Biocompatible Polymer Research Articles

Incorporating surfactants into PCL microneedles for sustained release of a hydrophilic model drug

Polymeric microneedles (MNs) are widely used for sustained drug release due to their distinct advantages over other types of MNs. Poly-ε-caprolactone (PCL) stands out as a biodegradable and biocompatible hydrophobic polymer commonly employed in drug delivery applications. This study explores the impact of surfactants on the encapsulation and release rate of a model hydrophilic drug, minoxidil (MXD), from PCL MNs. Three nonionic surfactants, Tween 80, Span 60, and polyethylene glycol (PEG), were integrated into PCL MNs at varying concentrations. Compared to the other types of surfactants, PEG-containing PCL MNs exhibit enhanced insertion capabilities into a skin-simulant parafilm model and increased mechanical strength, suggesting facile penetration into the stratum corneum. Furthermore, MXD-PEG MNs show the highest encapsulation efficiency and are further characterized using FTIR, DSC and XRD. Their mechanical strength against different static forces was measured. The MNs exhibit a sustained release pattern over 20 days. Eventually, MXD-PEG MNs were subjected to penetration testing using chicken skin and required minimal insertion forces with no observed MN failure during experimentation even after compression with the maximum force applied (32 N per patch). Taken together, the present work demonstrates the feasibility of incorporating nonionic surfactants like PEG into the tips of hydrophobic PCL MNs for sustained delivery of a model hydrophilic drug. This formulation strategy can be used to improve patient compliance by allowing self-administration and achieving prolonged drug release.

Optimized Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) Production by Moderately Haloalkaliphilic Bacterium Halomonas alkalicola Ext

Polyhydroxyalkanoates (PHAs) are biodegradable and biocompatible polymers that are produced by microorganisms as storage materials under limited nutrition and excess carbon. These PHAs have been found to be ideal for replacing synthetic plastics for use in packaging and biomedical applications. In this study, an alkaliphilic and moderately halophilic bacterium Halomonas alkalicola Ext was isolated from Lake Simbi Nyaima in western Kenya and investigated for PHA production. Sudan Black B and Nile Red A staining showed that bacterium had distinct ability for accumulation of PHAs. To optimize PHA production, the bacterium was grown in submerged fermentation under varying culture conditions and different sources and concentrations of carbon and nitrogen. With one-factor-at-a-time (OFTA) approach, optimal PHA yields were obtained after 72 hours at a pH of 10.0, temperature of 35°C, and 2.5% (w/v) NaCl. The bacterium yielded the highest biomass, and PHA amounts on 2% galactose and 0.1% ammonium sulfate as sources of carbon and nitrogen, respectively. A record PHA yield of 0.071 g g-1 with a titer of 1.419±0.09 g/L was achieved from 3.397 g/L of biomass, equivalent to 41.8% PHA content. Using response surface methodology, PHA titer was increased by 1.5% to 1.44 g/L, while PHA content was improved 1.1-fold to 45.57%. Polymer analysis revealed that the extracted PHA was a poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) (3−HB:3−HV=92:8) with two copolymer subunits of 3-hydroxyvaryrate (3-HB) and 3-hydroxybutyrate (3-HV). Halomonas alkalicola Ext attained efficient galactose conversion into PHBV under high salinity and alkalinity conditions.

Electrospun polyvinylidene fluoride with novel facile synthesized functionalized boron nitride quantum dots for neural applications

AbstractThe study aimed to develop a potential biomaterial for neuroregeneration by the electrospinning of the biocompatible polymer polyvinylidene fluoride (PVDF) with innovative functionalized boron nitride quantum dots (F‐BNQDs) synthesized via green chemistry using the amino acid taurine as a functionalization. The F‐BNQDs were characterized and were found to be 16–21 nm in diameter, showed good photoluminescent characteristics, and their elemental composition was confirmed by x‐ray photoelectron spectroscopy, Fourier‐transform infrared (FTIR), and ultraviolet spectroscopy. The PVDF with F‐BNQDs was prepared at three different concentrations, and the resulting electrospun fibers were characterized by scanning electron microscopy, FTIR, thermogravimetric analysis, contact angle, biodegradation, water uptake, Schwann cell cytotoxicity, and cell behavior studies. The results of the study showed that the addition of F‐BNQDs to PVDF resulted in enhanced mechanical properties, decreased contact angle, increased degradability, and water uptake. The lactate dehydrogenase assay revealed that 5% BN‐PVDF had the lowest cytotoxicity. Fluroscent 4',6‐diamidino‐2‐phenylindole (DAPI) staining showed that the increase in F‐BNQD concentration up to 5% BN‐PVDF enhanced cell behavior on the electrospun fibers. Therefore, the study concluded that 5% BN‐PVDF would be suitable for further testing as a potential biomaterial for neuroregeneration in vivo.Highlights Functionalized boron nitride quantum dots (F‐BNQDs) were prepared using amino acid taurine. The F‐BNQDs were characterized and electrospun with polyvinylidene fluoride (PVDF). The incorporation of F‐BNQDs to PVDF has enhanced its physicochemical properties. All samples showed a single βphase PVDF. Schwann cells showed excellent compatibility and cell adhesion on F‐BNQDs/PVDF.

Preparation and Characterization of Acrylic and Methacrylic Phospholipid-Mimetic Polymer Hydrogels and Their Applications in Optical Tissue Clearing.

The 2-methacryloyloxyethyl phosphorylcholine (MPC) polymers are mimetic to phospholipids, being widely used as biocompatible polymers. In our previous study, MPC polymer hydrogels proved more effective for optical tissue clearing compared to acrylamide (AAm) polymer hydrogels. In the present study, 2-acryloyloxyethyl phosphorylcholine (APC) was synthesized and employed to create hydrogels for a comparative analysis with methacrylic MPC-based hydrogels. APC, an acrylic monomer, was copolymerized with AAm in a similar reactivity. In contrast, MPC, as a methacrylic monomer, demonstrated higher copolymerization reactivity than AAm, leading to a spontaneously delayed two-step polymerization behavior. This suggests that the polymer sequences and network structures became heterogeneous when both methacrylic and acrylic monomers, as well as crosslinkers, were present in the copolymerization system. The molecular weight of the APC polymers was considerably smaller than that of the MPC polymers due to the formation of mid-chain radicals and subsequent β-scission during polymerization. The swelling ratios in water and strain sweep profiles of hydrogels prepared using acrylic and methacrylic compounds differed from those of hydrogels prepared using only acrylic compounds. This implies that copolymerization reactivity influences the polymer network structures and crosslinking density in addition to the copolymer composition. APC-based hydrogels are effective for the optical clearing of tumor tissues and are applicable to both passive and electrophoretic methods.

Sequential-Dispersion PGSS process applied to lutein encapsulation at moderate temperatures: A solvent-free method for thermosensitive compound encapsulation

Sequential-Dispersion Particles from Gas Saturated Solutions (SD-PGSS) process was applied to encapsulate lutein with biocompatible polymer excipients to elaborate drug-delivery particles for oral uptake at mild temperatures (38 and 45 °C) under 25 MPa. Polycaprolactone and a polycaprolactone/polyethyleneglycol mixture (1:1 w/w) were selected to modulate in-vitro release. An experimental setup was designed in-house to limit the challenging plugging issues often encountered with the PGSS process. In this study, process yields up to 94% were obtained. The drug precipitation yields varied from 43 to 61% and the homogeneity of lutein dispersion was demonstrated for all conditions. In-vitro release kinetics were performed in phosphate-buffered saline solutions for 8 h. A higher release of lutein was obtained from PCL/PEG blends (∼ 90% in 5 h), whereas only 56% were released from pure PCL formulations. This study highlights the potential of the SD-PGSS process in encapsulating thermosensitive compounds at moderate temperatures.

The Effect of Electrospinning Parameters on the Electrospun Polybutylene Adipate Co-Terephthalate (PBAT) Biodegradable Scaffold

Electrospinning is a cost-effective and versatile technique to fabricate continuous fibers ranging from submicron diameter to nanometer diameter. Polybutylene adipate-co-terephthalate (PBAT) has been investigated as a fibrous scaffold because of its low crystallinity, rapid biodegradability, and excellent mechanical properties, particularly for its high toughness and flexibility. However, the potential of the PBAT fibrous scaffold for medical purposes is still limited. PBAT blends with biocompatible polymers have been developed and investigated for tissue engineering applications. Herein, the preliminary research examines the processability of neat PBAT as a fibrous scaffold by varying several electrospinning processing parameters, such as solution concentration, voltage, flow rate, and tip to collector distance. The aim is to obtain continuous, smooth, and bead-free fibers. The electrospun fibers were examined using a scanning electron microscope (SEM) to determine its diameters. The optimum parameters for obtaining a continuous, bead-free PBAT fibrous scaffold were 20% w/v concentration, 19 kV voltage, 2 mL/h flow rate, and a 15 cm distance.

Influence of the Type of Biocompatible Polymer in the Shell of Magnetite Nanoparticles on Their Interaction with DPPC in Two-Component Langmuir Monolayers.

Magnetite nanoparticles (MNPs) are attractive nanomaterials for applications in magnetic resonance imaging, targeted drug delivery, and anticancer therapy due to their unique properties such as nontoxicity, wide chemical affinity, and intrinsic superparamagnetism. Their functionalization with polymers such as chitosan or poly(vinyl alcohol) (PVA) can not only improve their biocompatibility and biodegradability but it also plays an important role in their interactions with biological cells. In this work, the effect of the functionalization of MNPs with chitosan, PVA, and their blend on model cell membranes formed from 1,2-dipalmitoyl-sn-glycerol-3-phosphocholine (DPPC) using a Langmuir technique was studied. The studies performed showed that the type of biocompatible polymer in the MNP shell plays a crucial role in the effectiveness of its adsorption process into the model cell membrane. Modification of MNPs with chitosan facilitates significantly more effective adsorption than coating them with PVA or with a chitosan and PVA blend. The presence of all the investigated MNPs in the DPPC monolayer at low concentrations does not affect its thermodynamic state, fluidity, or morphology, which is promising in terms of their biocompatibility. On the other hand, their high concentration (molar fraction above ≈0.05) exerts a disruptive effect on the model cell membrane and results in their aggregation, leading probably to the loss of their superparamagnetic properties essential for nanomedicine.

Hollow-adjustable polymer microneedles for prolonged hypoglycemic effect on diabetic rats

Maintaining blood glucose levels within a safe range is critical for diabetic management. In recent decades, microneedles (MNs) have emerged as a potential method for delivering drugs to treat diabetes. However, insufficient drug loading and the complexity of achieving long-acting release have presented challenges that research has not addressed well. In this study, the hollow-adjustable biocompatible polymer MNs with varying cavity volumes were developed by cyclic freeze-thawing technique. The structure of shell-layer of hollow MNs was optimized with a sequential casting approach for regulating drug release kinetics. This design can ensure the sufficient mechanical strength of MNs and help to improve the drug-loading capacity, thereby solving the problem of low drug-loading capacity and short pharmacodynamic action time of traditional polymer MNs. In vivo experiments performed on diabetic rat models revealed the potential of the as-fabricated MNs to effectively pierce into the skin, leading to a notable hypoglycemic effect lasting up to 14 h without inducing the risk of hypoglycemia. These results indicate that the fabricated hollow-adjustable polymer MNs is a potential candidate for transdermal delivery of high-dose drugs.

In vitro study on the inflammatory response of chitosan nanoparticles as a potential siRNA carrier targeting towards osteosarcoma cells

Abstract There have been significant developments in the use of siRNA in the silencing of cancer-allied target proteins with substantial apoptotic effects. Nevertheless, the challenges regarding siRNA delivery for cancer therapy remain a major concern for taking these therapies successfully from laboratory to in vivo studies. Biomaterials are defined traditionally as any material that is used for either medical or dental applications that contact the host cells in any form, such as a drug carrier a device, or as a prosthesis towards the replacement of damaged tissues. The main issues to be fulfilled by the biomaterial for clinical applications are biocompatibility, bioactivity, ability to carry drug to target site, inflammatory responses and other factors based on its application. The present study focuses on the in vitro inflammatory response to the CS nanoparticles using RAW 264.7 and bone marrow derived macrophage cells. Additionally, the in vitro release kinetics of siRNA with varying concentrations and pH, transfection efficacy and biocompatibility were also investigated. The results of siRNA cumulative release increased at pH 5 and 3, which may be corresponding to the protonation, and a delayed release was seen at 7, which was ascribed to unprotonated amine groups inside the CS. The results of release kinetics confirmed a sustained release of siRNA from CS NPs. Considering that CS is a biocompatible polymer, it typically has little impact/damage on cells, as numerous researchers have observed during in vitro experiments. Inflammatory studies were carried out in vitro with RAW 264.7 and BMC cells derived from mice. The gene and protein expression studies showed that the materials might cause some slight inflammation on exposure with both RAW 264.7 and BMC cells in vitro, which is completely negligible. However, putting together the overall data it can be concluded that CS NPs can be a promising material for in vivo applications, which is in agreement with the results of other researchers, but the only concern being its ability to carry siRNA and protect it from nuclease and other enzymatic attacks.

Preparation and performance of biocompatible gadolinium polymer as liver-targeting magnetic resonance imaging contrast agent

A biocompatible macromolecule-conjugated gadolinium chelate complex (PAV2-EDA-DOTA-Gd) as a new liver-specific contrast agent for magnetic resonance imaging (MRI) was synthesized and evaluated. An aspartic acid-valine copolymer was used as a carrier and ethylenediamine as a chemical linker, and the aspartic acid-valine copolymer was covalently linked to the small molecule MRI contrast agent Gd-DOTA (Dotarem) to synthesize a large molecule contrast agent. Invitro MR relaxation showed that the T1-relaxivity of PAV2-EDA-DOTA-Gd (13.7mmol-1Ls-1) was much higher than that of the small-molecule Gd-DOTA (4.9mmol-1Ls-1). Invivo imaging of rats showed that the enhancement effect of PAV2-EDA-DOTA-Gd (55.37 ± 2.80%) on liver imaging was 2.6 times that of Gd-DOTA (21.12 ± 3.86%), and it produced a longer imaging window time (40-70min for PAV2-EDA-DOTA-Gd and 10-30min for Gd-DOTA). Preliminary safety experiments, such as cell experiments and tissue sectioning, showed that PAV2-EDA-DOTA-Gd had low toxicity and satisfactory biocompatibility. The results of this study indicated that PAV2-EDA-DOTA-Gd had high potential as a liver-specific MRI contrast agent.

Magneto-photothermal synergy applied to gold-coated magnetic nanoparticles

In this work, we describe the synthesis of magnetic nanoparticles with a suitable size for easy cellular internalization, avoiding their rapid renal excretion (less than 5 nm) and accumulation in the liver (more than 100 nm). The nanoparticles are functionalized with a biocompatible polymer (low molecular weight, branched polyethylenimine, PEI), and this treatment allows their functionalization with a shell of gold particles in order to improve their ability to absorb electromagnetic radiation in the visible and near infrared wavelength regions. As a result, the magnetic nanostructures are potential agents of local heating (hyperthermia) by exposing them to alternating magnetic fields (magnetic hyperthermia) or to light of the suitable wavelength (photothermia). Magnetic hyperthermia experiments demonstrate that both types of particles can reach the desired temperature range for cell apoptosis, with the difference of a shorter time needed when gold is absent. The released thermal energy is measured by the SAR (specific absorption rate, in W/g), and the values found are promising, up to 600 W/g in the case of uncoated particles. Regarding the photothermia response under the IR radiation, it is comparable for gold-coated and uncoated magnetic particles, but it is enhanced by a factor of almost 10 when the incident light is visible (blue-green) and the particles are provided with their gold shell. Improvements related to the selection of gold particles with resonant absorbance in the infrared are under investigation.

Eco friendly, green route method for the preparation of poly ethylene glycol (PEG) mediated surface modified iron oxide nanoparticles (PEG‐IONps) with potential biological activities

AbstractAmong the various nanoparticles, excessively paramagnetic iron oxide nanoparticles assume an outstanding job in biomedicine, mostly as Nano clinical imaging and treatment. These nanoparticles’ effective working relies on superficial alteration utilizing different specialists. Among them, polyethylene glycol (PEG)—biocompatible polymer is primarily used attributable to its unmistakable qualities. In this examination, the impact of PEG covering on the counter bacterial and against proliferative properties of iron oxide nanoparticles has been considered. PEG‐covered nanoparticles were incorporated by co‐precipitation technique portrayed by UV–visible spectroscopy, Fourier change infrared spectroscopy, electron microscopy, X‐ray diffraction, and vibrating test magnetometer thinks about which uncovers exceptionally stable crystalline, circular, nanoparticles with high polarization impact. Hostile to the bacterial movement was examined against Staphylococcus aureus, and Pseudomonas aeruginosa uncovers PEGlated IONps displayed upgraded action against both tried endure lower fixations. A higher zone of restraint was construed from PEGlated IONps treatment. Hostile to proliferative activity was contemplated against the PC3 cell line (Prostate cancer). PEGlated IONps prompted the most extreme decrease in cell suitability and changed the cell design by chronicle fracture and build‐up of atomic material. PEGlated IONps treatment uncovered a high rate of receptive oxygen species (ROS), which brought about apoptosis or necrotic cell demise. The present discoveries suggest that PEGlated IONps synthesized in this examination could be utilized as potential bioactive operators against medication‐safe pathogenic bacterial strains and malignant growth cells.

A dual catalytic functionalized hollow mesoporous silica-based nanocarrier coated with bacteria-derived exopolysaccharides for targeted delivery of irinotecan to colorectal cancer cells

In this study, we introduced a multifunctional hollow mesoporous silica-based nanocarrier (HMSN) for the targeted delivery of irinotecan (IRT) to colorectal cancer cells. Due to their large reservoirs, hollow mesoporous silica nanoparticles are suitable platforms for loading significant amounts of drugs for sustained drug release. To respond to pH and redox, HMSNs were functionalized with cerium and iron oxides. Additionally, they were coated with bacterial-derived exopolysaccharide (EPS) as a biocompatible polymer. In vitro analyses revealed that cytotoxicity induced in cancer cells through oxidative stress, mediated by mature nanocarriers (EPS.IRT.Ce/Fe.HMSN), was surprisingly greater than that caused by free drugs. Cerium and iron ions, in synergy with the drug, were found to generate reactive oxygen species when targeting the acidic pH within lysosomes and the tumor microenvironment. This, in turn, triggered cascade reactions, leading to cell death. In vivo experiments revealed that the proposed nanocarriers had no noticeable effect on healthy tissues. These findings indicate the selective delivery of the drug to cancerous tissue and the induction of antioxidant effects due to the dual catalytic properties of cerium in normal cells. Accordingly, this hybrid drug delivery system provides a more effective treatment for colorectal cancer with the potential for cost-effective scaling up.

Mimicking Charged Host-Defense Peptides to Tune the Antifungal Activity and Biocompatibility of Amphiphilic Polymers.

Invasive fungal infections impose a substantial global health burden. They cause more than 1.5 million deaths annually and are insufficiently met by the currently approved antifungal drugs. Antifungal peptides are a promising alternative to existing antifungal drugs; however, they can be challenging to synthesize, and are often susceptible to proteases in vivo. Synthetic polymers which mimic the properties of natural antifungal peptides can circumvent these limitations. In this study, we developed a library of 29 amphiphilic polyacrylamides with different charged units, namely, amines, guanidinium, imidazole, and carboxylic acid groups, representative of the natural amino acids lysine, arginine, histidine, and glutamic acid. Ternary polymers incorporating primary ammonium (lysine-like) or imidazole (histidine-like) groups demonstrated superior activity against Candida albicans and biocompatibility with mammalian cells compared to the polymers containing the other charged groups. Furthermore, a combination of primary ammonium, imidazole, and guanidinium (arginine-like) within the same polymer outperformed the antifungal drug amphotericin B in terms of therapeutic index and exhibited fast C. albicans-killing activity. The most promising polymer compositions showed synergistic effects in combination with caspofungin and fluconazole against C. albicans and additionally demonstrated activity against other clinically relevant fungi. Collectively, these results indicate the strong potential of these easily producible polymers to be used as antifungals.

Biomolecules-Loading of 3D-Printed Alginate-Based Scaffolds for Cartilage Tissue Engineering Applications: A Review on Current Status and Future Prospective.

Osteoarthritis (OA) can arise from various factor including trauma, overuse, as well as degeneration resulting from age or disease. The specific treatment options will vary based on the severity of the condition, and the affected joints. Some common treatments for OA include lifestyle modifications, medications, physical therapy, surgery and tissue engineering (TE). For cartilage tissue engineering (CTE), three-dimension (3D) scaffolds are made of biocompatible natural polymers, which allow for the regeneration of new cartilage tissue. An ideal scaffold should possess biological and mechanical properties that closely resemble those of the cartilage tissue, and lead to improved functional of knee. These scaffolds are specifically engineered to serve as replacements for damaged and provide support to the knee joint. 3D-bioprinted scaffolds are made of biocompatible materials natural polymers, which allow for the regeneration of new cartilage. The utilization of 3D bioprinting method has emerged as a novel approach for fabricating scaffolds with optimal properties for CTE applications. This method enables the creation of scaffolds that closely mimic the native cartilage in terms of mechanical characteristics and biological functionality. Alginate, that has the capability to fabricate a cartilage replacement customized for each individual patient. This polymer exhibits hydrophilicity, biocompatibility, and biodegradability, along with shear-thinning properties. These unique properties enable Alginate to be utilized as a bio-ink for 3D bioprinting method. Furthermore, chondrogenesis is the complex process through which cartilage is formed via a series of cellular and molecular signaling. Signaling pathway is as a fundamental mechanism in cartilage formation, enhanced by the incorporation of biomolecules and growth factors that induce the differentiation of stem cells. Accordingly, ongoing review is focusing to promote of 3D bioprinting scaffolds through the utilization of advanced biomolecules-loading of Alginate-based that has the capability to fabricate a cartilage replacement tailored specifically to each patient's unique needs and anatomical requirements.

Recent Advances in 3D Bioprinting of Polysaccharide-based Bioinks for Fabrication of Bioengineered Tissues

Complex multilayered tissues have been regenerated by extrusion-based 3D bioprinting with biocompatible polymers. Multilayer fabrications with tissue-specific bioinks are possible by controlling gel properties including interaction between layers.

Diffusive delivery of plasmid DNA using zwitterionic carboxyalkyl poly(1-vinylimidazole) into skeletal muscle in vivo.

Zwitterionic carboxyalkyl poly(1-vinylimidazole) (CA-PVIm) polymers with imidazolium cations and carboxylate anions have been synthesized as a carrier for the in vivo delivery of plasmid DNA (pDNA) to skeletal muscle. From differential scanning calorimetry measurements, resulting CA-PVIm had intermediate water in hydration water as a biocompatible polymer. Notably, when the pDNA and resulting CA-PVIm were mixed, slight retarded bands of the pDNA were observed in agarose gel electrophoresis, suggesting the polyion complex (PIC) formation between the pDNA and CA-PVIm despite zwitterionic polymers. Resulting PICs maintained the higher-order structure of the pDNA. Using resulting pDNA PICs, the highest pDNA expression by intramuscular injection was achieved in the PIC with 7 mol% carboxymethylated PVIm, that is, CA1(7)-PVIm, observed in a widespread area by in vivo imaging system. These results suggest that the CA1(7)-PVIm/pDNA PIC is effective for the diffusive delivery of the pDNA into skeletal muscle for the treatment of serious muscle diseases.

Synthesis of F127-GA@ZnO nanogel as a cisplatin drug delivery pH-sensitive system.

In this study, a novel drug delivery system based on zinc oxide nanoparticles (ZnO NPs) was developed for the enhanced delivery of cisplatin (CPT) to improve cancer treatment. The ZnO NPs were synthesized from guava leaf extract and then surface-functionalized with gallic acid (GA) to improve their biocompatibility and drug loading capacity. Pluronic F127, a biocompatible polymer, was then conjugated to the GA-modified ZnO NPs to further enhance their stability and cellular uptake. The resulting NPs were characterized by various techniques, including FT-IR, UV-Vis, SEM, TEM, 1H NMR, and DLS. The drug loading and release profiles of CPT from the NPs were investigated, showing high CPT loading capacity and pH-dependent release behavior. The in vitro cytotoxicity of the NPs was evaluated against various cancer cell lines, demonstrating enhanced cytotoxicity compared to free CPT. Overall, this study highlights the potential of GA and Pluronic-modified ZnO NPs as a promising drug delivery system for enhanced CPT delivery and improved cancer therapy.

Microfluidic extensional flow device to study mass transfer dynamics in the polymer microparticle formation process.

Polymer microparticles are often used to encapsulate drugs for sustained drug-release treatments. One of the ways they are manufactured is by using a solvent extraction process, in which the polymer solution is emulsified into an aqueous bulk phase using a surfactant as a stabilizing agent, followed by the removal of the solvent. The radius of a polymer drop decreases as a function of time until the polymer reaches the gelling point, after which it is separated and dried. Among the various operating parameters, the rate of solvent extraction is a critical step that affects the morphology and porosity, and consequently, the kinetics of drug release. But a fundamental mechanistic understanding of the solvent extraction dynamics as a function of shear is still unexplored. In this study, we have developed an experimental mass transfer model to predict the extraction by using the microfluidic extensional flow device (MEFD) to probe the shear and extraction dynamics at the level of a single drop in a linear extensional flow field. We used a computer-controlled feedback algorithm to manipulate the flow field and hydrodynamically trap a Hele-Shaw drop and observe the extraction process. For the polymer solution, we used a biocompatible polymer, poly-lactic-co-glycolic acid (PLGA) with ethyl acetate (EtOAc) as the solvent. Our experiments were conducted by varying the extensional rate (G) in the channel from ∼0.1 s-1 to ∼10 s-1, and using an analytical solution of the flow field, we captured the dissolution process and measured the change in drop radius (R) with time (t). Interestingly, we initially observed a short-time asymptote R ∼ t, and later the long-time asymptote of R = constant; both trends were physically explained. The transport model developed in this work can be used to predict extraction rates and polymer microparticle composition for any polymer-solvent system. This work is also an important contribution to the literature on convective mass transfer in partially miscible emulsions.

First-in-Human Evaluation of a Polymer-Free Everolimus-Eluting Stent Using a Titanium Dioxide Film.

In patients with coronary artery disease treated with permanent polymer-coated drug-eluting stents (DES), the persistent presence of a less biocompatible polymer might delay arterial healing. Thin strut polymer-free DES have the potential to improve clinical outcomes and reduce the duration of dual antiplatelet therapy (DAPT). The purpose of this first-in-human study was to assess the safety and effectiveness of a novel polymer-free DES in patients with de novo coronary lesions. The TIGERevolutioN® stent (CG Bio Co., Ltd., Seoul, Korea) consists of a cobalt chromium platform with a strut thickness of 70 μm and a surface treated with titanium dioxide onto which everolimus-eluting stent (EES) is applied abluminally (6 µg/mm of stent length) without utilization of a polymer. A total of 20 patients were enrolled, with de novo coronary lesions (stable or unstable angina) and > 50% diameter stenosis in a vessel 2.25 to 4.00 mm in diameter and ≤ 40 mm in length for angiographic, optical coherence tomography (OCT), and clinical assessment at 8 months. All patients received DAPT after stent implantation. The primary endpoint was angiographic in-stent late lumen loss (LLL) at 8 months. Twenty patients with 20 lesions were treated with TIGERevolutioN®. At 8 months, in-stent LLL was 0.7 ± 0.4 mm. On OCT, percent area stenosis was 29.2 ± 9.4% and stent strut coverage was complete in all lesions. No adverse cardiovascular event occurred at 8 months. The new polymer-free EES was safe and effective with low LLL and excellent strut coverage at 8 months of follow-up. Trial Registration: Clinical Research Information Service Identifier: KCT0005699.