Porous polyurethane film fabricated via the breath figure approach for sustained drug release

The breath figure (BF) method is an effective process for fabricating porous polymeric films. In this study, we fabricated porous polymer films from thermoplastic polyurethane (PU) through static BF with CHCl₃ as a solvent under 55–80% relative humidity. The porous PU films were prepared within various pore structures and sizes, which were adjustable, depending on the fabrication conditions. The humidity and exposure time were examined as variable parameters affecting the surface morphology, wettability, and cytotoxicity. Atorvastatin calcium, a hyperlipidemic agent, was loaded into the porous films during the casting process, and the drug-loading and drug-releasing behaviors of the porous PU membranes were evaluated. Approximately 60–80% of the drug was released in 14 days. The films exhibited sustained drug-release performances because of the hydrophobicity and nonbiodegradable nature of PU for perivascular drug administration. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 136, 47658.     

Surface modification of multiwalled carbon nanotubes via surface RAFT copolymerization method and capecitabine-loaded anticancer hydrogel for controlled drug delivery in stomach

ABSTRACT

In our work, reversible addition-fragmentation chain transfer (RAFT)/carbon nanotube (CNT)/acrylic acid (AA)/acrylamide (AAm) nanocomposite was synthesized by living radical polymerization. The structure and surface morphology of the synthesized RAFT-CNT-Hydrogel nanocomposites were analyzed by FTIR, ¹HNMR, SEM, TEM, XRD, and TGA/DTG techniques. The results indicated that PAA/AAm chains grafted with CNT by RAFT polymerization. RAFT-CNT-Hydrogel nanocomposites for drug release investigated in different buffers resulted in a strong pH-sensitive behavior. In total, the obtained hydrogel drug-delivery systems are presented a proper effect versus stomach cancer in vitro and in vivo, and it can be used as candidates for controlled release of anticancer drugs in stomach with exalted remedial agents.     

Formulation and evaluation of novel coated floating tablets of bergenin and cetirizine dihydrochloride for gastric delivery

A novel coated gastric floating drug-delivery system (GFDDS) of bergenin (BN) and cetirizine dihydrochloride (CET) was developed. First, the pharmacodynamic studies were performed and the results revealed that the new compounds of bergenin/cetirizine dihydrochloride had comparative efficacy as commercial products (bergenin/chlorphenamine maleate) but with fewer side effects on central nervous system (CNS). Subsequently, bergenin was formulated as an extended-release core tablet while cetirizine dihydrochloride was incorporated into the gastric coating film for immediate release. The formulation of GFDDS was optimized by CET content uniformity test, in vitro buoyancy and drug release. Herein, the effects of sodium bicarbonate (effervescent), hydroxypropyl methylcellulose (HPMC, matrix polymer) and coating weight gain were investigated respectively. The optimized GFDDS exhibited good floating properties (buoyancy lag time < 2?min; floating duration > 10?h) and satisfactory drug-release profiles (immediate release of CET in 10?min and sustained release of BN for 12?h). In vivo gamma scintigraphy proved that the optimized GFDDS could retain in the stomach with a prolonged gastric retention time (GRT) of 5?h, and the coating layer showed no side effect for gastric retention. The novel coated gastric floating drug-delivery system offers a new approach to enhance BN’s absorption at its absorption site and the efficacy of both CET and BN.     

Controlled release of diltiazem hydrochloride

A new type of complex reservoir–matrix system for the controlled delivery of diltiazen hydrochloride was developed. This capsule-type device was designed for oral administration to humans and/or animals. It contained (i) an appropriate amount of the drug in a compartment; (ii) a swelling-controlled membrane which was prepared by mixing polymeric materials with another appropriate amount of the drug; and (iii) a water-soluble gelatin capsule as container. The swelling-controlled membranes were prepared from poly(2-hydroxyethyl methacrylate) hydrogels. The effect of pH on the swelling of the hydrogels was studied. In-vitro dissolution testing was carried out to evaluate the release of the drug using a continuous-flow method. Zero-order release kinetics was obtained over a period of 12 h.     

Preparation and characterization of PEG-modified polyurethane pressure-sensitive adhesives for transdermal drug delivery

Background: The purpose of this work was to develop novel pressure-sensitive adhesives (PSAs) for transdermal drug-delivery systems (TDDS) with proper adhesive properties, hydrophilicity, biocompatibility and high drug loading. Method: Polyethyleneglycol-modified polyurethane PSAs (PEG-PU-PSAs) were synthesized by prepolymerization method with PEG-modified co-polyether and hexamethylene diisocyanate. The effects of reaction temperature, catalyst, ratios of NCO/OH, co-polyether composition, and chain extender were investigated. Drug loading was studied by using thiamazole (hydrophilic drug), diclofenac sodium (slightly hydrophilic drug), and ibuprofen (lipophilic drug) as model drugs. In vitro drug-release kinetics obtained with Franz diffusion cell and dialysis membrane. Results: The results showed that when reaction temperature at 80°C, weight percentage of stannous octoate as catalyst at 0.05%, ratio of NCO/OH at 2.0–2.2, ratio of PEG/polypropylene glycol (PPG)/polytetramethylene ether glycol (PTMG) at 30/25–30/50–55, and weight percentage of glycol as chain extender at 4.5%, PEGPU-PSAs synthesized performed well on adhesive properties. Actually, PEG on the main chain of the PU could improve the hydrophilicity of PSAs, whereas PPG and PTMG could offer proper adhesive properties. Skin compatibility test on volunteers indicated that PEG-PU-PSAs would not cause any skin irritations. All the model drugs had excellent stabilizations in PEG-PU-PSAs. In vitro drug-release kinetics demonstrated that the drug release depended on drug-loading level and solubility of the drug. Conclusion: These experimental results indicated that PEG-PU-PSAs have good potential for applications in TDDS.     

Harnessing the Formation of Natural Killer–Tumor Cell Immunological Synapses for Enhanced Therapeutic Effect in Solid Tumors

The formation of an immunological synapse (IS) on recognition of a cancer cell is the main mechanism underlying the natural killer (NK)-cell-mediated killing of tumor cells. Herein, an integrative strategy for cancer therapy against solid tumors is reported, in which alterations in the cleft of IS, following the secretion of acidic granular content, are utilized as a trigger for the delivery of chemotherapeutic drugs. NK cells are decorated with the IS-environment-responsive micellar system to ensure the release of the payload when they attack cancer cells. Using this strategy, the immunological cytotoxic killing effect of NK cells against solid tumors is reinforced with the site-specific diffusion of chemotherapeutic agents. Harnessing the intrinsic mechanism for the recognition of abnormal cells and the tumor-homing effect of NK cells limit the adverse systemic effects of chemotherapeutic drugs. This approach may provide a pragmatic platform for the universal and effective utilization of IS formation.     

Extracellular Vesicles from Plants: Current Knowledge and Open Questions

The scientific interest in the beneficial properties of natural substances has been recognized for decades, as well as the growing attention in extracellular vesicles (EVs) released by different organisms, in particular from animal cells. However, there is increasing interest in the isolation and biological and functional characterization of these lipoproteic structures in the plant kingdom. Similar to animal vesicles, these plant-derived extracellular vesicles (PDEVs) exhibit a complex content of small RNAs, proteins, lipids, and other metabolites. This sophisticated composition enables PDEVs to be therapeutically attractive. In this review, we report and discuss current knowledge on PDEVs in terms of isolation, characterization of their content, biological properties, and potential use as drug delivery systems. In conclusion, we outline controversial issues on which the scientific community shall focus the attention shortly.     

Hybrid hydrogel based on stereocomplex PDLA/PLLA and gelatin for bone regeneration

Natural bone is a perfect combination of dense shell cortical bone and porous core spongiosa. Inspired by this gradient structure, we prepared a double-layered hydrogel with stereocomplex PDLA-PEG-PDLA and PLLA-PEG-PLLA as the inner porous core and gelatin/nano hydroxyapitite as the outer strengthen shell. Crosslinking of gelatin with natural crosslinker genipin made the shell available for early supporting and the inner physical hydrogel facilitated new bone formation. Successful synthesis of PDLA-PEG-PDLA (or PLLA-PEG-PLLA) was confirmed by ¹H NMR (stands for nuclear magnetic resonance) spectra. The procedure of composite scaffold was monitored with scanning electron microscopy and fourier-transform infrared spectroscopy. In vitro test with mouse preosteoblast MC3T3-E1 cells found that the obtained hybrid hydrogels could improve cell adhesion, proliferation, calcium deposition, and upregulate osteogenesis-related gene expression. Further in vivo experiment on rat calvarial defects also confirmed the capacity of the as-prepared scaffold to accelerate new bone formation. The above data suggested that this core-shell hydrogel helpful for nutrient transportation, bony bridging, and osteoconductivity. But how to control the degradation process of the hydrogel and match with new bone formation still remained challenging.     

Retrograde Axonal Transport of Liposomes from Peripheral Tissue to Spinal Cord and DRGs by Optimized Phospholipid and CTB Modification

Despite recent advancements in therapeutic options for disorders of the central nervous system (CNS), the lack of an efficient drug-delivery system (DDS) hampers their clinical application. We hypothesized that liposomes could be optimized for retrograde transport in axons as a DDS from peripheral tissues to the spinal cord and dorsal root ganglia (DRGs). Three types of liposomes consisting of DSPC, DSPC/POPC, or POPC in combination with cholesterol (Chol) and polyethylene glycol (PEG) lipid were administered to sciatic nerves or the tibialis anterior muscle of mature rats. Liposomes in cell bodies were detected with infrared fluorescence of DiD conjugated to liposomes. Three days later, all nerve-administered liposomes were retrogradely transported to the spinal cord and DRGs, whereas only muscle-administered liposomes consisting of DSPC reached the spinal cord and DRGs. Modification with Cholera toxin B subunit improved the transport efficiency of liposomes to the spinal cord and DRGs from 4.5% to 17.3% and from 3.9% to 14.3% via nerve administration, and from 2.6% to 4.8% and from 2.3% to 4.1% via muscle administration, respectively. Modification with octa-arginine (R8) improved the transport efficiency via nerve administration but abolished the transport capability via muscle administration. These findings provide the initial data for the development of a novel DDS targeting the spinal cord and DRGs via peripheral administration.