Colon-targeted hydroxyethyl starch-curcumin microspheres with high loading capacity ameliorate ulcerative colitis via alleviating oxidative stress, regulating inflammation, and modulating gut microbiota.

Curcumin (CUR) is a natural polyphenol that holds promise for treating ulcerative colitis (UC), yet oral administration of CUR exhibits limited bioavailability and existing formulations for oral delivery of CUR often suffer from unsatisfactory loading capacity. This study presents hydroxyethyl starch-curcumin microspheres (HC-MSs) with excellent CUR loading capacity (54.52 %), and the HC-MSs can further encapsulate anti-inflammatory drugs dexamethasone (DEX) to obtain a combination formulation (DHC-MSs) with high DEX loading capacity (19.91 %), for combination therapy of UC. The microspheres were successfully engineered, retaining the anti-oxidative and anti-inflammatory activities of parental CUR and demonstrating excellent biocompatibility and controlled release properties, notably triggered by α-amylase, facilitating targeted drug delivery to inflamed sites. In a mouse UC model induced by dextran sulfate sodium, the microspheres effectively accumulated in inflamed colons and both HC-MSs and DHC-MSs exhibited superior therapeutic efficacy in alleviating UC symptoms compared to free DEX. Moreover, mechanistic exploration uncovered the multifaceted therapeutic mechanisms of these formulations, encompassing anti-inflammatory actions, mitigation of spleen enlargement, and modulation of gut microbiota composition. These findings underscore the potential of HC-MSs and DHC-MSs as promising formulations for UC, with implications for advancing treatment modalities for various inflammatory bowel disorders.

Colon-Targeted Oral Delivery of Hydroxyethyl Starch-Curcumin Microcapsules Loaded with Multiple Drugs Alleviates DSS-Induced Ulcerative Colitis in Mice.

Combination therapy through colon-targeted oral delivery of multiple drugs presents a promising approach for effectively treating ulcerative colitis (UC). However, the codelivery of drugs with diverse physicochemical properties in a single formulation remains a formidable challenge. Here, microcapsules are designed based on hydroxyethyl starch-curcumin (HES─CUR) conjugates to enable the simultaneous delivery of hydrophobic dexamethasone acetate (DA) and hydrophilic cefazolin sodium (CS), yielding multiple drug-loaded microcapsules (CS/DA-loaded HES─CUR microcapsules, CDHC-MCs) tailored for colon-targeted therapy of UC. Thorough characterization confirms the successful synthesis and exceptional biocompatibility of CDHC-MCs. Biodistribution studies demonstrate that the microcapsules exhibit an impressive inflammatory targeting effect, accumulating preferentially in inflamed colons. In vivo experiments employing a dextran-sulfate-sodium-induced UC mouse model reveal that CDHC-MCs not only arrest UC progression but also facilitate the restoration of colon length and alleviate inflammation-related splenomegaly. These findings highlight the potential of colon-targeted delivery of multiple drugs within a single formulation as a promising strategy to enhance UC treatment, and the CDHC-MCs developed in this study hold great potential in developing novel oral formulations for advanced UC therapy.

Improvement of mild photoaged facial skin in middle-aged Chinese females by a supramolecular retinol plus acetyl hexapeptide-1 containing essence.

Background: The anti-ageing gold standard, retinol, has been widely recognized for its anti-wrinkle benefits in the Chinese population. Studies have shown that Asians are more sensitive to retinol compared to their Caucasian counterparts, and it is generally recommended to use retinol once a day in the evening. However, there are few reports on the most appropriate concentration and frequency of retinol use in the general Chinese population. Objectives: In this study, supramolecular retinol was prepared using cyclodextrin encapsulation technology, and the most appropriate concentration for the general Chinese population was investigated. Then, a cosmetic essence was developed by combining the classic supramolecular retinol, which promotes collagen regeneration, with acetyl hexapeptide-1, a popular ingredient known for reducing expression lines. The safety and efficacy of this cosmetic essence were studied through clinical tests. Methods: First, a patch test was conducted on 32 healthy Chinese subjects to compare the tolerance of supramolecular retinol to non-encapsulated retinol and to select the optimal concentration of retinol. Then, an 8-week clinical study was conducted using a twice-daily cosmetic essence containing 0.1% supramolecular retinol and 0.02% acetyl hexapeptide-1 to treat mild photoaging in 32 middle-aged Chinese women. Dermatological evaluations and instrument measurements were taken at baseline, 4 weeks, and 8 weeks. Efficacy was assessed using facial skin wrinkles, textures, elasticity, firmness, pores, gloss and stratum corneum hydration. Tolerability was assessed throughout the study. Results: Our patch test results showed that supramolecular retinol was better tolerated than non-encapsulated retinol, and our findings suggest that 0.1% was the approximate optimal retinol concentration for the general Chinese population. The cosmetic essence studied was effective in improving the appearance of photoaged skin in the Chinese population in all aspects studied and was well tolerated. Conclusions: 0.1% retinol is suitable for twice daily use in the general Chinese population. Data and records on efficacy dimensions of skin textures, elasticity, firmness, pores, gloss and stratum corneum hydration for retinol in the Chinese population are supplemented with our study. Cosmeceutical approaches targeting both static and dynamic wrinkles are of value for treating the photoaged Chinese population.

Colon-targeted oral nanoparticles based on ROS-scavenging hydroxyethyl starch-curcumin conjugates for efficient inflammatory bowel disease therapy.

Co-delivery of anti-inflammatory drugs and reactive oxygen species (ROS) scavengers by stimuli-responsive oral nanoparticles is deemed to be a favorable strategy for inflammatory bowel disease (IBD) therapy. In this study, using micelles formed by CUR conjugated hydroxyethyl starch (HES) as vehicles, dexamethasone (DEX)-loaded HES-CUR nanoparticles (DHC NPs) with desirable size, negative surface charge, good stability in the harsh gastric environment, and excellent ROS scavenging activity are developed as a colon-targeted oral formulation for treating IBD. Due to the degradation of HES in response to α-amylase overexpressed in the inflamed colon, the DHC NPs release drugs in an α-amylase-responsive manner. Meanwhile, the DHC NPs can be effectively internalized by macrophages and show excellent cytocompatibility with macrophages since they are composed of food-derived compounds. Importantly, in vivo studies reveal that the DHC NPs are capable of targeting the inflamed colon induced by dextran sulfate sodium (DSS), and the targeted and combination therapy enhances the efficacy of free DEX and significantly relieves the impairment caused by DSS-induced ulcerative colitis. Incorporating the merits of targeted drug delivery and combined therapy with an anti-inflammatory drug and ROS scavenger, the DHC NPs are promising for developing novel oral formulations for IBD therapy.

Removal of harmful algae by Shigella sp. H3 and Alcaligenes sp. H5: algicidal pathways and characteristics.

Application of algicidal bacteria is a promising technology to control harmful algal blooms (HABs). In this study, algicidal bacteria strains Shigella sp. H3 and Alcaligenes sp. H5 were obtained via two different isolation methods from the same lake water sample, with optimal algicidal efficiencies 96% and 74% against algae mixture. The Shigella sp. H3 and Alcaligenes sp. H5 lysed algae cells through cells-to-cells direct contact and secretion of algicidal metabolites, respectively. The stronger algicidal capability of Shigella sp. H3 was also attributable to its higher efficiency for triggering reactive oxygen species, which led to broken down of the antioxidant system and more severe damage to the bacterial cells. The antioxidant enzyme activities in Alcaligenes sp. H5 group were still expressed because of its relatively weaker algicidal capability and some intact algal cells were remained. The liquid carbohydrates from algal lysis in both groups increased significantly, whereas the quantities of liquid protein decreased, which might be assimilated by algicidal bacteria. Nonetheless, the whole algicidal process resulted in the increase of total released organic matters content. This study revealed the algicidal pathways of diverse bacterial strains, and the possible secondary environmental problem caused by the algal released organic matters should be considered when applying bacteria to control HABs.

Aldehyde dehydrogenase 2 deficiency significantly exacerbates tert-butyl alcohol-induced toxicity in mice.

Owing to the use of ethyl tert-butyl ether (ETBE) as a fuel additive, the possible adverse effects of ETBE exposure have become a public concern. Our previous study showed that ETBE-induced toxicity in aldehyde dehydrogenase 2 (Aldh2) gene knockout (KO) mice was caused by its primary metabolite acetaldehyde, which was toxic. However, it is unclear whether tert-butyl alcohol (TBA), another main metabolite of ETBE, plays a role in ETBE-induced toxicity. To investigate this relationship, we analyzed the changes of TBA concentrations in tissues after ETBE exposure, and then evaluated the toxicity after direct TBA treatment in both KO and wild-type (WT) mice. An exposure to 500 ppm ETBE via inhalation resulted in the formation of its three metabolites, TBA, 2-methyl-1,2-propanediol and ethanol, whose concentrations in the liver, brain, fat and testis of male KO mice were significantly higher than the corresponding concentrations observed in male WT mice. Direct treatment to TBA (20 mg/mL of drinking water) caused significant changes in relative organ weights and histopathology, and increased levels of genetic damages in both types of mice. These toxic effects were also seen in KO mice exposed to a lower concentration of TBA (5 mg/mL), which was associated with increased oxidative stress in serum (reduced glutathione and reduced glutathione/oxidized glutathione ratio decreased). Our findings indicate that ALDH2 is involved in the metabolism of ETBE and TBA, and ALDH2 deficiency could greatly increase the sensitivity to TBA-induced toxicity.

Nano-micelles based on hydroxyethyl starch-curcumin conjugates for improved stability, antioxidant and anticancer activity of curcumin.

In this study, amphiphilic conjugates were synthesized by conjugating curcumin (CUR) to a food-derived hydrophilic hydroxyethyl starch (HES) via an acid-labile ester linker. The self-assembly of the conjugates formed uniform micellar nanoparticles (HES-CUR NPs) with a desirable drug loading efficiency, excellent colloidal and storage stability, as well as acid-responsive release manner. Besides, the formation of the nanoparticles increased the solubility of CUR to thousands times higher than free CUR, and effectively protected the loaded CUR from degradation upon exposure to UV light and high temperature. In vitro cytotoxicity assay and radical scavenging experiments demonstrated that the HES-CUR NPs significantly improved the cytocompatibility, anticancer and antioxidant activity of CUR due to the enhanced solubility, stability, and bioavailability. The HES-CUR NPs reported herein have a great potential in developing functional food or pharmaceutical formulations for preventing or treating various diseases such as inflammatory diseases and cancer.