Weaverbehrens8577

The curcumin-loaded nanoparticle/hydrogel composite was able to sustain release payload for up to four weeks. The optimized nanoparticle/hydrogel composite showed effective inhibition of human UM cell proliferation. This novel nanoparticle/in situ hydrogel composite demonstrated a great potential for the treatment of the rare and devastating intraocular cancer.Treatment of invasive infections caused by Candida auris is challenging due to the limited therapeutic options. The combination of antifungal drugs may be an interesting and feasible approach to be investigated. The aim of this study was to examine the in vitro activity of amphotericin B in combination with anidulafungin or caspofungin against C. auris. In vitro static time-kill curve experiments were conducted for 48 h with different combinations of amphotericin B with anidulafungin or caspofungin against six blood isolates of C. auris. The antifungal activity of 0.5 mg/L of amphotericin B was limited against the six isolates of C. auris. Similarly, echinocandins alone had a negligible effect, even at the highest tested concentrations. By contrast, 1 mg/L of amphotericin B showed fungistatic activity. Synergy was rapidly achieved (8 h) with 0.5 mg/L of amphotericin B plus 2 mg/L of anidulafungin or caspofungin. These combinations lead to a sustained fungistatic effect, and the fungicidal endpoint was reached against some C. auris isolates. Additionally, ≥0.5 mg/L of either of the two echinocandins with 1 mg/L of amphotericin B resulted in fungicidal effect against all C. auris isolates. In conclusion, combinations of amphotericin B with anidulafungin or caspofungin provided greater killing with a lower dose requirement for amphotericin B compared to monotherapy, with synergistic and/or fungicidal outcomes.Photodynamic therapy (PDT) is a minimally invasive therapeutic modality that has gained great attention in the past years as a new therapy for cancer treatment. PDT uses photosensitizers that, after being excited by light at a specific wavelength, react with the molecular oxygen to create reactive oxygen species in the target tissue, resulting in cell death. Compared to conventional therapeutic modalities, PDT presents greater selectivity against tumor cells, due to the use of photosensitizers that are preferably localized in tumor lesions, and the precise light irradiation of these lesions. This paper presents a review of the principles, mechanisms, photosensitizers, and current applications of PDT. Moreover, the future path on the research of new photosensitizers with enhanced tumor selectivity, featuring the improvement of PDT effectiveness, has also been addressed. Finally, new applications of PDT have been covered.The anti-inflammatory, antifibrotic and antimicrobial activities of curcumin (CUR) are missed because of its low solubility in aqueous media, low bioavailability, and structural lability upon oral intake. Soft nanoparticles such as nanoliposomes are not efficient as CUR carriers, since crystalline CUR is expelled from them to physiological media. Nanostructures to efficiently trap and increase the aqueous solubility of CUR are needed to improve both oral or nebulized delivery of CUR. Here we showed that SRA1 targeted nanoarchaeosomes (nATC) [10.4 ww0.04] archaeolipids, tween 80 and CUR, 155 ± 16 nm sized of -20.7 ± 3.3 z potential, retained 0.22 mg CUR ± 0.09 per 12.9 mg lipids ± 4.0 (~600 μM CUR) in front to dilution, storage, and nebulization. Raman and fluorescence spectra and SAXS patterns were compatible with a mixture of enol and keto CUR tautomers trapped within the depths of nATC bilayer. Between 20 and 5 µg CUR/mL, nATC was endocytosed by THP1 and A549 liquid-liquid monolayers without noticeable cytotoxicity. Five micrograms of CUR/mL nATC nebulized on an inflamed air-liquid interface of A549 cells increased TEER, normalized the permeation of LY, and decreased il6, tnfα, and il8 levels. Overall, these results suggest the modified pharmacodynamics of CUR in nATC is useful for epithelia repair upon inflammatory damage, deserving further deeper exploration, particularly related to its targeting ability.Lyophilization is often employed to transform nanoparticle suspensions to stable solid forms. This work proposed Neurofuzzy Logic (NFL) to better understand the lyophilization process of Nanostructured Lipid Carriers' (NLCs) dispersions and the carbohydrate cryoprotectants' (CPs) performance in these processes. NLCs were produced by hot homogenization, frozen at different speeds, and lyophilized using several CPs at variable concentrations. NLCs were characterized, and results were expressed as increase in particle size (Δ size), polydispersity (Δ PdI), and zeta potential (Δ ZP) of lyophilized powders (LP) regarding initial dispersions. CPs were classified according to their molecular weights (MW), and the osmolarities (Π) of CPs solutions were also determined. Databases obtained were finally modelled through FormRules® (Intelligensys Ltd., Kirkwall, Scotland, UK), an NFL software. NFL models revealed that CPs' MW determines the optimal freezing conditions and CPs' proportions. The knowledge generated allowed the establishment of a traffic light system intended to successfully select and apply sugars for nanoparticles lyophilization.Transepidermal drug delivery achieves high drug concentrations at the action site and ensures continuous drug delivery and better patient compliance with fewer adverse effects. However, drug delivery through topical application is still limited in terms of drug penetration. Chitosan is a promising enhancer to overcome this constraint, as it can enhance drug diffusion by opening the tight junctions of the stratum corneum. Therefore, here, we developed a novel chitosan nanosponge (CNS) with an optimal ratio and molecular weight of chitosan to improve drug penetration through skin. To prepare the CNS, two types of chitosan (3 and 10 kDa) were each conjugated with poloxamer 407 using para-nitrophenyl chloroformate, and the products were mixed with poloxamer 407 at ratios of 55, 82, and 100. The resulting mixtures were molded to produce flexible soft nanosponges by simple nanoprecipitation. The CNSs were highly stable in biological buffer for four weeks and showed no toxicity in human dermal fibroblasts. The CNSs increased drug permeability through human cadaver skin in a Franz-type diffusion cell, with substantially higher permeability with 3 kDa chitosan at a ratio of 82. This suggests the applicability of the novel CNS as a promising carrier for efficient transepidermal drug delivery.Taxifolin, also known as dihydroquercetin, possesses several interesting biological properties. The purpose of the study was to identify polymorphs of taxifolin prepared using crystallization in different solvents. Data from X-ray powder diffraction, differential scanning calorimetry, and thermogravimetry enabled us to detect six different crystalline phases for taxifolin. Besides the already known fully hydrated phase, one partially hydrated phase, one monohydrated phase, two anhydrous polymorphs, and one probably solvated phase were obtained. The unit cell parameters were defined for three of them, while one anhydrous polymorph was fully structurally characterized by X-ray powder diffraction data. Scanning electron microscopy and hot stage microscopy were also employed to characterize the crystallized taxifolin powders. The hydrate and anhydrous forms showed remarkable stability in drastic storage conditions, and their solubility was deeply evaluated. The anhydrous form converted into the hydrate form during the equilibrium solubility study and taxifolin equilibrium solubility was about 1.2 mg/mL. The hydrate taxifolin intrinsic dissolution rate was 56.4 μg cm-2 min-1. Using Wood's apparatus, it was not possible to determine the intrinsic dissolution rate of anhydrous taxifolin that is expected to solubilize more rapidly than the hydrate form. In view of its high stability, its use can be hypothesized.Gastric cancer (GC) is a fatal malignant tumor, and effective therapies to attenuate its progression are lacking. Nanoparticle (NP)-based solutions may enable the design of novel treatments to eliminate GC. Refined, receptor-targetable NPs can selectively target cancer cells and improve the cellular uptake of drugs. To overcome the current limitations and enhance the therapeutic effects, epigallocatechin-3-gallate (EGCG) and low-concentration doxorubicin (DX) were encapsulated in fucoidan and d-alpha-tocopherylpoly (ethylene glycol) succinate-conjugated hyaluronic acid-based NPs for targeting P-selectin-and cluster of differentiation (CD)44-expressing gastric tumors. The EGCG/DX-loaded NPs bound to GC cells and released bioactive combination drugs, demonstrating better anti-cancer effects than the EGCG/DX combination solution. In vivo assays in an orthotopic gastric tumor mouse model showed that the EGCG/DX-loaded NPs significantly increased the activity of gastric tumors without inducing organ injury. Overall, our EGCG/DX-NP system exerted a beneficial effect on GC treatment and may facilitate the development of nanomedicine-based combination chemotherapy against GC in the future.Substance P (SP) is a small peptide commonly known as a preferential endogenous ligand for the transmembrane neurokinin-1 receptor. Nuclear Medicine procedures currently involve radiolabeled SP derivatives in peptide radioligand endotherapy of inoperable glioblastoma. Promising clinical results sparked the demand for facile production strategies for a functionalized 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-[Thi8, Met(O2)11]-SP to allow for rapid Gallium-68 or Bismuth-213 complexation. Therefore, we provide a simple kit-like radiotracer preparation method that caters for the gallium-68 activity eluted from a SnO2 generator matrix as well as preliminary results on the adaptability to produce [213Bi]Bi-DOTA-[Thi8, Met(O2)11]SP from the same vials containing the same starting material. Following a phase of radioanalysis for complexation of gallium-68 to DOTA-[Thi8, Met(O2)11]SP and assessing the radiolabeling parameters, the vials containing appropriate kit-prototype material were produced in freeministration. This investigation proposes a simple kit-like formulation of DOTA-[Thi8, Met(O2)11]SP-a first-line investigation into a user friendly, straightforward tracer preparation that would warrant efficient clinical investigations in the future. Quantitative radiolabeling was accomplished for [68Ga]Ga-DOTA-[Thi8, Met(O2)11]SP and [213Bi]Bi-DOTA-[Thi8, Met(O2)11]SP preparations; a key requirement when addressing the specific route of catheter-assisted co-injection directly into the intratumoral cavities.Uridine 5'-diphospho-glucuronosyltransferases (UGTs) are expressed in the small intestines, but prediction of first-pass extraction from the related metabolism is not well studied. This work assesses physiologically based pharmacokinetic (PBPK) modeling as a tool for predicting intestinal metabolism due to UGTs in the human gastrointestinal tract. Available data for intestinal UGT expression levels and in vitro approaches that can be used to predict intestinal metabolism of UGT substrates are reviewed. Human PBPK models for UGT substrates with varying extents of UGT-mediated intestinal metabolism (lorazepam, oxazepam, naloxone, zidovudine, cabotegravir, raltegravir, and dolutegravir) have demonstrated utility for predicting the extent of intestinal metabolism. Drug-drug interactions (DDIs) of UGT1A1 substrates dolutegravir and raltegravir with UGT1A1 inhibitor atazanavir have been simulated, and the role of intestinal metabolism in these clinical DDIs examined. Utility of an in silico tool for predicting substrate specificity for UGTs is discussed.