been attracting much attention since they combine the advantages of inorganic materials with the properties of organic polymers. Titanium dioxide nanoparticles (TiO2) present good thermal stability, accessibility and catalytic properties. Polycaprolactone (PCL) is a bi-ocompatible and bioresorbable material, which is being examined as biode-gradable packaging materials, controlled drug release carriers and other medical applications. Hybrids based on PCL containing different amounts of titanium dioxide nanoparticles, ranging from 0.05% to 0.35% w/w, were prepared using the solution cast method. These systems were characterized by X-ray diffraction (XRD), infrared spectroscopy (FTIR), low-field nuclear magnetic resonance (NMR), thermogravimetric analysis (TG) and differential scanning calorimetry (DSC). The FTIR analysis confirmed that there was an interaction between the PCL chains and the TiO2 nanoparticles. The XRD and DSC analysis showed that the PCL crystallization was affected by TiO2 incorporation, modifying its semi-crystalline structure to a less ordered structure. When TiO2 nanoparticles were added the values of T1H and T1ρH increased for all hybrids, therefore, their addition produced a new material with less molecular mobility. In the TG analysis, it was observed that the introduction of TiO2 nanoparticles decreased the thermal resistance of PCL. In DSC analysis, the PCL/TiO2 hybrids presented a reduction in the crystallization temperature and degree of crystallinity, except for PCL hybrids containing 0.15% w/w of TiO2 nanoparticles.

Thermosensitive star polymer pompons with a core-arm structure as thermo-responsive controlled release drug carriers.

In contrast with traditional chemotherapy, controlled drug delivery systems provide many advantages. Herein, a thermosensitive star polymer pompon with a core–arm structure was synthesized using a grafting-on method as a thermo-responsive controlled release drug carrier. Single-chain cyclized/knotted poly tetra(ethylene glycol) diacrylate (polyTEGDA) was used as the hydrophobic core, and thermosensitive linear poly(N-isopropylacrylamide-co-N-methylolacrylamide) (poly(NIPAM-co-NMA)) was selected as the hydrophilic arm. Below or above its lower critical solution temperature (LCST), the linear poly(NIPAM-co-NMA) grafted onto the polyTEGDA core adopted a stretched or curled status, respectively, then the drug could be loaded in or extruded out. The LCST of star polyTEGDA-b-poly(NIPAM-co-NMA) was adjusted to slightly above body temperature (37 °C). The antitumor drug doxorubicin (DOX) was successfully loaded into the pompons with a high loading capacity of 19.45%. The cumulative release of DOX from loaded pompons in vitro for 72 hours was 71% and 20.7% at 42 °C and 37 °C, respectively, indicating that the excellent temperature-controlled release characteristics result from the unique thermo-responsive extrusion effect. Moreover, DOX loaded polyTEGDA-b-poly(NIPAM-co-NMA) pompons achieved better antitumor ability against ovarian carcinoma SKOV3 cells at 42 °C compared with that at 37 °C. These results suggest that star polyTEGDA-b-poly(NIPAM-co-NMA) pompons have considerable promise as thermo-responsive controlled drug delivery carriers.

Anticancer activity of drug-loaded calcium phosphate nanocomposites against human osteosarcoma

BackgroundCalcium phosphate (CaP) based nanoparticles are considered to be ideal drug carriers for delivery of anticancer drugs because of their excellent biocompatibility and pH responsiveness. However, CaP nanoparticles have the problems of limited drug load capacity, initial burst release, and short-term release. Thus, we prepared the CaP nanocomposites containing anticancer drug such as caffeic acid (CA-NP), chlorogenic acid (CG-NP), or cisplatin (CP-NP) in the presence of alginate as a polymer template to control the release rate of drugs.ResultsThe drug-loaded CaP nanocomposites exhibited spherical shape with a size of under 100 nm and the size of nanocomposites was hardly affected by the addition of drug. UV-visible spectroscopic analysis confirmed the insertion of drug into the CaP nanocomposites. These nanocomposites showed an initial burst release of drug, followed by a prolonged release, in which the release profile of drugs was depended on the solution pH. In addition, the drug-loaded CaP nanocomposites revealed anticancer activity on human osteosarcoma in a manner dependent on concentration of drugs and time.ConclusionsThe drug-loaded CaP nanocomposites can contribute to the development of a new generation of controlled drug release carriers for chemotherapy of cancers.

Advance of DNA and CCPs-based nanocarriers in drug delivery systems.

Development of smart and functional polymeric carriers, which enable controlled or timed release of a bioactive material, thereby providing a better dosing pattern and minimizing side effects, becomes a new requirement in the field of drug delivery. In the recent few decades, a great many advancements of polymer synthetic methods have led to a new generation of bioactive polymers' applications as drug controlled release carriers. In this review, we focus on the use of bioactive polymers for drug delivery system, with a particular in the utility of DNA-based nanocarriers and cell-penetrating peptides (CCPs)-based nanocarriers to provide precision control for drug targeting or stimuli responsive systems.

PH and glutathione dual-triggered supramolecular assemblies as synergistic and controlled drug release carriers

Illustration of the formation of β-CD-g-OX-HA/ADA-CPT supramolecular inclusion micelles and their selective release of CPT in tumor cells.

Mediating physicochemical properties and paclitaxel release of pH-responsive H-type multiblock copolymer self-assembly nanomicelles through epoxidation.

pH-Sensitive H-type multiblock copolymers, namely, poly(methacrylic acid)2-block-epoxidized hydroxyl-terminated polybutadiene-block-poly(methacrylic acid)2 (PMAA2-b-epoHTPB-b-PMAA2), were synthesized by atom-transfer radical polymerization and subsequent in situ epoxidation by peracetic acid and characterized by 1H NMR, FT-IR and SEC techniques. The impact of epoxidation on the physicochemical and biomedical properties of copolymer self-assembly micelle nanoparticles was investigated by fluorescence spectrometry, DLS, TEM and an MTT assay. The experimental results indicated that epoxidation resulted in the formation of more stable copolymer micelle nanoparticles with a lower critical micelle concentration, smaller micelle size, and higher loading capacity and encapsulation efficiency of drugs than those without epoxidation. In particular, epoxidized copolymer micelle nanoparticles exhibited reasonable pH sensitivity at a pH of 5.3-5.6. The hydrophobic anticancer drug paclitaxel (PTX) displayed faster release rates from epoxidized nanomicelles than from unepoxidized nanomicelles in a PBS solution of a pH of 4.8-6.6, whereas in PBS of a pH of 7.4 smaller amounts of PTX were released from epoxidized nanomicelles than from unepoxidized nanomicelles. Epoxidized copolymer nanomicelles were reasonably biodegradable after the drug was released, and their degradation rate was faster than that of their unepoxidized counterparts. An MTT assay was performed to determine the biocompatibility of epoxidized copolymer micelle nanoparticles and the anticancer activities of PTX-loaded nanomicelles, which were important for applications in the therapy of cancers as a controlled-release drug carrier.

Controlled-release drug carriers based mesoporous silica spheres with hierarchical hollow/nano structure

Mesoporous silica spheres with hierarchical hollow/nano structure (MSSH-H/N) have been successfully prepared by a template-guided approach, in which cetyltrimethyl ammonium bromide (CTAB) and polystyrene (PS) emulsion was used as the template of mesopores and hollow core, respectively. A consecutive template mechanism and the formation of the hierarchical hollow/nano structure were proposed on basis of the combined characterizations including transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-ray diffraction patterns (XRD) and nitrogen sorption analysis, which showed that the hierarchical structure is composed of mesoporous hollow SiO2 spheres and discrete mesoporous SiO2 nanoparticles coating on the shell. Ibuprofen (IBU) was chosen as a drug model in delivery and release experiments, and these MSSH-H/N samples exhibited higher drug loading capacity, desired low initial IBU release rate and typical two-phase drug release behavior compared with conventional single-structure (single-shelled) hollow mesoporous silica spheres due to their unique hierarchical hollow/nano structure.

Stimulus-responsiveness and methyl violet release behaviors of poly(NIPAAm-co-AA) hydrogels chemically crosslinked with β-cyclodextrin polymer bearing methacrylates

To fabricate thermo- and pH-sensitive hydrogels functionalized with β-cyclodextrin (β-CD) moieties, β-CD polymer bearing methacrylate (CDP-g-GMA) used as a reactive and functional crosslinker was synthesized, and then copolymerized with N-isopropylacrylamide (NIPAAm) and acrylic acid (AA) in aqueous solution via UV-initiated free radical polymerization. The stimulus-responsiveness of the resultant hydrogels has been carried out by measuring the swelling ratio at different temperatures and pH values. The results showed that the thermo- and pH-sensitivities of the produced hydrogels were significantly dependent on the compositions of the hydrogels, and the dual sensitivities exhibited good reversible process. The interior morphology observed by SEM exhibited that the pore size of the hydrogels could be tailored by pH of the local medium. Using a water-soluble cationic dye methyl violet (MV) as a model drug, MV loading and release profiles of the hydrogels as potential drug controlled release carriers were evaluated. The MV release rate from CD-functionalized hydrogels was much slower than that from the hydrogel without β-CDs at both pH 2.0 and pH 7.4. The release of MV from CD-functionalized hydrogels at pH 2.0 was faster than that at pH 7.4, the release kinetics of MV from the CD-functionalized hydrogels displayed a sustained release profile, and the release mechanism followed Fickian diffusion.

Controllable Micro/nano Biofabrication of Fascinating Composites based on Bacterial Cellulose

Event Abstract Back to Event Controllable Micro/nano Biofabrication of Fascinating Composites based on Bacterial Cellulose Guang Yang1 1 Huazhong University of Science & Technology, Department of Biomedical Engineering, College of Life Science & Technology, China Microorganisms in nature have rich variety, whose sizes are from nano to microscale. Therefore, microbes can be used as natural building blocks in nano/micro multilevel fabrication processes. Based on the urgent need of micro/nano biological manufacture of microorganism, four controlling methods: molecular template, magnetic control, microfluidics, and bio-printing for biological manufacture process suitable for microbe have been proposed to dip into the moving mode of microorganism and design new micro/nano functional materials by controlling directed movement and ordered arrangement of microorganism living cells. It could be really creative attempts in the microbial field. Bacterial cellulose (BC) is secreted by microorganism. Its biocompatibility, mechanical strength, chemical and morphologic controllability make it a natural choice for adoption in biomedical fields, including use as biomaterial for wound dressing, artificial blood vessels, vascular grafts, scaffolds for tissue engineering and controlled-release drug carriers. More than that, BC is a natural hydrogel, its high water content can carry other monomeric, reactive and potentially polymerizable species into BC’s inner network, essentially occupying the void volume and interacting with chain segments or pendant moieties of the BC. Therefore, Varity of composites based BC were synthesized and expand the application of BC. BC composites are primarily synthesized through in situ addition of reinforcement materials to BC synthetic media or the ex situ penetration of such materials into BC microfibrils. In our group’s research, Micropatterned BC can be guided neuronal growth, tubular BC can be used as artificial blood vessel. BC combine with biomacromolecules such as chitosan, hyaluronic acid, Au-DAPT nanoparticles, collagen, silk fibroin and so on, can be used in wound dressing and cosmetic. BC combine with Poly(NIPAM-co-BMA), which has thermoresponsive property, suitable for vascular embolization interventional therapy. BC combine with carbon nanotubes or conductive polymers, which has electractive property, can be used as flexible supercapacitor, electrodes, and have potential to be used to build a biology–device interface to produce implantable biosensors, electrostimulated drug release devices, and implantable devices for personalized and regenerative medicine. This work was supported by the National Natural Science Foundation of PR China (21574050, 31270150)

Synthesis and characterization of controlled drug release carriers based on functionalized amphiphilic block copolymers and super‐paramagnetic iron oxide nanoparticles

In this study, synthesis and characterization of magnetic nanocarriers are reported for drug delivery based on the amphiphilic di‐block and tri‐block copolymers of poly(ethylene glycol) (PEG) and poly(ε‐caprolactone) (PCL) with surface modified super‐paramagnetite Fe3O4 nanoparticles (magnetic nanoparticles (MNPs)). The synthesized block copolymers (methoxy poly(ethylene glycol) (mPEG)–PCL and PCL–PEG–PCL) were characterized by Fourier transform infrared (FT‐IR), 1H nuclear magnetic resonance (1H NMR), gel permeation chromatography (GPC), scanning electron microscopy (SEM), and differential scanning calorimetry (DSC), and their properties such as critical micelle concentration, hydrophilicity to lipophilicity balance, and hydrolytic degradation were investigated. The block copolymers were functionalized with terminal azide groups (mPEG–PCL(N3) and (N3)PCL–PEG–PCL(N3)), and magnetic Fe3O4 nanoparticles were surface modified with poly(acrylic acid) (PAA) and propargyl alcohol (MNP–PAA–C≡CH). Magnetic nanocarriers were synthesized by click reaction between azide‐terminated block copolymers and MNP–PAA–C≡CH and characterized by FT‐IR, thermogravimetric analysis (TGA), dynamic light scattering (DLS), vibrating sample magnetometer (VSM), and transmission electron microscopy (TEM), and cytotoxicity was investigated by methyl thiazolyl tetrazolium assay. In vitro drug loading and release and release kinetics were investigated. Copyright © 2015 John Wiley &amp; Sons, Ltd.

Nanoparticulate platforms for targeting bone infections: meeting a major therapeutic challenge.

Bone infections are devastating complications in orthopedics due to biofilm formation. Treatment requires high antibiotic doses, which may lead to systemic toxicity thus limiting the drug therapeutic effectiveness. In this context, nanoparticles are well-known controlled release drug carriers that are able to modulate release rate, versatile in terms of administration routes and may be used as local delivery systems. Regarding bone infections, although nanoparticles are a promising strategy for overcoming biofilm tolerance, there are clearly technical, safety, regulatory and clinical challenges that need to be overcome before such nanomedicines may be translated into clinical use. In this paper, we present a critical overview on the high expectations against the real potential of the nanotechnological approaches to bone infection treatment.

Preparation and characterization of composite hydrogel beads based on sodium alginate

In this report, novel biopolymer hydrogels composed of sodium alginate (SA) and the oxidized sodium alginate (OSA) with an interpenetrating polymer network (IPN) structure were prepared by a combination of chemical and ionic cross-linking approaches. By using SA as the main raw material, OSA was obtained using sodium periodate. The gelation process of the IPN hydrogels was the formation of dual network: one gelatin network cross-linked by OSA with dihydrazide and another SA network cross-linked by Ca2+. The factors which affect its swelling properties were discussed. The best swelling ratio of the beads was 2300, and the swelling property was greatly affected by pH and preparation condition. The stability and swelling behavior of OSA/SA gel beads were better improved than the pure SA/Ca2+ system. The OSA/SA hydrogel beads with the pH sensitivity and stability will be a good candidate for site-specific controlled drug release carrier.

Enhanced the Negative Charges of &lt;i&gt;Antheraea pernyi&lt;/i&gt; Silk Fibroin by Methylglyoxal Modification

Antheraea pernyi silk fibroin has favorable biocompatibility, good bioactivity and controllable biodegradability, meeting the basic requirements of controlled drug release carriers. Enhancing the negative charge of silk fibroin could further increase the encapsulation and loading efficiency of positively charged drugs. In this study, Antheraea pernyi silk fibroin was chemically modified by methylglyoxal in aqueous solution. The electric charge properties of Antheraea pernyi silk fibroin were examined to characterize the modification, the results indicated that the isoelectric point of Antheraea pernyi silk fibroin decreased from 4.5 to 3.9, and the zeta potential reduced from-11.7 mV to-12.8 mV. Amino acid analysis and 1H-NMR spectra showed that arginine residue of Antheraea pernyi silk fibroin side chain was modified by methylglyoxal for enhancing negative charge of silk fibroin. These results suggested that methylglyoxal-modified Antheraea pernyi silk fibroin could be considered as a potential starting material in loading positively charged drugs.

Radiation preparation of drug carriers for dexamethasone and tegafur based on poly(n-isopropylacrylamide) hydrogels

Poly(N-isopropylacrylamide) (PNIPAM) based hydrogels with the lower critical solution temperature (LCST) near the human body-temperature have been obtained from 10% solutions of N-isopropylacrylamide (NIPA) and N,N’-dimethyl acrylamide(DMA) mixture of 90:10 and 85:15 (w/w) by radiation copolymerization and crosslinking using a gamma Co-60 source at a dose of 20 kGy. Water swelling behaviour of the resulting hydrogels was much dependent on the initial ratio of NIPA and DMA. The hydrogels of 85:15 NIPA/DMA was chosen for further investigation for the use as drug cariers.Two kinds of drug carriers were prepared by immerging the hydrogels in solutions containing dexamethasone and tegafur. Then the drug incorporation efficiencies and in-vitro release behaviors of the ingredient were analysed. Loading capacities of the hydrogels were about 48.6 and 95.7 mg per g of dried gel for dexamethasone and tegafur, respectively. The results also revealed that the presence of ions in simulated body fluid and solution temperature much affected to the release behaviors of hydrogels for both dexamethasone and tegafur. Release rates of the ingredients were quite fast for both drug models. These drug-loaded hydrogels were biocompatibility without skin irritation suggesting that they may be used as controlled release drug carriers.

Engineering Biomaterial-Drug Conjugates for Local and Sustained Chemotherapeutic Delivery.

The standard of care for cancer patients includes surgical resection, radiation, and chemotherapy with cytotoxic chemotherapy drugs usually part of the treatment. However, these drugs are commonly associated with cardiotoxicity, ototoxicity, nephrotoxicity, peripheral neuropathy, and myelosuppression. Strategies to deliver cytotoxic chemotherapy drugs while reducing secondary toxicity and increasing tumor dosing would therefore be desirable. This goal can be achieved through the use of controlled release drug carrier systems. The aim of this review is to provide an overview of clinically used drug carrier systems and recently developed approaches for drug-biomaterial conjugation.