Synthesis and Self-Assembly of the pH-Responsive Anionic Copolymers for Enhanced Doxorubicin-Loading Capacity.

Polyelectrolyte complex micelles self-assembled from an ionic polymer and oppositely charged small molecules are a promising drug delivery system. In this study, the anionic block copolymers composed of poly(ethylene glycol), poly(ε-caprolactone), and carboxyl modified poly(ε-caprolactone), COOH-PCEC, were designed to encapsulate doxorubicin (DOX) via electrostatic and hydrophobic interactions to form spherical micelles with a particle size of 90-140 nm. The higher payload capacity of these micelles than noncharged micelles of PCL-poly(ethylene glycol)-PCL (PCEC) was achieved, and it was strongly dependent on the composition of the micelles. In vitro drug release studies showed that the release of DOX from the micelles was faster at pH 5.5 than at pH 7.4, which was mainly due to the protonation of carboxyl groups and the solubility of DOX. Studies of intracellular uptake demonstrated that the DOX-loaded micelles could be internalized effectively by HeLa cells. In vitro cytotoxicity revealed that the blank COOH-PCEC micelles had a low cytotoxicity against both L929 and HeLa cells. However, the DOX-loaded micelles inhibited the growth of HeLa cells remarkably, demonstrating their potential for use as an efficient carrier for the delivery of DOX.

Advancing dentin remineralization: Exploring amorphous calcium phosphate and its stabilizers in biomimetic approaches.

OBJECTIVE: This review elucidates the mechanisms underpinning intrafibrillar mineralization, examines various amorphous calcium phosphate (ACP) stabilizers employed in dentin's intrafibrillar mineralization, and addresses the challenges encountered in clinical applications of ACP-based bioactive materials. METHODS: The literature search for this review was conducted using three electronic databases: PubMed, Web of Science, and Google Scholar, with specific keywords. Articles were selected based on inclusion and exclusion criteria, allowing for a detailed examination and summary of current research on dentin remineralization facilitated by ACP under the influence of various types of stabilizers. RESULTS: This review underscores the latest advancements in the role of ACP in promoting dentin remineralization, particularly intrafibrillar mineralization, under the regulation of various stabilizers. These stabilizers predominantly comprise non-collagenous proteins, their analogs, and polymers. Despite the diversity of stabilizers, the mechanisms they employ to enhance intrafibrillar remineralization are found to be interrelated, indicating multiple driving forces behind this process. However, challenges remain in effectively designing clinically viable products using stabilized ACP and maximizing intrafibrillar mineralization with limited materials in practical applications. SIGNIFICANCE: The role of ACP in remineralization has gained significant attention in dental research, with substantial progress made in the study of dentin biomimetic mineralization. Given ACP's instability without additives, the presence of ACP stabilizers is crucial for achieving in vitro intrafibrillar mineralization. However, there is a lack of comprehensive and exhaustive reviews on ACP bioactive materials under the regulation of stabilizers. A detailed summary of these stabilizers is also instrumental in better understanding the complex process of intrafibrillar mineralization. Compared to traditional remineralization methods, bioactive materials capable of regulating ACP stability and controlling release demonstrate immense potential in enhancing clinical treatment standards.

An Intelligent Tongue Diagnosis System via Deep Learning on the Android Platform.

To quickly and accurately identify the pathological features of the tongue, we developed an intelligent tongue diagnosis system that uses deep learning on a mobile terminal. We also propose an efficient and accurate tongue image processing algorithm framework to infer the category of the tongue. First, a software system integrating registration, login, account management, tongue image recognition, and doctor-patient dialogue was developed based on the Android platform. Then, the deep learning models, based on the official benchmark models, were trained by using the tongue image datasets. The tongue diagnosis algorithm framework includes the YOLOv5s6, U-Net, and MobileNetV3 networks, which are employed for tongue recognition, tongue region segmentation, and tongue feature classification (tooth marks, spots, and fissures), respectively. The experimental results demonstrate that the performance of the tongue diagnosis model was satisfying, and the accuracy of the final classification of tooth marks, spots, and fissures was 93.33%, 89.60%, and 97.67%, respectively. The construction of this system has a certain reference value for the objectification and intelligence of tongue diagnosis.

Amphiphilic block polymer-based self-assembly of high payload nanoparticles for efficient combinatorial chemo-photodynamic therapy.

Combinatorial chemo-photodynamic therapy is regared as effective cancer therapy strategy, which could be realized via multiple nano-drug delivery system. Herein, novel high payload nanoparticles stabilized by amphiphilic block polymer cholesterol-b-poly(ethylene glycol) (PEG)2000 (Chol-PEG2000) were fabricated for loading chemotherapeutic drug 10-hydroxycamptothecin (HCPT) and photosensitizer chlorin e6 (Ce6). The obtained HCPT/Ce6 NPs showed uniform rod-like morphology with a hydration diameter of 178.9 ± 4.0 nm and excellent stability in aqueous solution. HCPT and Ce6 in the NPs displayed differential release profile, which was benefit for preferentially exerting the photodynamic effect and subsequently enhancing the sensitivity of the cells to HCPT. Under laser irradiation, the NPs demonstrated fantastic in vitro and in vivo anticancer efficiency due to combinational chemo-photodynamic therapy, enhanced cellular uptake effectiveness, and superb intracellular ROS productivity. Besides, the NPs were proved as absent of systemic toxicity. In summary, this nanoparticle delivery system could be hopefully utilized as effective cancer therapy strategy for synergistically exerting combined chemo-photodynamic therapy in clinic.

Effect of different sterilization methods on the properties of commercial biodegradable polyesters for single-use, disposable medical devices.

The increasing employment of non-degradable polymers based single-use, disposable medical devices have led to huge environmental pressure. Replacement of non-degradable polymers with biodegradable alternatives could be one solution. Since terminal sterilization is a necessary procedure for medical devices to eliminate infections, in this paper, the modifications of sterilization on the transparency, yellow index, dimensional stability and mechanical properties of commercial biodegradable poly(lactic acid) (PLA), poly(butylenes adipate-co-terephthalate) (PBAT) and their blends were investigated. The samples were prepared by compression molding and exposed to four sterilization treatments including ethylene oxide gas (EtO), saturated steam (SS), electron beam (EB), and hydrogen peroxide gas plasma (HPGP). It is concluded that EB can be applied for the sterilization of all the materials investigated, while SS and EtO are not recommended for PLA, and HPGP is not for PBAT and PLA/PBAT blends. This study demonstrates that, when a suitable sterilization process is chosen, PLA has potential to be used for transparent medical devices such as the barrel of syringes or microfluidic chips, while PBAT and PLA/PBAT blends for other non-transparent medical packaging applications.

An organic solvent-free technology for the fabrication of albumin-based paclitaxel nanoparticles for effective cancer therapy.

Organic solvents have been reported to exert certain influence on the structure and drug loading efficiency of albumin. It is urgent to develop organic solvent-free albumin-based paclitaxel nanoparticles for effective anticancer therapy. In this study, novel PTX liposome-albumin composite nanoparticles (Lip-PTX/BSA NPs) aimed at avoiding the direct contact of albumin with toxic organic solvents and enhancing the colloidal stability of the formulation were prepared. To methodically evaluate the impacts of multifarious factors on the critical characteristics of the nanoparticles, Box-Behnken design was applied in the formulation optimized process. Ratio of drug-phosphatidylcholine (EPC), ratio of drug-BSA and pH of the media were chosen as the independent variables, while particle size and drug-loading content (DLC) loss rate were applied as the selected response variables. A quadratic model fitted best to describe the data with maximal lack-of-fit p-value and minimum sequential p-value. Three-dimension surface figures were utilized to describe the correlation of independent variables with response variables. Optimized formulation of the nanoparticles with size of 116.2 ±â€¯2.0 nm and zeta potential of -18.4 ±â€¯1.01 mV were obtained with a high encapsulation efficiency of 99.8%. PTX was involved physical interaction with the excipient during the preparation process of the nanoparticles. The release of PTX from Lip-PTX/BSA NPs exhibited a sustained release manner compared to albumin-bound PTX (nab-PTX) and Taxol. Besides, Lip-PTX/BSA NPs presented enhanced in vitro cytotoxicity against 4T1 cells due to highly nonspecific internalization in the cytoplasm. Simultaneously, Lip-PTX/BSA NPs showed effective in vivo antitumor efficacy against 4T1 bearing BALB/c mice, while no apparent adverse effect was observed by histological section and blood biochemical analysis. In conclusion, the novel Lip-PTX/BSA NPs could be applied as a promising drug delivery system for PTX to exert efficient cancer curative effects in clinic.

"Smart" chemistry and its application in peroxidase immobilization using different support materials.

In the past few decades, the enzyme immobilization technology has been exploited a lot and thus became a matter of rational design. Immobilization is an alternative approach to bio-catalysis with the added benefits, adaptability to automation and high-throughput applications. Immobilization-based approaches represent simple but effective routes for engineering enzyme catalysts with higher activities than wild-type or pristine counterparts. From the chemistry viewpoint, the concept of stabilization via manipulation of functional entities, the enzyme surfaces have been an important driving force for immobilizing purposes. In addition, the unique physiochemical and structural functionalities of pristine or engineered cues, or insoluble support matrices (carrier) such as mean particle diameter, swelling behavior, mechanical strength, and compression behavior are of supreme interest and importance for the performance of the immobilized systems. Immobilization of peroxidases into/onto insoluble support matrices is advantageous for practical applications due to convenience in handling, ease separation of enzymes from a reaction mixture and the reusability. A plethora of literature is available explaining individual immobilization system. However, current literature lacks the chemistry viewpoint of immobilization. This review work presents state-of-the-art "Smart" chemistry of immobilization and novel potentialities of several materials-based cues with different geometries including microspheres, hydrogels and polymeric membranes, nanoparticles, nanofibers, composite and hybrid or blended support materials. The involvement of various functional groups including amino, thiol, carboxylic, hydroxyl, and epoxy groups via "click" chemistry, amine chemistry, thiol chemistry, carboxyl chemistry, and epoxy chemistry over the protein surfaces is discussed.

Genome shuffling of Aspergillus glaucus HGZ-2 for enhanced cellulase production.

The production of cellulase from Aspergillus glaucus HGZ-2 was improved by using genome shuffling. The starting populations, obtained by UV irradiation, were subjected to recursive protoplast fusion. The optimal conditions for protoplast formation and regeneration were 7 mg/ml snailase and 5 mg/ml cellulase at 34 °C for 3.0 h using 0.7 M NaCl as an osmotic stabilizer. The protoplasts were inactivated under UV for 30 min or heated at 50 °C for 50 min, and a fusant probability of about 100 % was observed. The positive colonies were created by fusing the inactivated protoplasts. The optimal conditions for protoplast fusion were PEG6000 concentration of 35 %, CaCl2 concentration of 0.02 M, and incubation time of 12 min. After two rounds of genome shuffling, one strain (Y) was obtained. Its filter paper cellulase (FPase) and carboxymethyl cellulase (CMCase) activity reached 71 and 70 U/ml, respectively, which were increased by 1.95-fold and 1.72-fold in comparison with that of its ancestor strain. The results indicated that genome shuffling was an efficient means for the improved production of cellulases by A. glaucus HGZ-2.