pH-responsive drug delivery system based on luminescent CaF(2):Ce(3+)/Tb(3+)-poly(acrylic acid) hybrid microspheres

In this study, we design a controlled release system based on CaF₂:Ce³⁺/Tb³⁺-poly(acrylic acid) (PAA) composite microspheres, which were fabricated by filling the pH-responsive PAA inside CaF₂:Ce³⁺/Tb³⁺ hollow spheres via photopolymerization route. The CaF₂:Ce³⁺/Tb³⁺ hollow spheres prepared by hydrothermal route possess mesoporous structure and show strong green fluorescence from Tb³⁺ under UV excitation. Doxorubicin hydrochloride (DOX), a widely used anti-cancer drug, was used as a model drug to evaluate the loading and controlled release behaviors of the composite microspheres due to the good biocompatibility of the samples using MTT assay. The composite carriers provide a strongly pH-dependent drug release behavior owing to the intrinsic property of PAA and its interactions with DOX. The endocytosis process of drug-loaded microspheres was observed using confocal laser scanning microscopy (CLSM) and the in vitro cytotoxic effect against SKOV3 ovarian cancer cells of the DOX-loaded carriers was investigated. In addition, the extent of drug release could be monitored by the altering of photoluminescence (PL) intensity of CaF₂:Ce³⁺/Tb³⁺. Considering the good biocompatibility, high drug loading content and pH-dependent drug release of the materials, these hybrid luminescent microspheres have potential applications in drug controlled release and disease therapy.     

Artemisinin–Polyvinylpyrrolidone Composites Prepared by Evaporative Precipitation of Nanosuspension for Dissolution Enhancement

Nanoparticles of a poorly water-soluble anti-malarial drug, artemisinin (ART), and its composite particles with a hydrophilic polymer, polyvinylpyrrolidone (PVP), were synthesized using a nanofabrication method called the evaporative precipitation of nanosuspension (EPN). ART nanoparticles and ART/PVP composite particles containing ART nanoparticles coated with PVP were successfully prepared with the aim of improving the dissolution rate of ART. The effect of polymer concentration on the physical and morphological properties, and dissolution rate of the EPN-prepared ART/PVP composite particles was investigated. The crystallinity of ART nanoparticles decreased with increasing polymer concentration, as suggested by the differential scanning calorimetry and X-ray diffraction studies. The phase solubility studies revealed an A_L-type of curve, indicating a linear increase in the drug solubility with PVP concentration. The dissolution of the ART nanoparticles and ART/PVP composite particles markedly increased as compared to that of the original ART powder due to lower particle size and reduced crystallinity of the drug particles. The percent dissolution efficiency (DE), relative dissolution (RD), t _75% and similarity factor (f ₂) were calculated for the statistical analysis. Various mathematical models, viz., zero-order, first-order, Korsemeyer–Peppas and Higuchi, were applied to fit the experimental drug-dissolution data and diffusion was found to be the drug release mechanism.     

Facile synthesis of magnetic-/pH-responsive hydrogel beads based on Fe3O4 nanoparticles and chitosan hydrogel as MTX carriers for controlled drug release

In the present study, methotrexate (MTX)-encapsulated magnetic-/pH-responsive hydrogel beads based on Fe₃O₄ nanoparticles and chitosan were successfully prepared through a one-step gelation process, which is a very facile, economic and environmentally friendly route. The developed hydrogel beads exhibited homogeneous porous structure and super-paramagnetic responsibility. MTX can be successfully encapsulated into magnetic chitosan hydrogel beads, and the drug encapsulation efficiency (%) and encapsulation content (%) were 93.8 and 6.28%, respectively. In addition, the drug release studies in vitro indicated that the MTX-encapsulated magnetic chitosan hydrogel beads had excellent pH-sensitivity, 90.6% MTX was released from the magnetic chitosan hydrogel beads within 48 h at pH 4.0. WST-1 assays in human liver hepatocellular carcinoma cells (HepG2) demonstrated that the MTX-encapsulated magnetic chitosan hydrogel beads had good cytocompatibility and high anti-tumor activity. Therefore, our results revealed that the MTX-encapsulated magnetic chitosan hydrogel beads would be a competitive candidate for controlled drug release in the area of targeted cancer therapy in the near future.     

A new style for synthesis of thermo-responsive Fe3O4/poly (methylmethacrylate-b-N-isopropylacrylamide-b-acrylic acid) magnetic composite nanosphere and theranostic applications

In this work, a novel thermo-responsive Fe₃O₄/poly(methylmethacrylate-b-N-isopropylacrylamide-b-acrylic acid) magnetic composite nanosphere was synthesized for anticancer drug delivery applications. For this propose, the poly(methylmethacrylate-b-N-isopropylacrylamide-b-acrylic acid) [poly (MMA-b-NIPAAm-b-AAc)] was synthesized via reversible addition-fragmentation transfer method. The physic-chemical characterization of the Fe₃O₄/poly(MMA-b-NIPAAm-b-AAc) magnetic composite nanosphere was investigated by FTIR, HNMR spectroscopies and GPC, FESEM, XRD, VSM and DLS. The thermo-sensitivity of the Fe₃O₄/P(MMA-b-NIPAAm-b-AAc) magnetic composite nanosphere was confirmed via DLS at 40 °C. DOX encapsulation efficiency was calculated to be 98.2%. The effect of temperature and pH on release behaviors of stimuli responsive DOX-loaded Fe₃O₄/P(MMA-b-NIPAAm-b-AAc)] magnetic composite nanosphere were investigated. The release rate at pH 7.4, 5.4 and 4 (T = 37 °C) was reached about 24.4, 42.4 and 57.5 wt%, after 4–5 day. The release rate improved at tumor simulated environment (t:40 °C and pH ≤ 5.4). The cytotoxic effects of the magnetic composite nanosphere were appraised by MTT assay and the results indicated that novel developed smart nanocomposite here was nontoxic to MCF-7 cells and can be applied as anti-cancer drug delivery system. Also, the results of the Cellular uptake of MCF7 cells treated with rhodamine labeled DOX-loaded nanocarrier for 2 h have indicated that DOX can be applied as cytotoxic agent and targeting ligand.     

Thermoresponsive magnetic composite nanomaterials for multimodal cancer therapy

The synthesis, characterization and property evaluation of drug-loaded polymer-coated magnetic nanoparticles (MNPs) relevant to multimodal cancer therapy has been studied. The hyperthermia and controlled drug release characteristics of these particles was examined. Magnetite (Fe₃O₄)–poly-n-(isopropylacrylamide) (PNIPAM) composite MNPs were synthesized in a core–shell morphology by dispersion polymerization of n-(isopropylacrylamide) chains in the presence of a magnetite ferrofluid. These core–shell composite particles, with a core diameter of ～13 nm, were loaded with the anti-cancer drug doxorubicin (dox), and the resulting composite nanoparticles (CNPs) exhibit thermoresponsive properties. The magnetic properties of the composite particles are close to those of the uncoated magnetic particles. In an alternating magnetic field (AMF), composite particles loaded with 4.15 wt.% dox exhibit excellent heating properties as well as simultaneous drug release. Drug release testing confirmed that release was much higher above the lower critical solution temperature (LCST) of the CNP, with a release of up to 78.1% of bound dox in 29 h. Controlled drug release testing of the particles reveals that the thermoresponsive property can act as an on/off switch by blocking drug release below the LCST. Our work suggests that these dox-loaded polymer-coated MNPs show excellent in vitro hyperthermia and drug release behavior, with the ability to release drugs in the presence of AMF, and the potential to act as agents for combined targeting, hyperthermia and controlled drug release treatment of cancer.     

Studies on the preparation and controlled release of redox/pH-responsive zwitterionic nanoparticles based on poly-L-glutamic acid and cystamine

The enhancement of tumor intracellular drug uptake and resistance against nonspecific protein adsorption are essential for an injectable anticancer drug carrier. In the present study, a new type of redox/pH-responsive zwitterionic nanoparticles (NPs) was prepared using poly-L-glutamic acid and cystamine in aqueous solutions under mild conditions. The NPs showed surface charge convertible feature in response to pH change of the solutions. The NPs demonstrated excellent anti nonspecific protein adsorption. In vitro release profiles of the NPs, they showed redox/pH dual sensitivities in vitro release. The effective intracellular delivery behaviors were verified through investigation of cell viability, and confocal laser scanning microscopy observation of HeLa cells after incubation with the DOX-loaded NPs. The NPs were non-cytotoxic and would have potential applications as a drug delivery vehicle for enhancing intracellular uptake of anticancer drugs.     

Fabrication and Caffeine Release from Fe3O4/P(MAA-co-NVP) Magnetic Microspheres with Controllable Core–Shell Architecture

A novel route was proposed to design and construct a magnetic composite microsphere consisting of Fe₃O₄ nanoparticles chemically-covalently encapsulated with pH-smart poly(methacrylic acid-co-N-vinyl pyrrolidone) (P(MAA-co-NVP)) cross-linked co-polymers by a surface-initiated radical dispersion polymerization route. The multistep surface treatment was employed to improve the dispersity and surface-chemical reactivity of Fe₃O₄ nanoparticles, involving introduction of active ?NH₂ groups, coupling of 1,1-methylene bis-(4-isocyanato-cyclohexane) and immobilization of 2,2′-azobis[2-methyl-N-(2-hydroxyethyl) propionamide]. The structure and morphological characterization was carried out by FT-IR, TEM, SEM and XRD. The chemically covalent interactions were investigated by FT-IR, TEM, TGA and DSC. The neat Fe₃O₄ nanoparticles took on an aggregated spherical shape with an average diameter of about 12 nm, while Fe₃O₄/P(MAA-co-NVP) magnetic microspheres assumed controllable and monodispersed spheres with a mean dimension of ca. 0.8 μm. The microspheres exhibited superparamagnetic properties. The in vitro caffeine release behavior under varying pH environment was investigated to evaluate the potential of Fe₃O₄/P(MAA-co-NVP) magnetic microspheres as a magnetic drug targeting carrier. The results indicated that the microspheres have a faster drug-release rate at pH 7.4 than at pH 1.4, corresponding to their pH swelling. The kinetic modeling demonstrated that the drug release is controlled by a balance between co-polymer chain relaxation and Fickian diffusion process, and the proposed carrier is suitable for a magnetic targeting drug-delivery system.     

The Effects of Lactidyl/Glycolidyl Ratio and Molecular Weight of Poly(D,L -Lactide-co-Glycolide) on the Tetracycline Entrapment and Release Kinetics of Drug-Loaded Nanofibers

Electrospun tetracycline (Tet)-loaded poly(D,L-lactide-co-glycolide) (PLGA) nanofibers are considered to have great potential as local drug-delivery systems. This study was designed to explore the effects of the lactidyl/glycolidyl (LA/GA) unit ratio and molecular weight of PLGA on Tet entrapment efficiency and in vitro release kinetics. Three kinds of PLGA (PLGA75/25, M _w = 100 000 or 50 000; PLGA50/50, M _w = 50 000) were examined in this study. Electrospun nanofibers were fabricated containing 3, 5, 10 wt% Tet. The results showed that PLGA50/50 entrapped more Tet than both PLGA75/25 co-polymers, and the PLGA75/25 of M _w = 100 000 entrapped the least amount of Tet, suggesting that the lower the molecular weight of PLGA was, the higher the GA content in PLGA was and the higher the resulting Tet entrapment. Tet loading played an important role in Tet release. Nanofibers with 3 and 5 wt% Tet loading exhibited a sustained release for more than 28 days, whereas 10 wt% Tet only lasted 14 days. Loading of 3 wt% Tet resulted in approx. 35% release in the initial 12 h, 5 wt% Tet released approx. 70% and 10 wt% Tet resulted in approx. 85% release. The integrity of Tet incorporated into electrospun PLGA nanofibers was identified by FT-IR spectrum examination and the bacterial inhibition test. The modified Kirby–Bauer test showed dose-dependent inhibition of Staphylococcus aureus growth by Tet, confirming Tet structural stability throughout the electrospinning procedure. MG-63 cells demonstrated good adhesion and proliferation on all PLGA/Tet fibrous membranes. These results indicate that Tet entrapment and release kinetics of PLGA/Tet composite fibrous scaffolds can be tailored by the LA/GA ratios, molecular weights and drug loadings. Tet-loaded fibrous scaffolds show great potential for local drug delivery and bone defect repair.     

pH-responsive nanoparticle assembly from peptide amphiphiles for tumor targeting drug delivery

In this paper, the peptide amphiphiles (PA) which consists of RGDSEEEEEEEEEEK as pH-sensitive segment and stearic acid as hydrophobic segment named RGDS-E₁₀-Lys(C₁₈) was successfully synthesized. TEM images showed that uniformly dispersed nanoparticles could be formed by PA molecules in pH 7.4 medium, however, disintegrated in pH 5.0 medium. Circular dichroism (CD) spectrum indicated that polypeptide adopted a random-coil conformation in neutral medium (pH 7.4). The CD signal was significantly attenuate for decreased solubility of PA in medium with pH 5.0. As expected, the prepared RGDS-E₁₀-Lys(C₁₈) assembly showed high pH-sensitive property which demonstrated a much more rapid drug release from micelles in tumor tissue (acidic environment) than in physiological environment (neutral environment). After DOX-loaded micelles incubated with tumor cells, the cytotoxicity of the micelles against Hela cells was increased obviously, indicating the great potential of micelles developed here as promising vehicle for targeted pH-responsive drug delivery.     

Poly (vinyl alcohol)/SiO2 composite microsphere based on Pickering emulsion and its application in controlled drug release

In this paper, with W/O Pickering emulsion stabilized by modified SiO₂ nanoparticles as template, PVA/SiO₂ composite microspheres with PVA hydrogel cores and shells of SiO₂ nanoparticles are successfully fabricated through freezing/thawing method. The final structure and constituents of the products are investigated through SEM, FTIR, and TGA. The PVA/SiO₂ composite microspheres obtained are applied as a drug carrier to study their controlled release behaviors and methylene blue is used as a model drug. The effect of PVA concentration, SiO₂ nanoparticle concentration, and freezing/thawing cycles on the morphology of products and release behaviors is studied. All release curves are, respectively, fitted by Monoexponential equation, Higuchi equation, Weibull equation, and Hixson-Crowell equation. Weibull equation is found to give the best fit to the release process. The fitted results prove that the drug release from the PVA/SiO₂ composite microspheres follows Fick diffusion.     

The potential of pH-responsive PEG-hyperbranched polyacylhydrazone micelles for cancer therapy

pH-responsive hyperbranched polymers have attracted much attention due to their unique properties for tumor-targeted drug delivery. In this study, we describe a pH-responsive drug carrier, poly (ethylene glycol) (PEG)-hyperbranched polyacylhydrazone (HPAH), which can form nanoscale micelles to be used as anti cancer drug carriers with pH-controlled drug release. The molecular structure of PEG-HPAH was confirmed by nuclear magnetic resonance spectroscopy (NMR) and Fourier transform infrared spectroscopy (FTIR). The drug-loaded micelles with a diameter of approximately 190 nm, were prepared using a dialysis method against PBS with a pH of 8.0. The drug-loaded micelles showed the desired pH-dependent drug release properties. The drug release levels were low at neutral and alkaline pH, but increased significantly with a decrease in the pH of the medium. Intracellular uptake results indicated that the PEG-HPAH-drug micelles could efficiently deliver chemotherapeutic drugs into the cells. In addition, it was found that the subcellular localization of the drug-loaded micelles was different from that of free drugs, in which the drug-loaded micelles were mainly in the cytoplasm. The docetaxel (DTX)-loaded PEG-HPAH micelles presented a high cytotoxic activity against tumor cells in vitro. When combined with the administration of glucose, the PEG-HPAH-DTX micelles exhibited a superior anti-tumor efficacy and a lower systemic toxicity in vivo. The biodistribution profile showed increased accumulated drug levels in tumor tissue and plasma in micelles treated group. The results indicate that the nanoscale PEG-HPAH-DTX micelles may serve as a selective tumor-targeting drug delivery system.     

Preparation and Characterization of pH-Sensitive Anionic Hydrogel Microparticles for Oral Protein-Delivery Applications

pH-sensitive P(MAA-g-EG) anionic hydrogel microparticles having an average diameter of approx. 4 μm were prepared by suspension photopolymerization. The pH-sensitive swelling and release behaviors of the P(MAA-g-EG) hydrogel microparticles were investigated as a biological on–off switch for the design of an oral protein delivery system triggered by external pH changes in the human GI tract. There was a drastic change of the equilibrium weight swelling ratio of P(MAA-g-EG) particles at a pH of around 5, which is the pK _a of PMAA. At pH < 5, the particles were in a relatively collapsed state, while at a pH > 5 the particles swelled to a high degree. When the concentration of the cross-linker of the hydrogel increased, the swelling ratio of the P(MAA-g-EG) hydrogel microparticles decreased at a pH higher than 5 and the pK _a of all the microparticles was in the pH range 4.0–6.0. In release experiments using Rhodamine B (Rh-B) as a model solute, the P(MAA-g-EG) hydrogel microparticles showed a pH-responsive release behavior. At low pH (pH 4.0) only a small amount of Rh-B was released while at high pH (pH 6.0) a relatively large amount of Rh-B was released from the hydrogel particles.     

Rapid dynamic R1/R2*/temperature assessment: a method with potential for monitoring drug delivery

Local drug delivery by hyperthermia‐induced drug release from thermosensitive liposomes (TSLs) may reduce the systemic toxicity of chemotherapy, whilst maintaining or increasing its efficacy. Relaxivity contrast agents can be co‐encapsulated with the drug to allow the visualization of the presence of liposomes, by means of R₂*, as well as the co‐release of the contrast agent and the drug, by means of R_1, on heating. Here, the mathematical method used to extract both R₂* and R₁ from a fast dynamic multi‐echo spoiled gradient echo (ME‐SPGR) is presented and analyzed. Finally, this method is used to monitor such release events. R₂* was obtained from a fit to the ME‐SPGR data. Absolute R₁ was calculated from the signal magnitude changes corrected for the apparent proton density changes and a baseline Look–Locker R₁ map. The method was used to monitor nearly homogeneous water bath heating and local focused ultrasound heating of muscle tissue, and to visualize the release of a gadolinium chelate from TSLs in vitro. R₂*, R₁ and temperature maps were measured with a 5‐s temporal resolution. Both R₂*and R₁ measured were found to change with temperature. The dynamic R₁ measurements after heating agreed with the Look–Locker R₁ values if changes in equilibrium magnetization with temperature were considered. Release of gadolinium from TSLs was detected by an R₁ increase near the phase transition temperature, as well as a shallow R₂* increase. Simultaneous temperature, R₂* and R₁ mapping is feasible in real time and has the potential for use in image‐guided drug delivery studies. Copyright © 2014 John Wiley & Sons, Ltd.     

pH-triggered release of manganese from MnAu nanoparticles that enables cellular neuronal differentiation without cellular toxicity

At high concentrations, manganese (Mn) promotes cellular neurodevelopment but causes toxicity. Here, we report that Mn ion at high concentrations can be delivered to pheochromocytoma 12 (PC12) cells using gold nanoparticles (AuNPs) to enhance cellular neurodevelopment without toxicity. Mn²⁺ release from AuNPs was designed to be pH-responsive so that low pH condition of the cell endosomes can trigger in situ release of Mn²⁺ from AuNPs after cellular uptake of Mn-incorporated AuNPs (MnAuNPs). Due to the differences in reduction potentials of Mn and Au, only Mn ionized and released while Au remained intact when MnAuNPs were uptaken by cells. Compared to PC12 cells treated with a high concentration of free Mn²⁺, PC12 cells treated with an equal concentration of MnAuNPs resulted in significantly enhanced cellular neurodevelopment with decreased apoptosis and necrosis. Treatment with a high concentration of free Mn²⁺ led to an abrupt consumption of a large amount of ATP for the intracellular transport of Mn²⁺ through the ion channel of the cell membrane and to mitochondrial damage caused by the high intracellular concentration of Mn²⁺, both of which resulted in cell necrosis and apoptosis. In contrast, MnAuNP-treated cells consumed much smaller amount of ATP for the intracellular transport of MnAuNPs by endocytosis and showed pH-triggered in situ release of Mn²⁺ from the MnAuNPs in the endosomes of the cells, both of which prevented the cell death caused by ATP depletion and mitochondrial damage. To our knowledge, this is the first report on the use of AuNPs as a vehicle for pH-responsive, intracellular delivery of metal ion, which may open a new window for drug delivery and clinical therapy.     

Controlled release of doxorubicin from graphene oxide based charge-reversal nanocarrier

A number of anticancer drugs, such as doxorubicin (DOX), operate only after being transported into the nucleus of cancer cells. Thus it is essential for the drug carriers to effectively release the anticancer drugs into the cytoplasm of cancer cells and make them move to nucleus freely. Herein, a pH-responsive charge-reversal polyelectrolyte and integrin α_Ⅴβ₃ mono-antibody functionalized graphene oxide (GO) complex is constituted as a nanocarrier for targeted delivery and controlled release of DOX into cancer cells. The DOX loading and releasing in vitro demonstrates that this nanocarrier cannot only load DOX with high efficiency, but also effectively release it under mild acidic pH stimulation. Cellular toxicity assay, confocal laser scanning microscopy and flow cytometer analysis results together confirm that with the targeting nanocarrier, DOX can be selectively transported into the targeted cancer cells. Then they will be effectively released from the nanocarriers in cytoplasm and moved into the nucleus subsequently, stimulating by charge-reverse of the polyelectrolyte in acidic intracellular compartments. The effective delivery and release of the anticancer drugs into nucleus of the targeted cancer cells will lead to a high therapeutic efficiency. Hence, such a targeting nanocarrier prepared from GO and charge-reversal polyelectrolytes is likely to be an available candidate for targeted drug delivery in tumor therapy.     

Analysis of nano drug carriers towards optimum release rate

The aim of this paper is to determine which polymer shape (sphere, hemisphere, cylinder, tablet, cuboid, tetrahedron or octahedron) is best for zero kinetics drug delivery and for sustained nanoparticle release. We applied the Carslaw and Jaeger heat diffusion equations of a sphere with same order of its effective surface area to volume ratio as a reference, to predict how drug delivery would occur in other shapes. The assumption of the heat diffusion analogy in the present study of negligible drug particles is sensible since the drug at nano scale is tiny and thus nearly ‘massless’. From tests involving changing the micro-carrier configuration, we can confirm that shape is an important factor to consider when examining drug release rates, to achieve zero-order design. The preliminary analysis suggests that a hemisphere shape is more promising in achieving zero-order drug release rate, followed by a tablet shape of L = 2R_s, 3R_s, a tetrahedron, a cylindrical shape with L = 3R_s, 2R_s, a sphere, a cuboid shape with L = 3R_s, 2R_s, and finally an octahedron. This is due to the larger effective surface area, given the same parameters and surrounding conditions. In other words, a hemisphere shape reaches zero order in the shortest possible time and thus permits sustained zero-order particle release rate. Based on the ratio between the surface area of a micro-carrier and its volume, we further derived the drug release equation of cylinder/tablet shaped micro-carrier. By introducing h as an index of the similarity of the drug release rate to a desirable zero-order drug release rate, we obtained a relationship between different length/radius (L/R) values of cylinder/tablet shapes and the index h. From this relationship, we find the best L/R ratio that can achieve a drug release process most similar to a zero-order drug release process. Future work is to include optimization of the lipid matrixes.     

New Insights into the Mechanisms of the Interactions Between Doxorubicin and the Ion-Exchange Hydrogel DC Bead™ for Use in Transarterial Chemoembolization (TACE)

Ion-exchange microspheres (IEMs) are widely employed in controlled drug delivery of ionic drugs due to their high loading capacity and the possibility to obtain the controlled release of the loaded drug(s) at a specific site. Among IEMs, DC Bead^? are embolic microdevices (100–300 μm diameter) designed for transarterial chemoembolization (TACE) and composed of cross-linked poly(vinyl alcohol) (PVA) hydrogel, bearing anionic sulfonate moieties on the cross-links, and able to bind cationic drugs such as doxorubicin hydrochloride (Dox). Even if DC Bead^? were studied for their release and bulk characteristics, a thorough characterization of these devices is still lacking. In particular, the aim of this work was the determination of bound and free water, Dox distribution within the microdevices and drug–DC Bead^? interactions, in terms of transport features within the device. Compared with previous results, different Dox radial distributions in DC Bead^? were found, and related to bead microsctructure and ion exchange mechanism. Artifacts due to the self-quenching of Dox at high concentration were prevented and the diffusion coefficients of drug-polymer (Dox-ionic sites) evaluated in different sections of the microspheres. Furthermore, DSC results indicated that in the hydrogel either free (bulk) or bound (non-freezable) water could be found, and that no freezing-bound water was present.     

Preparation and Characterization of TAM-Loaded HPMC/PAN Composite Fibers for Improving Drug-Release Profiles

The present paper reports the preparation and characterization of composite hydroxypropyl methylcellulose/polyacrylonitrile (HPMC/PAN)-medicated fibers via a wet spinning technique. Tamoxifen (TAM) was selected as a model drug. Numerous analyses were conducted to characterize the mechanical, structure and morphology properties of the composite fibers. The drug content and in vitro dissolution behavior were also investigated. SEM images showed that the TAM-loaded HPMC/PAN composite fibers had a finger-like outer skin and a porous structure. FT-IR spectra demonstrated that there was a good compatibility between polymer and drug. Results from X-ray diffraction and DSC suggested that most of the incorporated TAM was evenly distributed in the fiber matrix in an amorphous state, except for a minority that aggregated on the surface of fibers. The drug content in the fibers was lower than that in the spinning solution and about 10% of TAM was lost during spinning process. In vitro dissolution results indicated that, compared to TAM–PAN fibers, HPMC/PAN composite systems had weaker initial burst release effects and more drug-loading. The combination of hydrophilic polymer HPMC with PAN could improve the performance of polymer matrix composite fibers in regulating the drug-release profiles.     

Preparation of alginate hydrogels through solution extrusion and the release behavior of different drugs

Homogeneous alginate hydrogels were facilely fabricated through solution extrusion process. CaCO₃ and D-glucono-δ-lactone (GDL) were used as the gelation agents. The slow gelation of alginate was realized by the in-situ release of Ca²⁺ from CaCO₃ particles induced by hydrolysis of GDL to reduce pH. Slight gelation during the extrusion caused the enhanced strength of the alginate solutions, leading to the extrudability of the blends. This method enables to produce alginate hydrogels in a single step via extrusion, which is economically advantageous to conventional lab-scale preparation for mass production. Three different drugs, ibuprofen, acetaminophen, and methylthionine chloride, were used as model drugs to evaluate the drug release behavior of the alginate hydrogels. It was demonstrated that the drug release behavior was significantly adjusted by both the drug solubility and the ionic interaction between alginate and the drug molecule. It was shown that solution extrusion process is a feasible method to produce alginate-based drug delivery systems.     

Planar microdevices enhance transport of large molecular weight molecules across retinal pigment epithelial cells

Large molecular weight drug delivery to the posterior eye is challenging due to cellular barriers that hinder drug transport. Understanding how to enhance transport across the retinal barrier is important for the design of new drug delivery systems. A novel mechanism to enhance drug transport is the use of geometric properties, which has not been extensively explored in the retina. Planar SU-8/Poly(ethyleneglycol)dimethacrylate microdevices were constructed using photolithography to deliver FITC dextran across an in vitro retinal model. The model consists of retinal pigment epithelial (RPE) cells grown to confluence on transwell inserts, which provides an environment to investigate the influence of geometry on paracellular and transcellular delivery of encapsulated large molecules. Planar microdevices enhanced transport of large molecular weight dextrans across different models of RPE in a size dependent fashion. Increased drug permeation across the RPE was observed with the addition of microdevices as compared to a traditional bolus of FITC dextran. This phenomena was initiated by a non-toxic interaction between the microdevices and the retinal tight junction proteins. Suggesting that increased drug transport occurs via a paracellular pathway. These experiments provide evidence to support the future use of planar unidirectional microdevices for delivery of biologics in ocular applications.