Polymer Core Research Articles

Low-cost prototyping of nitinol wires/frames using polymeric cores and sacrificial fixtures with application in individualized frames anchoring through the atrial septum

Self-expanding frames for minimally invasive implants are typically made from nitinol wires and are heat treated to maintain the desired shapes. In the process of heat treatment, nitinol structures are placed in a high-temperature oven, while they are confined by a fixture. During this process, nitinol exerts a high amount of force. Accordingly, a fixture requires high mechanical strength and temperature resistance; this is why fixtures are typically made from metals. The use of metal fixture also increases the turnaround time and cost. However, accelerating this process is beneficial in many applications, such as rapid development of medical implants that are patient-specific. Inspired by the use of sacrificial layers in microfabrication technology, here we propose a novel method for shape setting nitinol wires using a sacrificial metal fixture. In this process, the nitinol wires are first aligned inside copper hypotubes. Next, the forming process is done using hand-held tools to shape complex geometrical structures, annealing the nitinol reinforced by copper, and then selectively etching copper hypotubes in ammonium persulfate solutions. In this process, other sacrificial cores, which are 3D printed or cast from low-cost polymers, are also used. This combination of polymeric cores and minimal use of metals enables reducing the cost and the turnaround time. As a proof of concept, we showed that this process was capable of fabricating springs with mm or sub-mm diameters. The result showed a change of less than 5% in the intended diameter of the nitinol spring with diameters ranging from ~ 0.7 to 1.9 mm, which confirms copper as a suitable sacrificial fixture to obtain the desired complex geometry for nitinol. A metric, based on the elastic strain stored in copper is suggested to predict the possible variation of the intended dimensions in this process. Finally, to demonstrate the potential of this method, as proof of concept, we fabricated NiTi wire frames designed for anchoring through the atrial septum. These frames demonstrated septal defect occluders that were designed based on a patient’s cardiac image available in the public domain. This low-cost rapid fabrication technique is highly beneficial for a variety of applications in engineering and medicine with specific applications in rapid prototyping of medical implants.

Polyacrylonitrile and polyethersulfone based co-axial electrospun nanofibers for fluoride removal from contaminated stream

Coaxial electrospun polyacrylonitrile (PAN) and polyethersulfone (PES) based nanofibers were prepared and was used for filtration of fluoride from drinking water for the first time. Well defined fiber geometry was obtained at 1 ml/h of core polymer, i.e., PES flow rate, 1.4 ml/h of shell polymer, i.e., PAN flow rate, voltage of 22 kV, while the distance between the needle tip and the collector was 15–17 cm. Increase in bead like structure in fiber strands was observed with higher PAN concentration, while it decreased for lower PES concentration, thereby giving an optimum composition (6 wt% PAN and 10 wt% PES) for uniform fiber morphology. This nanofiber, abbreviated as N2 acted as an ultrafiltration membrane having permeability in the lower range, i.e., 0.5 × 10−11 m/s Pa and its fluoride removal efficacy was 46%. Fibers were also hydrophilic with considerable porous nature. Uptake of fluoride by this N2 nanofibers were evident from binding energy of 685.2 eV during XPS analysis. It is probable that nitrile and sulfone groups present in the core and shell of the nanofibers played an active in fluoride uptake, which was estimated as 110 mg/g at 298 K. Isoelectric point was in alkaline range which promoted negative fluoride ion uptake on positive nanofiber surface. Lead played higher masking effect in the uptake of fluoride in comparison to arsenic as coexisting ion. Dynamic cross flow filtration was also studied with this nanofiber in both synthetic and real life feed solution.

Formulation and evaluation of dabigatran loaded microballoons for prolonged drug release

The objective of the present investigation was to formulate microballoons loaded with dabigatran in the polymeric core for achieving sustained release and hence improved bioavailability. Microballoons loaded with dabigatran in the polymer shell were prepared by simple solvent evaporation method using either ethyl cellulose alone or a blend of ethyl cellulose with HPMC/PVP-K30/Eudragit S100/Methyl cellulose in a fixed ratio. The percent yield of the microballoons ranged from 38.7 to 62.4% with highest yield obtained in F3. The particle size was measured using optical microscopy and the particles were observed to be spherical in shape. The particle size ranged from 28.50 ± 16.378 µm (F3) to 48.14 ± 16.748 µm (F1). The angle of repose ranged from 26.37° to 28.09° and the Carr’s index and Hausner’s ratio were in between 6.38 to 19.95 and 1.07 to 1.25 respectively. It was found that all the formulations exhibited buoyancy in the range of 61.42 to 71.71% over a period of 8h. This suggests that the formulations were able to float for sufficient time and would be able to control the release of dabigatran for longer duration. The in vitro drug release study depicted that the highest amount of drug was released from F3 (66.79%) while the lowest was released from F1 (50.27%) at the end of 8 hours of study.

Flexural behavior evaluation of a foam core curved sandwich beam

In this study, curved sandwich beams (CSBs) with glass fiber-reinforced polymer (GFRP) and polyethylene terephthalate (PET) foam core were initially fabricated. Experiments in three-point bending were then performed to understand the flexural behaviors including failure modes, load-bearing capacities, and load–displacement curves. The effects of various geometrical parameters including facesheets and core thicknesses, two different types of cores, and curvature radius were clarified. It was found that the utilization of PET foam in CSBs resulted in a prevention of core shearing failure and a gradual decrease in load–displacement response. Moreover, the results showed that the ultimate load-bearing capacity and stiffness of the CSBs decreased by 17.7 % and 61.8 %, with a curvature decreased from 1500 to 300 mm, respectively. An analytical model was performed to accurately estimate the experimental failure modes and load-bearing capacities of CSBs. Failure maps were also developed to investigate the various failure modes caused by different geometric parameters of curved sandwich beams. The failure maps offer valuable guidance for the design of lightweight structures.

Development and In Vitro Evaluation of Nanoparticles of Silymarin Using Central Composite Design

Silymarin is a phytoconstituent derived from the plant Silybum marianum with poor oral absorption and bioavailability but possesses hepatoprotective activity, anticancer activity, cardioprotective, neuroprotective, stabilizing, anti-inflammatory, and antioxidant activity. Therefore, the current work aims to develop a nanoformulation of silymarin to increase bioavailability, reduce dosing frequency, minimize toxicity, and improve patient compliance. Silymarin nanoparticles were created via the ionic gelation technique, employing chitosan and TPP as the primary polymers. A central composite design was employed for formulation optimization. Chitosan and TPP were employed as independent variables, while particle size and encapsulation efficiency were considered as dependent variables. The prepared nanoparticles were evaluated through entrapment efficiency, in vitro drug release, and drug-excipient interaction studies. Thirteen experiments were conducted using the experimental runs created by the central composite design. The average particle size was between 149nm and 294nm. The encapsulation efficiency percentage was between 65.4% and 87.3%. The polydispersity index had a value of 0.437. The zeta potential of the optimized formulation was determined to be 38.1 mV. The compatibility studies between the drug and excipients were confirmed using Fourier Transform Infrared Spectroscopy and Differential Scanning Calorimetry. The successful encapsulation of silymarin within the polymer core was verified through scanning electron microscopy analysis. The silymarin-loaded nanoparticles were observed to have a significant drug release of 98,942.43% over 24 hours. The outcomes of the study of Silymarin nanoparticles showed a substantial increase in the dissolution rate, which can be ascribed to the changed solubility properties of the drug. This result is consistent with the stated aim of improving drug absorption. Keywords: Silymarin, nanoformulation, central composite design.

The effect of fuzzy fiber-reinforced composite skin on bending stiffness and debonding growth between skin and polymeric foam core of sandwich structures

Progressive innovations in the field of nanotechnology demonstrate that through the radial growth of aligned carbon nanotubes (CNTs) on the circumferential surfaces of fibers known as fuzzy fibers, the transverse elastic properties of fiber-reinforced composites are notably improved. The main objective of the present work is to numerically examine the effects of using fuzzy fiber-reinforced composite (FFRC) skins on the flexural behavior of sandwich structures. Based on the considered two-stage analysis, in the first instance, the mechanical properties of FFRC are determined by the simplified unit cell (SUC) micromechanical model. Afterward, by simulating the three-point bending test via the finite element method (FEM), major assessments are accomplished to reflect the effects of microstructure-level features, including fiber and CNT volume fractions, CNT/polymer interphase, and CNT diameter, on the bending stiffness and debonding growth between the FFRC skin and polyvinyl chloride (PVC) foam core. The results reveal the satisfactory influence of employing FFRC skins on improving the flexural behavior of sandwich structures.

DEVELOPMENT, CHARACTERIZATION AND EVALUATION OF ENTRECTINIB NANOSPONGES LOADED TABLETS FOR ORAL DELIVERY

Objective: As Entrectinib is a lipophilic, basic, moderately permeable molecule with strongly pH-dependent solubility with antitumor activity in advanced and metastatic solid tumors, the current study was designed to improve the oral solubility of Entrectinib through incorporation into nanosponges tablets (NSs). Methods: Box-Behnken Design was used to optimize the independent variables of β-Cyclodextrin (β-CD) NSs formation. β-CD NSs were prepared by an ultrasound-assisted method using diphenyl carbonate as cross-linking agent, which were later characterized and formulated into tablets by wet granulation method. The prepared tablets were evaluated for the physico-chemical properties and in vitro release of the drug. Results: A series of fifteen experiments were performed based on the experimental runs generated from a three-factor, three-level Box–Behnken design (BBD). The range of mean particle size was 149-294 nm, the range for encapsulation efficiency % was 65.4%-87.3%, and the value for polydispersity index was 0.437. The zeta potential for the optimized formulation was found to be 38.1 Mv. The drug and excipients were compatibles as confirmed by Fourier Transformed Infrared (FTIR) Spectroscopy and Differential Scanning Calorimetry (DSC) studies. Scanning Electron Microscopic (SEM) analysis confirmed that the Entrectinib has successfully entrapped in the core of polymer. In vitro release of the Entrectinib-loaded NSs tablets (six compositions) were compared with a marked product and satisfactory results were obtained. It was observed that rapid dissolution occurred in 0.1 N HCl for first 2 h (15.64±1.52% vs. 12.67±1.89%) and 98.94±2.43% of drug release was observed in Entrectinib loaded NSs and 91.78±1.37% in marketed product in 24 h. The prepared formulations were stable during 6 mo stability study period. Conclusion: The study results studies of Entrectinib NS tablets indicated rapid dissolution due to changed solubility properties of the drug, compared to pure drug meeting the set objective of enhanced absorption. The formulated Entrectinib-loaded NSs can be beneficial in the treatment of cancers.

ISX9 loaded thermoresponsive nanoparticles for hair follicle regrowth

There is a high demand for an optimal drug delivery system to treat androgenetic alopecia. Topical application of ISX9, which is a neurogenesis inducer, has been found to stimulate hair follicle (HF) regrowth by upregulating the Wnt/β-catenin signaling pathway, an essential pathway involved in initiating HF growth and development. In the present study, a temperature-sensitive, biopolymer-based, biocompatible, and eco-friendly drug-delivery system was synthesized. This system comprised chitosan-grafted poly(glycidyl methacrylate-co-N-isopropyl acrylamide) (Poly(GMA-co-NIPAAm)@CS-PGNCS) as the shell component and PF127 as the core polymer. The hydrophobic nature of the PF127 block copolymer efficiently dissolved the partially water-soluble drug, ISX9, and the thermos-responsive shell polymer effectively released the drug at a definite skin temperature. The optimized spherical nanoparticles demonstrated the lowest critical solution temperature (LCST) at 32 ± 2 °C with a diameter of 100–250 nm, which delivered encapsulated ISX9 with greater precision than topical ISX9. In a series of in vivo experiments, we demonstrated that ISX9-coated TBNPs upregulated the expression of β-catenin, active β-catenin, Wnt target genes, stemness marker genes, proliferating cell nuclear antigen, HF stem cell markers, and HF markers including VEGF, TGF, and IGF-1 more effectively than topical ISX9. These results suggest that TBNPs could be employed as a platform for effective transdermal delivery of various hydrophobic drugs.

Thermosensitive Micelles Gel to Deliver Quercetin Locally for Enhanced Antibreast Cancer Efficacy: An In Vitro Evaluation.

Although quercetin is low cytotoxicity to normal human cells, quercetin is effective against the growth of some tumors. Given the poor blood stability in vivo, insolubility, low delivery efficiency, and poor medicinal properties of quercetin, we developed a local drug delivery system comprising quercetin core's polymer micelles and F127 hydrogel stroma. In vitro evaluation revealed that quercetin core's polymer micelles have excellent antitumor activity and could inhibit the multiplication of 4T1 breast cancer cells through the apoptosis pathway. Meanwhile, a rheological study revealed that the quercetin core's micelles gel possessed excellent properties of hydrogel formation and injectability of liquid preparation as a local drug delivery system after the quercetin core's polymer micelles were loaded into the F127 hydrogel stroma. Our study findings indicated that the drug stability and stable release capacity of quercetin were vastly improved with the composite formulation of the micelles gel. This not only realized drug injectability but also drug storage in the semisolid form, which is a more comfortable and slower drug-releasing form that will eventually exert a proper therapeutic effect. In conclusion, quercetin micellar hydrogel system has better antitumor activity and excellent hydrogel properties.

Multi-objective optimization of sandwich structures for reinforcing composite fuselages

This study introduces a simulation-based optimization approach that combines a multi-objective genetic algorithm and the finite element method to design sandwich structures to reinforce composite fuselages. The sandwich structure has been parametrized with a set of mixed integer-continuous variables representing the polymer core thickness, the number and weight of laminated fiberglass layers, and size and position of the structure. Automatic scripting builds the geometry of the structure, then mounts it in the fuselage, and finally creates a conformal mesh. During the optimization, each reinforced fuselage is subjected to several load cases specified by the CS-22 EASA design standard, determining the worst load condition. Two objectives were considered: increasing the reinforced fuselage’s minimum fiber stress safety factor for improved safety and reducing the number of layers of the sandwich structure to minimize manufacturing costs. Structural constraints were the mass of the sandwich structure and buckling and flexo-torsional deformation of the reinforced fuselage. Results show an efficient material arrangement due to the reduced number of layers in the sandwich structure and a stress safety factor surpassing that set by the standard. Finally, the reinforcement of a glider fuselage to incorporate a retractable electric propulsion system is presented as a real-world industrial application.

Experimental investigation of the clinching process for joining the three-layer aluminum/polymer/aluminum composite sheets

Three-layer aluminum/polymer/aluminum composite sheets are among the new materials developed to reduce the weight and fuel consumption of vehicles. Using the conventional methods for joining these materials to other materials is challenging. In this paper, the joinability of the three-layer aluminum/polymer/aluminum to a single-layer 1 mm-thickness aluminum sheet, in the clinching process is investigated. Three-layer sheets of AA5754/polyethylene/AA5754 with thicknesses of 0.5/0.6/0.5 mm were produced under laboratory conditions using two different methods; with and without a local reinforcement piece in the polymer core. The prepared specimens are joined using various geometric parameters of the clinching tools. The joint sections and their geometric parameters including interlock and neck thickness are evaluated in different joint conditions. Also, the strengths of the joints are examined by shear and peel tests. Studies show that it is possible to use the clinching process to join aluminum/polymer/aluminum sheets. Also, with a proper design of tools, the joint strength can be in the same order as the strength of the clinching of single-layer sheets. The maximum shear and peel test strengths, obtained in this study are 1288 N and 540 N, respectively. Increasing the pin penetration depth increases the interlock up to an optimal value. However, further increases in the pin penetration depth will decrease the neck thickness and joint strength. The conical angle of the pin, increasing the die cavity depth, and using a local reinforcement piece reduces the strength of the clinched joint and interlock in these materials. In all the test conditions, the most suitable joint conditions were when the failure mode was combined bottom separation and neck fracture mode.

Structural Optimization Design of Throttle Valve Core for Intelligent Layered Polymer Injection String Controlled By Cable

Optimization Design of Throttling Valve Core Structure for Wired Intelligent Layered Polymer Injection String : Wired intelligent layered polymer in-jection technology can improve the coverage of polymer flooding, alleviate inter-layer conflicts in reservoir development, and improve crude oil recovery. It is an important component of tertiary oil recovery. However, the layered polymer in-jection technology currently used in most domestic oilfields is still the method of fishing and changing the injection nozzle for testing and adjustment. The alloca-tion efficiency of injection volume testing for each layer is slow, with large er-rors, and it is impossible to monitor polymer injection parameters throughout the process. To this end, research has been carried out on the cable controlled intelli-gent layered polymer injection string. By optimizing a highly efficient and low viscosity loss streamlined layered polymer injection throttling device with contin-uously adjustable gaps, the adjustment stroke is shorter and the measurement and adjustment efficiency is higher. Using finite element simulation, the low shear throttle control unit was studied and optimized. By moving the polymer core up and down slightly in the axial direction, the relative gap between the polymer core and the working cylinder was changed to achieve flow adjustment. At the same time, it is necessary to complete the direct reading measurement and adjustment process to form a single pipe layered polymer injection measurement and adjust-ment integration technology. The cable controlled intelligent layered polymer in-jection matching technology connects with the ground intelligent control system through cables to achieve realtime monitoring and online control of polymer flow, pressure, temperature, and other parameters, improving monitoring accura-cy and efficiency, and providing technical support for the construction of the “Digital Intelligence Oilfield”.

Neuroprotective effects of a hemoglobin-based oxygen carrier (stroma-free hemoglobin nanoparticle) on ischemia reperfusion injury

The application of hemoglobin (Hb)-based oxygen carriers (HBOCs) to the treatment of cerebral ischemia has been investigated. A cluster of 1 Hb and 3 human serum albumins (Hb-HSA3) was found to exert neuroprotective effects on ischemia/reperfusion injury. Stroma-free hemoglobin nanoparticles (SFHbNP), a subsequently developed HBOC consisting of a spherical polymerized stroma-free Hb core with a HSA shell, contains the natural antioxidant enzyme catalase and, thus, is expected to exert additive effects. We herein investigated whether SFHbNP exerted enhanced neuroprotective effects in a rat transient middle cerebral artery occlusion (tMCAO) model. Rats were subjected to 2-hour tMCAO and divided into the following 3 groups with the intravenous administration of the respective reagents: (1) phosphate-buffered saline (PBS), as a vehicle (2) Hb-HSA3, and (3) SFHbNP. After 24-hour reperfusion, infarct and edema volumes decreased in the order of the PBS, Hb-HSA3, and SFHbNP groups, with a significant difference (p < 0.05) between the PBS and SFHbNP groups. Similar reductions were observed in oxidative stress, leukocyte recruitment, and blood–brain barrier disruption in the order of the PBS, Hb-HSA3, and SFHbNP groups. In the early phase of reperfusion within 6 h, microvascular HBOC perfusion and cerebral blood flow were maintained at high levels during the reperfusion period in the Hb-HSA3 and SFHbNP groups. However, a difference was observed in tissue oxygen partial pressure levels, which significantly decreased after 6-hour reperfusion in the Hb-HSA3 group, but remained high in the SFHbNP group. A superior oxygen transport ability appears to be related to the enhanced neuroprotective effects of SFHbNP.

Glycan-modified cellular nanosponges for enhanced neutralization of botulinum toxin

Botulinum toxin (BoNT) is a potent neurotoxin that poses a significant threat as a biowarfare weapon and a potential bioterrorist tool. Currently, there is a lack of effective countermeasures to combat BoNT intoxication in the event of a biological attack. Here, we report on a novel solution by combining cell metabolic engineering with cell membrane coating nanotechnology, resulting in the development of glycan-modified cellular nanosponges that serve as a biomimetic and broad-spectrum BoNT detoxification strategy. Specifically, we increase the expression levels of gangliosides on THP-1 cells through metabolic engineering, and then collect the modified THP-1 cell membrane and coat it onto synthetic polymeric cores, creating cellular nanosponges that closely mimic host cells. Our findings demonstrate that higher levels of gangliosides on the cellular nanosponges result in greater binding capacities with BoNT. The glycan-modified cellular nanosponges exhibit superior efficacy in neutralizing BoNT cytotoxicity in vitro when compared to their unmodified counterparts. In a mouse model of BoNT intoxication, the glycan-modified cellular nanosponges show more pronounced survival benefits when administered both as a treatment and a preventative regimen. These results highlight the potential of cellular nanosponges, especially when modified with glycans, as a promising countermeasure platform against BoNT and related clostridial toxins.

Membrane fouling monitoring by 3ω sensing

Membrane fouling significantly reduces membrane permeability, leading to higher operational expenses. In situ monitoring of membrane fouling can potentially be used to reduce operation cost by optimizing operational parameters and cleaning conditions. In this study, a platinum wire with a diameter of 20 µm was attached to the surface of a ceramic ultrafiltration membrane, and by measuring the voltage across the wire while applying an AC current, the amplitude of the third harmonic wave, the so-called 3ω signal, was obtained. Results showed increasing 3ω signals during formation of fouling layers, which correlates directly to the hydraulic resistance of the formed fouling layer in semi-dead end filtration of polymeric core shell particles and crossflow filtration of diluted milk. This is explained by the insulating effect of the fouling layers which reduces heat convection by crossflow and the different thermal conductivity in the fouling layer compared with the feed. After membrane cleaning, the permeability and the magnitude of the 3ω signal were partly restored, showing that the 3ω method can be used to monitor the effect of cleaning. The frequency of the AC current was varied so it was possible to measure the heat conductivity in the fouling layer (high frequency) and heat convection due to cross-flow (low frequency). This may potentially be used to get information of the type of fouling (heat conductivity) and thickness of the fouling layer (AC frequency where heat conductivity becomes dominating).

The Effect Of Polymer Concentration On Coaxial Electrospinning Of Pvp/Pcl Core-Sheath Nanofibers

Core-sheath nanofibers are being developed with coaxial electrospinning for use in drug release studies. In this study, nanofiber structures were developed as hydrophobic PCL in the sheath and hydrophilic PVP in the core. The effect of polymer concentrations on fiber structure and water contact angle was observed by forming two different test groups. In the first group, fiber diameters were observed to decrease depending on viscosity as the polymer concentration decreased from 10% PCL / 10% PVP to 6% PCL / 6% PVP. It was also observed that the contact angle decreased from 104.3° to 57.61° as the concentration decreased. In the second group, the shell polymer ratio was kept constant as 10% wt PCL, while the core polymer ratio was decreased to 10 %, 8% and 6%. It was observed that the core polymer in the structure became hydrophilic as its viscosity decreased. Compared to the first group, the decrease in the contact angles of the surfaces was less since the shell polymer ratio was kept constant. Contact angles decreased from 104.3° to 96.29°.

Development and In Vitro Evaluation of Crizotinib-Loaded Lipid-Polymer Hybrid Nanoparticles Using Box-Behnken Design in Non-small Cell Lung Cancer.

The goal of the study was to produce, optimize, characterize, and compare crizotinib-loaded lipid-polymer hybrid nanoparticles (CL-LPHNPs), representing a novel contribution to the existing literature, and to determine their anticancer activity in non-small cell lung cancer cells (NSCLC). Box-Behnken design was used to investigate the effect of three independent variables: polymer amount (X1), soy phosphatidylcholine (X2), and DSPE-PEG (X3), on three responses: particle size (Y1), polydispersity index (Y2), and zeta potential (Y3). Different parameters were evaluated on the optimized LPHNP formulations such as encapsulation efficiency, drug release study, transmission electron microscopy (TEM) image analysis, and in vitro cell evaluations. The mean particle size of the optimized formulation is between 120 and 220 nm with a PDI<0.2 and a zeta potential of -10 to -15 mV. The encapsulation efficiency values of crizotinib-loaded PLGA-LPHNPs (CL-PLGA-LPHNPs) and crizotinib-loaded PCL-LPHNPs (CL-PCL-LPHNPs) were 79.25±0.07% and 70.93±1.81%, respectively. Drug release study of CL-PLGA-LPHNPs and CL-PCL-LPHNPs showed a controlled and sustained release pattern as a result of core-shell type. Additionally, after 48 h, CL-PLGA-LPHNPs and CL-PCL-LPHNPs significantly reduced the viability of NCI-H2228 cells compared to free crizotinib. Moreover, CL-PLGA-LPHNPs and CL-PCL-LPHNPs exhibited a significant decrease in RAS, RAF, MEK, and ERK gene/protein expression levels after 48-h incubation. In conclusion, this pioneering study introduces lipid-polymer hybrid nanoparticles containing crizotinib as a novel treatment approach, uniting the advantages of a polymeric core and a lipid shell. The successful formulation optimization using Box-Behnken design yielded nanoparticles with adjustable size, remarkable stability, high drug loading, and a customizable drug release profile. Extensive investigations of key parameters, including particle size, PDI, ZP, TEM analysis, drug release, EE%, and in vitro evaluations, validate the potential of these nanoparticles. Moreover, the examination of two different polymers, PLGA and PCL, highlights their distinct impacts on nanoparticle performance. This research opens up new prospects for advanced therapeutic interventions with lipid-polymer hybrid nanoparticles.

A homologous and molecular dual-targeted biomimetic nanocarrier for EGFR-related non-small cell lung cancer therapy.

The abnormal activation of epidermal growth factor receptor (EGFR) drives the development of non-small cell lung cancer (NSCLC). The EGFR-targeting tyrosine kinase inhibitor osimertinib is frequently used to clinically treat NSCLC and exhibits marked efficacy in patients with NSCLC who have an EGFR mutation. However, free osimertinib administration exhibits an inadequate response in vivo, with only ∼3% patients demonstrating a complete clinical response. Consequently, we designed a biomimetic nanoparticle (CMNP@Osi) comprising a polymeric nanoparticle core and tumor cell-derived membrane-coated shell that combines membrane-mediated homologous and molecular targeting for targeted drug delivery, thereby supporting a dual-target strategy for enhancing osimertinib efficacy. After intravenous injection, CMNP@Osi accumulates at tumor sites and displays enhanced uptake into cancer cells based on homologous targeting. Osimertinib is subsequently released into the cytoplasm, where it suppresses the phosphorylation of upstream EGFR and the downstream AKT signaling pathway and inhibits the proliferation of NSCLC cells. Thus, this dual-targeting strategy using a biomimetic nanocarrier can enhance molecular-targeted drug delivery and improve clinical efficacy.

Development and Characterization of Gel-Based Buccoadhesive Bilayer Formulation of Nifedipine.

A promising controlled drug delivery system has been developed based on polymeric buccoadhesive bilayered formulation that uses a drug-free backing layer and a polymeric hydrophilic gel buccoadhesive core layer containing nifedipine. The DSC thermogravimetric analysis confirms the drug's entrapment in the gel layer and reveals no evidence of a potential interaction. Various ratios of bioadhesive polymers, including HPMC K100, PVP K30, SCMC, and CP 934, were combined with EC as an impermeable backing layer to ensure unidirectional drug release towards the buccal mucosa. The polymeric compositions of hydrophilic gel-natured HPMC, SCMC, and CP formed a matrix layer by surrounding the core nifedipine during compression. Preformulation studies were performed for all of the ingredients in order to evaluate their physical and flow characteristics. Ex vivo buccoadhesive strength, surface pH, swelling index, in vitro and in vivo drug release, and ex vivo permeation investigations were performed to evaluate the produced gel-based system. Rapid temperature variations had no appreciable impact on the substance's physical properties, pharmacological content, or buccoadhesive strength during stability testing using actual human saliva. It was clear from a histological examination of the ex vivo mucosa that the developed system did not cause any irritation or inflammation at the site of administration. The formulation NT5 was the best one, with a correlation coefficient of 0.9966. The in vitro and in vivo drug release profiles were well correlated, and they mimic the in vitro drug release pattern via the biological membrane. Thus, the developed gel-based formulation was found to be novel, stable, and useful for the targeted delivery of nifedipine.

Phosphorus-carrying cascade molecules: inner architecture to biomedical applications.

Cascade molecules are nearly uniform-sized macromolecules of small molecules or linear polymer cores built around symmetric branching units. A wide range of biological properties can be achieved with phosphorus-containing dendrimers, depending on their terminal functions, ranging from biomaterials to imaging, drug delivery, and acting as a drug by themselves. This feature article presents significant examples of phosphorus-containing dendrimers used to develop biochips, support cell cultures, carry or deliver biomacromolecules and drugs, bioimaging, and combinational benefits. Because of the thermal stability, ferrocene function, and physical and chemical properties of phosphorus, dendrimers show greater rigidity, mobility, and strength. These dendrimers will be discussed as having a favorable effect on cell growths, especially on neuronal cells, as well as human immune cells like natural killer cells and monocytes, which have a crucial part in preventing cancerous and viral infections. Several phosphorus dendrimers are effective as drugs by themselves (drug per se) and show their activity against neurodegenerative diseases, cancer, inflammation, ocular hypertension, and transmissible spongiform encephalopathies (TSEs) in both in vivo and in vitro. The present review discusses the synthetic route, fabrications, and biomedical applications of phosphorus-containing dendrimers. The toxicity of these dendrimers was also reported.