Preparation of self-assembly silica redox nanoparticles to improve drug encapsulation and suppress the adverse effect of doxorubicin.

Background and Purpose: The utilization of doxorubicin (DOX) in clinal trials is also challenging owing to its adverse effects, including low oral bioavailability, generation of reactive oxygen species (ROS), cardiotoxicity, and epithelial barrier damage. Recently, scavenging of ROS reduced the cytotoxicity of DOX, suggesting a new approach for using DOX as an anticancer treatment. Thus, in this study, non-silica and silica redox nanoparticles (denoted as RNPN and siRNP, respectively) with ROS scavenging features have been designed to encapsulate DOX and reduce its cytotoxicity. Experimental Approach: DOX-loaded RNPN (DOX@RNPN) and DOX-loaded siRNP (DOX@siRNP) were prepared by co-dissolving DOX with RNPN and siRNP, respectively. The size and stability of nanoparticles were characterized by the dynamic light scattering system. Additionally, encapsulation efficiency, loading capacity, and release profile of DOX@RNPN and DOX@siRNP were identified by measuring the absorbance of DOX. Finally, the cytotoxicity of DOX@RNPN and DOX@siRNP against normal murine fibroblast cells (L929), human hepatocellular carcinoma cells (HepG2), and human breast cancer cells (MCF-7) were also investigated. Key results: The obtained result showed that RNPN exhibited a pH-sensitive character while silanol moieties improved the stability of siRNP in physiological conditions. DOX@RNPN and DOX@siRNP were formed at several tens of nanometers in diameter with narrow distribution. Moreover, DOX@siRNP stabilized under different pH buffers, especially gastric pH, and improved encapsulation of DOX owing to the addition of silanol groups. DOX@RNPN and DOX@siRNP maintained anticancer activity of DOX against HepG2, and MCF-7 cells, while their cytotoxicity on L929 cells was significantly reduced compared to free DOX treatment. Conclusion: DOX@RNPN and DOX@siRNP could effectively suppress the adverse effect of DOX, suggesting the potential to become promising nanomedicines for cancer treatments.

Cell membrane-based nanomaterials for therapeutics of neurodegenerative diseases.

Central nervous system (CNS) diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), glioblastoma (GBM), and peripheral nerve injury have been documented as incurable diseases, which lead to serious impacts on human health especially prevalent in the aging population worldwide. Most of the treatment strategies fail due to low efficacy, toxicity, and poor brain penetration. Recently, advancements in nanotechnology have helped alleviate the challenges associated with the application of cell membrane-based nanomaterials against CNS diseases. In the following review, the existing types of cell membrane-based nanomaterials systems which have improved therapeutic efficacy for CNS diseases would be described. A summary of recent progress in the incorporation of nanomaterials in cell membrane-based production, separation, and analysis will be provided. Addition to, challenges relate to large-scale manufacturing of cell membrane-based nanomaterials and future clinical trial of such platforms will be discussed.

SALAD: Syringe-based Arduino-operated Low-cost Antibody Dispenser.

Lateral Flow Assays (LFA) have been one of the most widely adopted technologies in clinical diagnosis over recent years, especially during the COVID-19 pandemic, due to their feasibility, compactness, and rapid readout. However, the precise dispensing of antibodies-a key part of the fabrication process-requires costly line dispenser equipment, which poses a challenge to researchers with limited budgets. This study aims to resolve this key issue by introducing a Syringe-based Arduino-operated Low-cost Antibody Dispenser (SALAD). By utilizing a microneedle, stepper motor-driven syringe pump, and conveyor belt, SALAD can form micro-droplets to create an even band of antibodies. Our evaluation results showed comparable performance between SALAD and a commercialized model - Claremont ALFRD, with SALAD exceeding in affordability and feasibility. SALAD yielded an even signal, uniform bandwidth, and low background noise, yet optimization in the conveyor belt should be considered to enhance stability. With a low manufacturing cost ($200.61) compared to the commercialized models, our model is expected to provide an affordable approach for LFA researchers.

Optimization of Oligomer Chitosan/Polyvinylpyrrolidone Coating for Enhancing Antibacterial, Hemostatic Effects and Biocompatibility of Nanofibrous Wound Dressing.

A synergistic multilayer membrane design is necessary to satisfy a multitude of requirements of an ideal wound dressing. In this study, trilayer dressings with asymmetric wettability, composed of electrospun polycaprolactone (PCL) base membranes coated with oligomer chitosan (COS) in various concentrations of polyvinylpyrrolidone (PVP), are fabricated for wound dressing application. The membranes are expected to synergize the hygroscopic, antibacterial, hemostatic, and biocompatible properties of PCL and COS. The wound dressing was coated by spraying the solution of 3% COS and 6% PVP on the PCL base membrane (PVP6-3) three times, which shows good interaction with biological subjects, including bacterial strains and blood components. PVP6-3 samples confirm the diameter of inhibition zones of 20.0 ± 2.5 and 17.9 ± 2.5 mm against Pseudomonas aeruginosa and Staphylococcus aureus, respectively. The membrane induces hemostasis with a blood clotting index of 74% after 5 min of contact. In the mice model, wounds treated with PVP6-3 closed 95% of the area after 10 days. Histological study determines the progression of skin regeneration with the construction of granulation tissue, new vascular systems, and hair follicles. Furthermore, the newly-growth skin shares structural resemblances to that of native tissue. This study suggests a simple approach to a multi-purpose wound dressing for clinical treatment.

The Efficacy of Silver-Based Electrospun Antimicrobial Dressing in Accelerating the Regeneration of Partial Thickness Burn Wounds Using a Porcine Model.

(1) Background: Wounds with damages to the subcutaneous are difficult to regenerate because of the tissue damages and complications such as bacterial infection. (2) Methods: In this study, we created burn wounds on pigs and investigated the efficacy of three biomaterials: polycaprolactone-gelatin-silver membrane (PCLGelAg) and two commercial burn dressings, Aquacel® Ag and UrgoTulTM silver sulfadiazine. In vitro long-term antibacterial property and in vivo wound healing performance were investigated. Agar diffusion assays were employed to evaluate bacterial inhibition at different time intervals. Minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and time-kill assays were used to compare antibacterial strength among samples. Second-degree burn wounds in the pig model were designed to evaluate the efficiency of all dressings in supporting the wound healing process. (3) Results: The results showed that PCLGelAg membrane was the most effective in killing both Gram-positive and Gram-negative bacteria bacteria with the lowest MBC value. All three dressings (PCLGelAg, Aquacel, and UrgoTul) exhibited bactericidal effect during the first 24 h, supported wound healing as well as prevented infection and inflammation. (4) Conclusions: The results suggest that the PCLGelAg membrane is a practical solution for the treatment of severe burn injury and other infection-related skin complications.

Characterizations and Antibacterial Efficacy of Chitosan Oligomers Synthesized by Microwave-Assisted Hydrogen Peroxide Oxidative Depolymerization Method for Infectious Wound Applications.

The use of naturally occurring materials with antibacterial properties has gained a great interest in infected wound management. Despite being an abundant resource in Vietnam, chitosan and its derivatives have not yet been intensively explored for their potential in such application. Here, we utilized a local chitosan source to synthesize chitosan oligomers (OCS) using hydrogen peroxide (H2O2) oxidation under the microwave irradiation method. The effects of H2O2 concentration on the physicochemical properties of OCS were investigated through molecular weight, degree of deacetylation, and heavy metal contamination for optimization of OCS formulation. Then, the antibacterial inhibition was examined; the minimum inhibitory concentration and minimum bactericidal concentration (MIC and MBC) of OCS-based materials were determined against common skin-inhabitant pathogens. The results show that the local Vietnamese chitosan and its derivative OCS possessed high-yield purification while the molecular weight of OCS was inversely proportional and proportional to the concentration of H2O2, respectively. Further, the MIC and MBC of OCS ranged from 3.75 to less than 15 mg/mL and 7.5-15 mg/mL, respectively. Thus, OCS-based materials induce excellent antimicrobial properties and can be attractive for wound dressings and require further investigation.

The effect of oxidation degree and volume ratio of components on properties and applications of in situ cross-linking hydrogels based on chitosan and hyaluronic acid.

The purpose of this research is to investigate the effect of different oxidation degrees and volume ratios of components on the physical properties and biocompatibility of an in situ cross-linking chitosan-hyaluronic acid-based hydrogel for skin wound healing applications. Carboxymethyl groups (-CH2COOH) were introduced to the polymer chain of chitosan, producing N,O - Carboxymethyl Chitosan (NOCC). Hyaluronic acid was oxidized to obtain aldehyde hyaluronic acid (AHA) with three oxidation degrees (AHA40, AHA50 and AHA60). The gelation was induced by forming Schiff base linkage between aldehyde groups of AHA and amino groups of NOCC. Then, the polysaccharide derivatives were combined at three NOCC:AHA volume ratios (3:7, 5:5 and 7:3) to form composite hydrogels without using any additional cross-linker. FT-IR analysis, surface morphology observation and wettability test, in vitro degradation test and rheological analysis were carried out to characterize the hydrogels. Additionally, in vitro cytotoxicity and in vivo wound healing evaluations were also conducted to study the biocompatibility of the composite. Our findings showed that when increasing the volume of NOCC, the homogeneity and hydrophobicity of the resulting hydrogels were also improved and their pore walls became thicker, leading to slower degradation rate. On the other hand, when raising the oxidation degree of AHA, the hydrophilicity of the gels decreased and less time was required to form the gel matrix. Besides, the obtained in vitro and in vivo results indicated that lower oxidation degree of AHA supports cell proliferation, cell attachment and wound healing process better. It is also concluded that NOCC-AHA40 5:5 hydrogel is most suitable for skin wound healing applications since it possesses superior morphology with high uniformity, favorable pore size and suitable density along with appropriate wettability. The NOCC-AHA gel matrix is expected to be used as a delivery system for other factors and employed as an effective bio-glue in further tissue engineering applications.

Characterization of healthy and nonmelanoma-induced mouse utilizing the Stokes-Mueller decomposition.

Skin cancer is one of the most common cancers, including melanoma and nonmelanoma cancer. Melanoma can be easily detected by the observation of abnormal moles, but nonmelanoma signs and symptoms are not apparent in the early stages. We use the Stokes-Mueller matrix decomposition method to detect nonmelanoma at the early stage by decomposing the characteristics of polarized light interacting with normal and cancerous tissues. With this decomposition method, we extract nine optical parameters from biological tissues, namely the LB orientation angle (α), the LB phase retardance (ß), the CB optical rotation angle (γ), the LD orientation angle (θd), the linear dichroism (D), the circular dichroism (R), the degrees of linear depolarization (e1 and e2), the degree of circular depolarization (e3), and the depolarization index (Δ). The healthy skin and the induced nonmelanoma skin cancer of mice are analyzed and compared based on their optical parameters. We find distinctive ranges of values for normal skin tissue and nonmelanoma skin cancer, in which ß and D in cancerous tissue are larger and nonmelanoma skin becomes less depolarized. This research creates an innovative solid foundation for the diagnosis of skin cancer in the future.

Optical parameters of human blood plasma, collagen, and calfskin based on the Stokes-Mueller technique.

A decoupled analytical technique based on the Stokes-Mueller matrix decomposition method extracts polarization properties of human blood plasma, collagen solution, and calfskin. The proposed method is applied initially to extract the nine effective optical parameters of human blood plasma samples containing D-glucose powder with concentrations ranging from 0-1 M. The optical rotation angle of circular birefringence (CB) increases linearly with the glucose concentration in human blood plasma samples (r2=0.9782) and in tissue phantom samples (r2=0.9939). Meanwhile, the phase retardance of linear birefringence (LB) increases slightly from 0° to almost 2° as the D-glucose concentration increases. However, for the plasma samples, the optical rotation angle increases by 1.07±0.1 deg for each additional mole of D-glucose, while, for the tissue phantom samples, the optical rotation angle increases by 0.75±0.1 deg. For collagen solutions with concentrations ranging from 0 to 2 mg/mL, a strong linear relationship (r2=0.9936) is observed between the phase retardance of linear birefringence and the collagen concentration. Finally, for the calfskin samples, the linear birefringence reduces exponentially (r2=0.9689) over time following collagenase treatment. Overall, the decoupled analytical model provides a reliable and straightforward technique for detecting the optical properties of laboratory and natural biological samples. As a result, it has significant potential for diagnostic applications and the structural analysis of biological tissues.

Encapsulation of Solid Dispersion in Solid Lipid Particles for Dissolution Enhancement of Poorly Water-Soluble Drug.

BACKGROUND: The aim of this research was to engineer solid dispersion lipid particles (SDSLs) in which a solid dispersion (SD) was encapsulated to form the core of solid lipid particles (SLs), thereby achieving an efficient enhancement in the dissolution of a poorly water-soluble drug. METHODS: Ultrasonication was introduced into the process to obtain micro/nanoscale SLs. The mechanism of dissolution enhancement was investigated by analysing the crystalline structure, molecular interactions, and particle size of the formulations. RESULTS: The drug release from the SD-SLs was significantly greater than that from the SD or SLs alone. This enhancement in drug release was dependent on the preparation method and the drug-topolymer ratio of the SD. With an appropriate amount of polymer in the SD, the solidification method had the potential to alter the drug crystallinity to an amorphous state, resulting in particle uniformity and molecular interactions in the SD-SLs. CONCLUSIONS: The proposed system provides a new strategy for enhancing the dissolution rate of poorly water-soluble drugs and further improving their bioavailability.

Investigate the Effect of Thawing Process on the Self-Assembly of Silk Protein for Tissue Applications.

Biological self-assembly is a process in which building blocks autonomously organize to form stable supermolecules of higher order and complexity through domination of weak, noncovalent interactions. For silk protein, the effect of high incubating temperature on the induction of secondary structure and self-assembly was well investigated. However, the effect of freezing and thawing on silk solution has not been studied. The present work aimed to investigate a new all-aqueous process to form 3D porous silk fibroin matrices using a freezing-assisted self-assembly method. This study proposes an experimental investigation and optimization of environmental parameters for the self-assembly process such as freezing temperature, thawing process, and concentration of silk solution. The optical images demonstrated the possibility and potential of -80ST48 treatment to initialize the self-assembly of silk fibroin as well as controllably fabricate a porous scaffold. Moreover, the micrograph images illustrate the assembly of silk protein chain in 7 days under the treatment of -80ST48 process. The surface morphology characterization proved that this method could control the pore size of porous scaffolds by control of the concentration of silk solution. The animal test showed the support of silk scaffold for cell adhesion and proliferation, as well as the cell migration process in the 3D implantable scaffold.

Strategies of Engineering Nanoparticles for Treating Neurodegenerative Disorders.

BACKGROUND: Neurodegenerative disorders (NDs) are typically referred to Alzheimer's disease, Parkinson's diseases, amyotrophic lateral sclerosis and prion disease. These are commonly debilitating and, unfortunately, have few therapeutic options. OBJECTIVE: In this review, we describe some emerging advances in nanoengineering strategies for the treatment of NDs. One of the main difficulties in fighting against NDs is to overcome the shielding of blood-brain barrier (BBB), which greatly limits the penetration of various therapeutic drugs, which sometimes leads to severe side effects. Nanotechnology, by engineering materials of a size scale usually within 1-100 nm, fortunately offers an alternative approach for novel, promising and innovative solutions. Nanoparticles are capable of not only penetrating the BBB but also releasing active ingredients at a specific site due to its surface functionalization. Therefore, nanoengineered delivery systems potentially facilitate the targeted delivery of neuronal therapeutic drugs and genes to the central nervous system. Furthermore, recently developed nanomaterials are considered as therapeutic agents themselves since they exhibit important roles in promoting the protection of healthy neurons or the regeneration of neurons to repair damaged tissues. CONCLUSION: There have been a variety of innovative approaches to designing therapeutic nanoparticles for NDs, and each has been associated with certain pros and cons.

Sonication-Assisted Nanoprecipitation in Drug Delivery.

Sonication-assisted nanoprecipitation provides an effective tool for nanomedicine engineering in therapeutic improvement. In the scope of this review, original works in interdisciplinary areas of using sonication with precipitation method for nanoparticulate drug delivery systems and its applications in management of different diseases are discussed. The use of sonication-assisted nanoprecipitation has been proved to improve drug bioavailability, which attracts tremendous interests as an effective strategy for drug delivery. However, many challenges still remain. To overcome these barriers, different approaches such as precipitation method, rational design, optimization and modification have been investigated. Accordingly, current knowledge of sonication-assisted nanoprecipitation proposes a broad perspective and optimization for the applications of nanotechnology in drug delivery.

Impact of shear stress on Src and focal adhesion kinase phosphorylation in fibrinogen-adherent platelets.

: Shear stress alone can activate platelets resulting in a subsequent platelet aggregation, so-called 'shear-induced platelet aggregation'. In our work, we analyzed how differently elevated shear stress impacts the Src and focal adhesion kinase (FAK) activation in fibrinogen-adherent human platelets. We detected the extents of Src pY418 and FAK pY397 activations in platelets on immobilized fibrinogen and over BSA under shear conditions. Moreover, we analyzed the role of αIIbß3 in the shear-induced platelet signaling by performing our experiments in the presence of the αIIbß3-antagonist Abciximab. Abnormally high shear rates (5000 s) significantly increased the extent of phosphorylation of both tyrosine kinases after short (2 min) incubation time independently of the presence or absence of the integrin αIIbß3 ligand, fibrinogen. We could see considerably greater Src activation on immobilized fibrinogen than on BSA, but the extent of FAK Y397 phosphorylation was independent on the matrix. Abciximab not only reduced the Src and FAK signaling in platelets exposed to 5000 s on immobilized fibrinogen, but in platelets exposed to 5000 s over BSA as well. Our data indicate that whereas Src activation under shear stress is dominantly ligand-dependent, FAK signaling seems to be mostly shear induced.

Design of Fucoidan Functionalized - Iron Oxide Nanoparticles for Biomedical Applications.

This research aims to develop an iron oxide nanoparticle drug delivery system utilizing a recent material discovered from ocean, fucoidan. The material has drawn much interest due to many biomedical functions that have been proven for human health. One interesting point herein is that fucoidan is not only a sulfated polysaccharide, a polymer for stabilization of iron oxide nanoparticles, but plays a role of an anticancer agent also. Various approaches were investigated to optimize the high loading efficiency and explain the mechanism of nanoparticle formations. Fucoidan was functionalized on iron oxide nanoparticles by a direct coating or via amine groups. Also, a hydrophobic part of oleic acid was conjugated to the amine groups for a more favorable loading of poorly water-soluble anticancer drugs. This study proposed a novel system and an efficient method to functionalize fucoidan on iron oxide nanoparticle systems which will lead to a facilitation of a double strength treatment of cancer.

Perspectives of Engineered Marine Derived Polymers for Biomedical Nanoparticles.

Marine environment exhibits an enormous diversity of organisms which contains an abundant source of polysaccharides. As polymer matrix carriers, marine-based polymers possess several valuable properties including high stability, non-toxicity, hydrophilicity, biodegradability, with low production cost. Despite notable biological activities of these natural polymers, there are certain limitations in exploring their functions in applications of nano-sized drug delivery systems. The review aims to demonstrate exceptional characteristics of marine-based polymers including fucoidan, alginate, carrageenan, hyaluronic acid, chondroitin sulfate, and chitosan as well as provide perspectives of current publications on their nanoparticle formulations for biomedical applications.

Development of a modified - solid dispersion in an uncommon approach of melting method facilitating properties of a swellable polymer to enhance drug dissolution.

The study aimed to develop a modified-solid dispersion method using a swellable hydrophilic polymers accompanied by a conventional carrier to enhance the dissolution of a drug that possesses poor water solubility. Two swellable polymers (hydroxypropyl methylcellulose and polyethylene oxide) were swelled in melted polyethylene glycol 6000 (PEG 6000) in different ratios and under different conditions. The type, amount, and, especially, incorporation method of the swellable polymers were crucial factors affecting the dissolution rate, crystallinity, and molecular interaction of the drug. Interestingly, the method in which the swellable polymer was thoroughly mixed with the melted PEG 6000 as the first step was more effective in increasing drug dissolution than the method in which the drug was introduced to the melted PEG 6000 followed by the addition of the swellable polymer. This system has potential for controlling drug release due to high swelling capabilities of these polymers. Therefore, the current study can be considered to be a promising model for formulations of controlled release systems containing solid dispersions.

Design of sustained release tablet containing fucoidan.

The study introduced a new therapeutic agent, fucoidan, which can offer potential medical treatments including anti-inflammatory and anti-coagulant activities, as well as anti-proliferative effects on cancer cells. Fucoidan was included in sustained release formulations expected for an effective plasma drug concentration for approximately 24 h. The matrices based on the two polymers hydroxypropyl methycellulose (HPMC) and polyethylene oxide (PEO) were prepared with various ratios between the polymers and fucoidan. The dissolution profiles of various matrix tablets performed in enzyme-free simulated intestinal fluid (pH 6.8) for 24 h indicated a higher potential of PEO-based matrix tablets in sustaining release of fucoidan. The swelling and erosion of the tablets were also characterized to elucidate the difference among those dissolution profiles.

Amorphous isradipine nanosuspension by the sonoprecipitation method.

The aims of this study are to increase and explain the mechanism of dissolution enhancement of isradipine using the sonoprecipitation method for stable nanosuspensions. There have been still few of published researches on formulation of isradipine using nanoparticle engineering. Nanosuspension systems were prepared upon various factors including amplitude and the time length of ultrasonication. The dissolution test was performed according to the USP paddle method in intestinal fluid (pH 6.8). The crystalline structure of drug, the molecular interaction, morphology and size of nanosuspension were also investigated to determine the mechanism of dissolution enhancement. The sonoprecipitation method with use of HPMC 6 showed its potential in enhancement of the drug release rate. Stable nanosuspension was significantly depended on amplitude and time of ultrasonication since these factors affected on the size of nanoparticles. The synergistic effects of reduction of drug crystallinity and particle size could increase the dissolution rate of isradipine by providing a stable nanosuspension. This work may contribute to a new strategy for improvement dissolution rate of isradipine.

Polymer conjugate-based nanomaterials for drug delivery.

The structure of polymeric amphiphiles with both hydrophilic and hydrophobic groups forming self-assembled nanoparticles have attracted increasing attention in studies of delivery systems of therapeutic agents. An amphiphilic carrier for self-assembly in an aqueous solution is preferable because of its structure with a hydrophobic core and hydrophilic outer shell, which can be applied to many biotechnological and pharmaceutical fields with numerous types of drugs. An amphiphilic carrier for self-assembly also represents the most appealing delivery system owing to its exceptional advantages in selectively delivering drugs to tumor cells and thus, reduction of side effects. This paper reviews two types of self-assembled nanoparticles/micelles of conjugated polymeric amphiphiles: (1) self-assembled micelles/nanoparticles of amphiphilic conjugates followed by drug loading and (2) self-assembled micelles/nanoparticles of polymer-drug conjugates where a conjugation reaction occurs between the polymer and drug. The development of the research has been addressed in this review with up-to-date references. In conclusion, the challenges and remaining difficulties for the future development are discussed.