Review of studies on polysaccharides, lignins and small molecular compounds from three Polygonatum Mill. (Asparagaceae) spp. in crude and processed states.

Since ancient times, Polygonatum Mill. (Asparagaceae) has been utilized as a medicinal and culinary resource in China. Its efficacy in treating various illnesses has been well documented. Traditional processing involves the Nine-Steam-Nine-Bask method, which results in a reduction of toxicity and enhanced effectiveness of Polygonatum. Many substances, such as polysaccharides, lignins, saponins, homoisoflavones, alkaloids, and others, have been successfully isolated from Polygonatum. This review presents the research progress on the chemical composition of three crude and processed Polygonatum, including Polygonatum sibiricum Redouté (P. sibiricum), Polygonatum kingianum Collett & Hemsl (P. kingianum), and Polygonatum cyrtonema Hua (P. cyrtonema). The review also includes the pharmacology of Polygonatum, specifically on the pharmacology of polysaccharides both before and after processing. Its objective is to provide a foundation for uncovering the significance of the processing procedure, and to facilitate the development and utilization of Polygonatum in clinical practice.

Near-Infrared Responsive Biomimetic Titanate/TiO2-X Heterostructure: A Therapeutic Strategy for Combating Implant-Associated Infection and Enhancing Osseointegration.

Implant-associated infections and delayed osseointegration are major challenges for the clinical success of titanium implants. To enhance antibacterial effects and promote early osseointegration, we developed a synergistic photothermal (PTT)/photodynamic (PDT) therapy strategy based on near-infrared (NIR) responsive biomimetic micro/nano titanate/TiO2-X heterostructure coatings (KMNW and NaMNS) in situ constructed on the surface of titanium implants. Specifically, KMNW and NaMNS significantly enhanced photothermal conversion capabilities, achieving localized high temperatures of 48-51 °C and promoting substantial amounts of reactive oxygen species production under 808 nm irradiation. In vitro antibacterial experiments demonstrated that KMNW achieved the highest antibacterial rates against Staphylococcus aureus and Escherichia coli, at 98.78 and 98.33% respectively. Moreover, by mimicking the three-dimensional fibrous network of the extracellular matrix during bone healing, both KMNW and NaMNS markedly promoted the proliferation and osteogenic differentiation of osteoblasts. In vivo implantation studies further confirmed these findings, with KMNW and NaMNS exhibiting superior antibacterial performance under NIR irradiation─94.45% for KMNW and 92.66% for NaMNS. Moreover, KMNW and NaMNS also significantly promoted new bone formation and improved osseointegration in vivo. This study presents a promising PTT/PDT therapeutic strategy for dentistry and orthopedics by employing NIR-responsive biomimetic coatings to combat implant-associated infection and accelerate osseointegration.

Mussel byssus-inspired dual-functionalization of zirconia dental implants for improved bone integration.

Zirconia faces challenges in dental implant applications due to its inherent biological inertness, which compromises osseointegration, a critical factor for the long-term success of implants that rely heavily on specific cell adhesion and enhanced osteogenic activity. Here, we fabricated a dual-functional coating that incorporates strontium ions, aimed at enhancing osteogenic activity, along with an integrin-targeting sequence to improve cell adhesion by mussel byssus-inspired surface chemistry. The results indicated that although the integrin-targeting sequence at the interface solely enhances osteoblast adhesion without directly increasing osteogenic activity, its synergistic interaction with the continuously released strontium ions from the coating, as compared to the release of strontium ions alone, significantly enhances the overall osteogenic effect. More importantly, compared to traditional polydopamine surface chemistry, the coating surface is enriched with amino groups capable of undergoing various chemical reactions and exhibits enhanced stability and aesthetic appeal. Therefore, the synergistic interplay between strontium and the functionally customizable surface offers considerable potential to improve the success of zirconia implantation.

Preparation of olmesartan medoxomil solid dispersion with sustained release performance by mechanochemical technology.

Hypertension is a common disease for human with high morbidity and mortality, and olmesartan medoxomil (OM) is widely used in the therapy of hypertension. However, poor water solubility and low bioavailability limit its widespread use. To improve the effect of OM, a ternary OM solid dispersion consisting of hydroxypropyl-ß-cyclodextrin (HP-ß-CD) and hydroxypropyl methylcellulose (HPMC) was prepared by mechanochemical method. The best preparation parameters were OM/HP-ß-CD/HPMC-E5 with mass ratio of 1:2.6:1 and milling time of 4 h. Under the optimal preparation conditions, the solubility of the ternary solid dispersion could be increased by 12 times as compared with pure OM. Due to the addition of HPMC-E5, the solid dispersion had sustained release performance with prolonged release time of 12 h. Furthermore, in vivo study demonstrated that the prepared solid dispersion could afford significantly improved bioavailability of ~ 3-fold in comparison with pure drug. Hence, the prepared ternary solid dispersion of OM may be a promise delivery system for clinical application.

In vitro release, ex vivo penetration, and in vivo dermatokinetics of ketoconazole-loaded solid lipid nanoparticles for topical delivery.

The study focused to evaluate and investigate optimized (using QbD) and novel ketoconazole (KTZ)-loaded solid lipid nanoparticles (KTZ-SLNs; 2% w/v KTZ) for enhanced permeation across skin. KTZ-SLNs were evaluated for size, distribution, zeta potential (ZP), percent entrapment efficiency (%EE), drug release, morphology (HRTEM and FESEM), thermal behaviour (DSC), spectroscopic (FTIR), and solid-state/diffraction characterization (X-ray diffraction, XRD). Moreover, ex vivo permeation and drug deposition into rat skin were conducted using Franz diffusion cell. The same was confirmed using human dermatome skin and fluorescence, confocal Raman, and vibrational ATR-FTIR microscopic methods. An in vivo dermatokinetics study was performed in rats to assess the extent of KTZ permeation into the skin. Stability including accelerated and photostability studies were conducted at different temperatures (2-8, 30, and 40 °C) for 12 months. The spherical, optimized KTZ-SLN formulation (KOF1) showed particle size of 293 nm and high EE of 88.5%. Results of FTIR, DSC, and XRD confirmed formation of KTZ-SLNs and their amorphous nature due to presence of KTZ in a dissolved state in the lipid matrix. In vitro release was slow and sustained whereas ex vivo permeation parameters were significantly high in KTZ-SLNs as compared to free drug suspension (KTZ-SUS) and marketed product (Nizral®; 2% KTZ w/v). Drug retention was 10- and five-fold higher than KTZ-SUS and marketed product, respectively. In vivo dermatokinetics parameters improved significantly with SLN formulation (410-900% enhanced). Confocal Raman spectroscopy experiment showed that KTZ-SLNs could penetrate beyond the human stratum corneum into viable epidermis. Fluorescent microscopy also indicated improved penetration of KTZ-SLNs. KTZ-SLNs were photostable and showed long-term stability over 12 months under set conditions.

High yielding, one-step mechano-enzymatic hydrolysis of cellulose to cellulose nanocrystals without bulk solvent.

Traditional methods of enzymatic hydrolysis of cellulose to cellulose nanocrystals (CNCs) are limited due to the low enzymatic efficiency and large amount of waste liquid. The purpose of this study is to improve the yield and production efficiency of CNCs by enzymatic hydrolysis. A one-step mechano-enzymatic hydrolysis method was developed by utilizing the synergy of wet grinding and enzymatic hydrolysis reaction to efficiently prepare CNCs. Under the optimal reaction conditions, the maximum CNCs yield of 49.3% was achieved with higher thermal stability and crystallinity index of 76.7%. Mechano-enzymatic hydrolysis followed the first order pseudo-kinetics, and fractal kinetics demonstrated that mechanical force of rotation speed affected the fractal dimensions and binding ability between substrate and enzyme. This study provides an alternative method to prepare CNCs, which can significantly avoid the use of bulk water, improve the production efficiency of CNCs and thus lower the production cost.

Preparation of camptothecin micelles self-assembled from disodium glycyrrhizin and tannic acid with enhanced antitumor activity.

Natural compounds as carriers for hydrophobic drugs have been increasingly used in drug delivery systems. In this study, disodium glycyrrhizin (Na2GA), tannic acid (TA) and camptothecin (CPT) were firstly used to prepare the camptothecin solid dispersion (CPT SD). When dissolved in a solution medium, Na2GA self-assembled to form micelles and CPT was encapsulated in micelles, meanwhile, TA connected with Na2GA through hydrogen bonds to form a contract shell. The average diameter of the CPT-loaded micelles is 80 nm with the critical micellar concentration of 0.303 mg/mL, the zeta potential of -33 mV, the PDI of 0.25 and drug loading 6.22%. In vitro experiments confirmed that the drug-loaded micelles exhibited excellent stability and permeability in the intestinal environment. Furthermore, the formulation showed excellent anti-tumor activity in vitro and in vivo. These findings imply that this nano-micelles provide a more potential and efficacious oral drug formulation for chemotherapy.

Loss of the Tg737 protein results in skeletal patterning defects.

Tg737 mutant mice exhibit pathologic conditions in numerous tissues along with skeletal patterning defects. Herein, we characterize the skeletal pathologic conditions and confirm a role for Tg737 in skeletal patterning through transgenic rescue. Analyses were conducted in both the hypomorphic Tg737(orpk) allele that results in duplication of digit one and in the null Tg737(delta2-3betaGal) allele that is an embryonic lethal mutation exhibiting eight digits per limb. In early limb buds, Tg737 expression is detected throughout the mesenchyme becoming concentrated in precartilage condensations at later stages. In situ analyses indicate that the Tg737(orpk) mutant limb defects are not associated with changes in expression of Shh, Ihh, HoxD11-13, Patched, BMPs, or Glis. Likewise, in Tg737(delta2-3betaGal) mutant embryos, there was no change in Shh expression. However, in both alleles, Fgf4 was ectopically expressed on the anterior apical ectodermal ridge. Collectively, the data argue for a dosage effect of Tg737 on the limb phenotypes and that the polydactyly is independent of Shh misexpression.