Characterization, Molecular Docking, and In Vitro Dissolution Studies of Solid Dispersions of 20(S)-Protopanaxadiol.

In this study, we prepared solid dispersions (SDs) of 20(S)-protopanaxadiol (PPD) using a melting-solvent method with different polymers, in order to improve the solubility and dissolution performance of drugs with poor water solubility. The SDs were characterized via differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR), and molecular docking and dynamics study. DSC and PXRD results indicated that PPD crystallinity in SDs was significantly reduced, and that the majority of PPD is amorphous. No interaction was observed between PPD and polymers on FTIR and NMR spectra. Molecular docking and dynamic calculations indicated that the PPD molecule localized to the interpolated charged surface, rather than within the amorphous polymer chain network, which might help prevent PPD crystallization, consequently enhancing the PPD dispersion in polymers. An in vitro dissolution study revealed that the SDs considerably improved the PPD dissolution performance in distilled water containing 0.35% Tween-80 (T-80). Furthermore, among three PPD-SDs formulations, Poloxamer188 (F68) was the most effective in improving the PPD solubility and was even superior to the mixed polymers. Therefore, the SD prepared with F68 as a hydrophilic polymer carrier might be a promising strategy for improving solubility and in vitro dissolution performance. F68-based SD, containing PPD with a melting-solvent preparation method, can be used as a promising, nontoxic, quick-release, and effective intermediate for other pharmaceutical formulations, in order to achieve a more effective drug delivery.

Revised sample preparation for the analysis of oxysterols by enzyme-assisted derivatisation for sterol analysis (EADSA).

Sterols, and specifically oxysterols, play important roles in the biosynthesis of bile acids and steroid hormones as well as possessing biological activities in their own right. Analysis of oxysterols is complicated due to their low abundance in biological systems and poor ionisation characteristics in mass spectrometry. Over the past decade, we have developed a liquid chromatography-mass spectrometry method termed enzyme-assisted derivatisation for sterol analysis (EADSA). Our derivatisation procedure relies on two solid-phase extraction steps to (i) separate cholesterol from oxysterols and (ii) remove excess derivatisation reagents. Recent inter-batch variation in C18 reversed-phase cartridges has led us to experiment with alternative columns. Here, we present our findings and report an improved sample preparation procedure using polymeric hydrophilic-lipophilic balanced reversed-phase cartridges.

Multifunctional nanogel loaded with cerium oxide nanozyme and CX3CL1 protein: Targeted immunomodulation and retinal protection in uveitis rat model.

Effectively addressing retinal issues represents a pivotal aspect of blindness-related diseases. Novel approaches involving reducing inflammation and rebalancing the immune response are paramount in the treatment of these conditions. This study delves into the potential of a nanogel system comprising polyethylenimine-benzene boric acid-hyaluronic acid (PEI-PBA-HA). We have evaluated the collaborative impact of cerium oxide nanozyme and chemokine CX3CL1 protein for targeted immunomodulation and retinal protection in uveitis models. Our nanogel system specifically targets the posterior segment of the eyes. The synergistic effect in this area reduces oxidative stress and hampers the activation of microglia, thereby alleviating the pathological immune microenvironment. This multifaceted drug delivery system disrupts the cycle of oxidative stress, inflammation, and immune response, suppressing initial immune cells and limiting local retinal structural damage induced by excessive immune reactions. Our research sheds light on interactions within retinal target cells, providing a promising avenue for the development of efficient and innovative drug delivery platforms.

Transcriptomic and metabonomic insights into the biocontrol mechanism of Trichoderma asperellum M45a against watermelon Fusarium wilt.

Watermelon (Citrullus lanatus) is one of the most popular fruit crops. However, Fusarium wilt (FW) is a serious soil-borne disease caused by Fusarium oxysporum f. sp. niveum (FON) that severely limits the development of the watermelon industry. Trichoderma spp. is an important plant anti-pathogen biocontrol agent. The results of our previous study indicated that Trichoderma asperellum M45a (T. asperellum M45a) could control FW by enhancing the relative abundance of plant growth-promoting rhizobacteria (PGPR) in the rhizosphere of watermelon. However, there are few studies on its mechanism in the pathogen resistance of watermelon. Therefore, transcriptome sequencing of T. asperellum M45a-treated watermelon roots combined with metabolome sequencing of the rhizosphere soil was performed with greenhouse pot experiments. The results demonstrated that T. asperellum M45a could stably colonize roots and significantly increase the resistance-related enzymatic activities (e.g., lignin, cinnamic acid, peroxidase and peroxidase) of watermelon. Moreover, the expression of defense-related genes such as MYB and PAL in watermelon roots significantly improved with the inoculation of T. asperellum M45a. In addition, KEGG pathway analysis showed that a large number of differentially expressed genes were significantly enriched in phenylpropane metabolic pathways, which may be related to lignin and cinnamic acid synthesis, thus further inducing the immune response to resist FON. Furthermore, metabolic analysis indicated that four differential metabolic pathways were enriched in M45a-treated soil, including six upregulated compounds and one down-regulated compound. Among them, galactinol and urea were significantly positively correlated with Trichoderma. Hence, this study provides insight into the biocontrol mechanism of T. asperellum M45a to resist soil-borne diseases, which can guide its industrial application.

An injectable thermosensitive hydrogel for dual delivery of diclofenac and Avastin® to effectively suppress inflammatory corneal neovascularization.

Corneal neovascularization (CNV) is a sequela of anterior segment inflammation, which could lead to vision impairment and even blindness. In the present study, the dual delivery of anti-inflammatory agent (i.e., diclofenac; DIC) and anti-VEGF antibody (i.e., Avastin®; Ava) by the thermosensitive hydrogel (Poly(dl-lactide)-poly(ethylene glycol)-poly(dl-lactide); PDLLA-PEG-PDLLA) is expected to effectively inhibit CNV via their synergistic effects. The optimal DIC micelles were formulated and then mixed with Ava and PDLLA-PEG-PDLLA aqueous solution to generate various DIC@Ava-loaded hydrogels. The co-encapsulation of DIC micelles and Ava did not influence the gelling behavior of the system, and the resulting DIC@Ava-loaded hydrogel provided sustained drug release of both DIC and Ava without compromising their pharmacological activity over 19 days. As indicated by in vitro cytotoxicity and in vivo ocular biocompatibility test, the proposed PDLLA-PEG-PDLLA hydrogel caused minimal cytotoxicity against all tested cell lines at a polymeric concentration ranging from 0.05 mg/mL to 0.8 mg/mL and demonstrated good ocular biocompatibility after a single subconjunctival injection. Using the rabbit CNV model, we documented the superior anti-angiogenic effects of the DIC@Ava-loaded hydrogel over Ava alone medication (treatment with Ava solution and Ava-loaded hydrogel) due to synergistic effects of anti-VEGF and anti-inflammatory action. Overall, the proposed DIC@Ava-loaded hydrogel might be a powerful strategy to reduce CNV.

Single subcutaneous injection of the minocycline nanocomposite-loaded thermosensitive hydrogel for the effective attenuation of experimental autoimmune uveitis.

Autoimmune uveitis induces a serious pathological and inflammatory response in the retina/choroid and results in vision impairment and blindness. Here, we report a minocycline (Mino) nanocomposite-loaded hydrogel offering a high drug payload and sustained drug release for the effective control of ocular inflammation via a single subcutaneous injection. In the presence of divalent cations (i.e., Ca2+), Mino was found to co-assemble with a phosphorylated peptide (i.e., NapGFFpY) via electrostatic interaction and consequently generating Mino nanocomposite. The drug entrapment efficiency (EE) of the Mino nanocomposite varied from 29.93 ± 0.76% to 67.90 ± 6.57%, depending on different component concentrations. After incorporation into 30 wt% poly (D,L-lactide)-b-poly (ethylene glycol)-b-poly (D,L-lactide) (PDLLA-PEG-PDLLA) thermosensitive hydrogel, the resulting Mino nanocomposite-loaded hydrogel provided a sustained drug release over 21 days. In the experimental autoimmune uveitis (EAU) rat model, a single subcutaneous injection of the Mino nanocomposite-loaded hydrogel effectively alleviated ocular inflammation in a dose-dependent manner. As indicated by optical coherence tomography (OCT) and electroretinogram (ERG) measurements, the Mino nanocomposite-loaded hydrogel treatment not only remarkably reduced destruction of the retina by EAU, but also greatly rescued retinal functions. Moreover, the proposed Mino nanocomposite-loaded hydrogel exerted its therapeutic effect on EAU primarily through a significant reduction of the influx of leukocytes and Th17 cells as well as suppression of microglia activation and apoptosis in the retina. Overall, the proposed Mino nanocomposite-loaded hydrogel might be a promising strategy for the clinical management of EAU.

[Comparison of stability of acrylic intraocular lens and transparency of lens capsule using Pentacam Scheimpflug System].

OBJECTIVE: To compare the amounts of intraocular lens (IOL) decentration and tilt, the anterior chamber depth (ACD) and the degree of posterior capsule opacification (PCO) using the Pentacam Scheimpflug System after cataract surgery between eyes with 1-piece acrylic IOL and 3-piece acrylic IOL. METHODS: It was a perspective study. Fifty-one patients with bilateral senile cataract had implantation of a 1-piece SA60AT IOL in one eye and a 3-piece MA60BM IOL in the contralateral eye. The amount of IOL decentration, tilt, the ACD, and the degree of PCO was measured using the Pentacam Scheimpflug System 1 day and 1, 6, 12 and 24 months postoperatively. RESULTS: There were no significant changes during the 24 m follow-up period in the decentration (0.37 ± 0.16, 0.36 ± 0.15, 0.36 ± 0.16, 0.37 ± 0.15, 0.38 ± 0.16), tilt (3.59 ± 0.91, 3.64 ± 0.92, 3.61 ± 0.90, 3.63 ± 0.90, 3.70 ± 0.89) or PCO (22.20 ± 3.99, 21.96 ± 4.00, 22.40 ± 4.03, 22.53 ± 4.00, 22.95 ± 3.87) in the 1-piece SA60AT group (F = 1.938, 0.785, 1.814; P > 0.05) or in the 3-piece MA60BM group (0.34 ± 0.14, 0.33 ± 0.14, 0.34 ± 0.14, 0.35 ± 0.14, 0.36 ± 0.14), (3.55 ± 0.90, 3.57 ± 0.92, 3.63 ± 0.88, 3.61 ± 0.88, 3.65 ± 0.89), (21.14 ± 3.88, 20.98 ± 3.87, 21.23 ± 3.83, 21.59 ± 3.82, 21.65 ± 3.87) (F = 1.004, 0.525, 1.963; P > 0.05). There was no significant difference between the two groups in IOL decentration (t = 0.802, 0.701, 0.588, 0.898, 0.631), tilt (t = 0.199, 0.337, 0.094, 0.121, 0.248) or PCO (t = 1.214, 1.119, 1.334, 1.082, 1.517) at any time points (P > 0.05). The ACD did not change after the surgery in the 1-piece group (3.90 ± 0.99, 3.88 ± 1.07, 3.91 ± 1.01, 3.90 ± 1.02, 3.92 ± 1.02) (F = 1.333, P > 0.05) but was significantly deeper in the 3-piece group (4.37 ± 1.02, 3.90 ± 0.98, 3.95 ± 0.99, 3.93 ± 0.96, 3.97 ± 0.99) (F = 92.757, P < 0.05) one day after the operation. The ACD was more shallow in the 1-piece SA60AT group than in the 3-piece MA60BM group at all time points. However, the difference was statistically significant only at 1 day after surgery (t = 102.944, P < 0.05). CONCLUSIONS: The degrees of IOL decentration, tilt, ACD and PCO in eyes with a 1-piece acrylic IOL with flexible haptics implanted in the capsular bag were similar to those in eyes with a 3-piece acrylic IOL with rigid PMMA haptics. But the 1-piece acrylic IOL provides a better stability than the 3-piece acrylic IOL in the early stage postoperatively.