Homoatomic Polychalcogenide Nonlinear Optical Anionic Groups with Ultra-Large Optical Anisotropy.

Functional assembly of nonlinear optical (NLO) motifs with a large optical anisotropy is vital to the development of advanced NLO and birefringent materials. In this work, we highlight that, in addition to heteroatomic NLO motifs, homoatomic anionic clusters formed by aggregated anions (S, Se, Te) exhibit diverse chain-, ring-, and cage-like chemical structures as well as one-, two-, and three-dimensional motif alignments. The rich structural chemistry enables homoatomic polychalcogenides (HAPCs) to exhibit asymmetric structural features and anisotropic optical properties, with great potential for NLO and birefringent performance. Focusing on totally 55 binary HAPCs A2Qn (n = 2, 3, 4, 5; A = Na, K, Rb, Cs; Q = S, Se, Te) and their ternary analogues, we employ the state-of-the-art first-principles approach to systematically investigate the modulation evolution of their NLO and birefringent properties. Remarkably, Rb2Te3 and Na2TeSe2 exhibit rarely colossal birefringence (>1.0@10 µm) and NLO effects (>20 × AgGaS2), much larger than conventional NLO chalcogenides. Na2Te3 presents the largest birefringence to date (∼3.48@1, 2.72@2, 2.34@10 µm), indicating the unique structural superiority of HAPC in terms of ultra-large birefringence. By mining the intrinsic mechanism, the HAPC anionic groups are identified as novel mid-infrared NLO "material genes", furnishing unique NLO and birefringent performance for the design of novel optoelectronic materials.

Pre-coating cRGD-modified bovine serum albumin enhanced the anti-tumor angiogenesis of siVEGF-loaded chitosan-based nanoparticles by manipulating the protein corona composition.

Chitosan-based nanoparticles inevitably adsorb numerous proteins in the bloodstream, forming a protein corona that significantly influences their functionality. This study employed a pre-coated protein corona using cyclic Arg-Gly-Asp peptide (cRGD)-modified bovine serum albumin (BcR) to confer tumor-targeting capabilities on siVEGF-loaded chitosan-based nanoparticles (CsR/siVEGF NPs) and actively manipulated the serum protein corona composition to enhance their anti-tumor angiogenesis. Consequently, BcR effectively binds to the nanoparticles' surface, generating nanocarriers of appropriate size and stability that enhance the inhibition of endothelial cell proliferation, migration, invasion, and tube formation, as well as suppress tumor proliferation and angiogenesis in tumor-bearing nude mice. Proteomic analysis indicated a significant enrichment of serotransferrin, albumin, and proteasome subunit alpha type-1 in the protein corona of BcR-precoated NPs formed in the serum of tumor-bearing nude mice. Additionally, there was a decrease in proteins associated with complement activation, immunoglobulins, blood coagulation, and acute-phase responses. This modification resulted in an enhanced impact on anti-tumor angiogenesis, along with a reduction in opsonization and inflammatory responses. Therefore, pre-coating of nanoparticles with a functionalized albumin corona to manipulate the composition of serum protein corona emerges as an innovative approach to improve the delivery effectiveness of chitosan-based carriers for siVEGF, targeting the inhibition of tumor angiogenesis.

Silk Fibroin Formed Bioadhesive Ophthalmic Gel for Dry Eye Syndrome Treatment.

PURPOSE: Dry eye syndrome (DES), arising from various etiologic factors, leads to tear film instability and ocular surface damage. Given its anti-inflammatory effects, cyclosporine A (CsA) has been widely used as a short-term treatment option for DES. However, poor bioavailability and solubility of CsA in aqueous phase make the development of a cyclosporine A-based eye drop for ocular topical application a huge challenge. METHODS: In this study, a novel strategy for preparing cyclosporine A-loaded silk fibroin nanoemulsion gel (CsA NBGs) was proposed to address these barriers. Additionally, the rheological properties, ocular irritation potential, tear elimination kinetics, and pharmacodynamics based on a rabbit dry eye model were investigated for the prepared CsA NBGs. Furthermore, the transcorneal mechanism across the ocular barrier was also investigated. RESULTS: The pharmacodynamics and pharmacokinetics of CsA NBGs exhibited superior performance compared to cyclosporine eye drops, leading to a significant enhancement in the bioavailability of CsA NBGs. Furthermore, our investigation into the transcorneal mechanism of CsA NBGs revealed their ability to be absorbed by corneal epithelial cells via the paracellular pathway. CONCLUSION: The CsA NBG formulation exhibits promising potential for intraocular drug delivery, enabling safe, effective, and controlled administration of hydrophobic drugs into the eye. Moreover, it enhances drug retention within the ocular tissues and improves systemic bioavailability, thereby demonstrating significant clinical translational prospects.

Synthesis, Structure, and Optical Properties of a 0D Hybrid Organic-Inorganic Metal Halide (C5N2H14Cl)GeCl3.

Due to the flexible structural tunability and excellent photoelectric performance, hybrid organic-inorganic metal halides (OIMHs) have attracted intensive attention and become a hot topic in the field of materials. It is important and necessary to explore new OIMHs and study their structure-property relationship. In this work, a new lead-free OIMH, (C5N2H14Cl)GeCl3, is synthesized by the combination of hydrothermal and solution methods. This compound features a zero-dimensional structure composed of inorganic [GeCl3]- trigonal pyramids surrounded by isolated Cl- anions and organic (C5N2H14)2+ cations. Preliminary characterization and first-principles calculations are performed to study its basic optical properties. Interestingly, (C5N2H14Cl)GeCl3 shows weak blue emission under ultraviolet excitation, and the intrinsic mechanism is discussed.

Realizing Persistent Zero Area Compressibility over a Wide Pressure Range in Cu2 GeO4 by Microscopic Orthogonal-Braiding Strategy.

Zero area compressibility (ZAC) is an extremely rare mechanical response that exhibits an invariant two-dimensional size under hydrostatic pressure. All known ZAC materials are constructed from units in two dimensions as a whole. Here, we propose another strategy to obtain the ZAC by microscopically orthogonal-braiding one-dimensional zero compressibility strips. Accordingly, ZAC is identified in a copper-based compound with a planar [CuO4 ] unit, Cu2 GeO4 , that possesses an area compressibility as low as 1.58(26) TPa-1 over a wide pressure range from ≈0 GPa to 21.22 GPa. Based on our structural analysis, the subtle counterbalance between the shrinkage of [CuO4 ] and the expansion effect from the increase in the [CuO4 ]-[CuO4 ] dihedral angle attributes to the ZAC response. High-pressure Raman spectroscopy, in combination with first-principles calculations, shows that the electron transfer from in-plane bonding dx 2 -y 2 to out-of-plane nonbonding dz 2 orbitals within copper atoms causes the counterintuitive extension of the [CuO4 ]-[CuO4 ] dihedral angle under pressure. Our study provides an understanding on the pressure-induced structural evolution of copper-based oxides at an electronic level and facilitates a new avenue for the exploration of high-dimensional anomalous mechanical materials.

RNA extraction-free workflow integrated with a single-tube CRISPR-Cas-based colorimetric assay for rapid SARS-CoV-2 detection in different environmental matrices.

On-site environmental surveillance of viruses is increasingly important for infection prevention and pandemic control. Herein, we report a facile single-tube colorimetric assay for detecting severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) from environmental compartments. Using glycerol as the phase separation additive, reverse transcription recombinase polymerase amplification (RT-RPA), CRISPR-Cas system activation, G-quadruplex (G4) cleavage, and G4-based colorimetric reaction were performed in a single tube. To further simplify the test, viral RNA genomes used for the one-tube assay were obtained via acid/base treatment without further purification. The whole assay from sampling to visual readout was completed within 30 min at a constant temperature without the need for sophisticated instruments. Coupling the RT-RPA to CRISPR-Cas improved the reliability by avoiding false positive results. Non-labeled cost-effective G4-based colorimetric systems are highly sensitive to CRISPR-Cas cleavage events, and the proposed assay reached the limit of detection of 0.84 copies/µL. Moreover, environmental samples from contaminated surfaces and wastewater were analyzed using this facile colorimetric assay. Given its simplicity, sensitivity, specificity, and cost-effectiveness, our proposed colorimetric assay is highly promising for applications in on-site environmental surveillance of viruses.

Analysis of degradation kinetic modeling and mechanism of chlorinated-halonitromethanes under UV/monochloramine treatment.

Chlorinated-halonitromethanes (Cl-HNMs) including chloronitromethane (CNM), dichloronitromethane (DCNM), and trichloronitromethane (TCNM) are nitrogenous disinfection by-products, which have high cytotoxicity and genotoxicity to human. This study aimed to investigate the degradation kinetic modeling and mechanism of Cl-HNMs under monochloramine activated by ultraviolet of 254 nm (UV/NH2Cl) treatment. The first-principle kinetic model of UV/NH2Cl process was developed to simulate Cl-HNMs degradation. Of note, the second-order rate constants of Cl-HNMs reacting with HO• (∼108 M-1 s-1), Cl• (kCl•,CNM or DCNM = âˆ¼1010 M-1 s-1, kCl•,TCNM = âˆ¼102 M-1 s-1), Cl2•- (kCl•,CNM or DCNM = âˆ¼109 M-1 s-1, kCl•,TCNM = âˆ¼101 M-1 s-1), ClO• (∼105-106 M-1 s-1) and CO3•- (∼106-107 M-1 s-1) were obtained by the first-principle kinetic model. Overall, Cl-HNMs degradation under UV/NH2Cl treatment was successfully predicted by the kinetic model under various conditions. It was found that UV (>60%) was dominant in Cl-HNMs degradation, followed by HO• (3.8%-24.5%), reactive chlorine species (RCS, 0.9%-28.8%) and CO3•- (0-26.1%). Among the contributions of RCS, Cl• and Cl2•- were main radicals in the degradation of CNM and DCNM, while ClO• was responsible for the abatement of TCNM. The minimum EE/O values under UV/NH2Cl treatment were approximately 30% lower than those under UV treatment. Finally, the possible degradation pathways were proposed, including hemolytic/heterolytic cleavage of Cl-HNMs by UV irradiation, hydrogen abstraction/electron transfer of CNM and DCNM and adduct reaction of TCNM by free radicals. This study based on the kinetic model is beneficial to predict and control the concentrations of Cl-HNMs under UV/NH2Cl treatment.

Bolus delivery of palonosetron through skin by tip-loaded dissolving microneedles with short-duration iontophoresis: A potential strategy to rapidly relieve emesis associated with chemotherapy.

The objective of this study was to investigate the feasibility of the bolus administration of PLS via skin by using dissolving microneedles of palonosetron hydrochloride (PLS-DMNs). Tip-loaded PLS-DMNs were fabricated by a casting method using sodium hyaluronate (HA) as DMNs-forming polymer. PLS-DMNs were shown to have a content of 118.5 ± 8.7 µg per piece with sufficient mechanical strength for insertion into pig skin ex vivo. In situ dissolution of PLS-DMNs was achieved within 5 min and 83.2 % of PLS was delivered. In vitro studies showed that PLS-DMNs provided much higher PLS permeation than that after passive permeation using a PLS hydrogel. Moreover, the application of 30 min-iontophoresis at the beginning of PLS-DMNs administration further enhanced PLS delivery. In vivo pharmacokinetic studies were carried out in rats. The area under the curve (AUC) and the time to reach the peak (Tmax) after application of PLS-DMNs was not significantly different compared to those after subcutaneous (S.C.) injection. PLS-DMNs plus 30 min-iontophoresis enabled the pharmacokinetic profile to be even closer to that seen after S.C. administration. These results suggest that application of PLS-DMNs with short-duration iontophoresis exhibits promise as an alternative PLS delivery method that can be painlessly self-administered with rapid onset.

[Degradation of Chloroquine Phosphate by UV-activated Persulfate].

The degradation of chloroquine phosphate (CQP), an anti-COVID-19 drug, was investigated in a UV-activated persulfate system (UV/PS). The second-order rate constants of CQP with hydroxyl radicals (HO·) and sulfate radicals (SO4-·) were determined using a competition kinetics experiment, and the effects of persulfate concentration, pH, and inorganic anions on the degradation of CQP were also systematically studied. Furthermore, a kinetic model was established to predict the concentration of CQP and major free radicals to explore its mechanism of influence. The results showed that the degradation efficiency of CQP could reach 91.3% after 10 min under UV/PS, which was significantly higher than that under UV, sunlight, or PS alone. At pH=6.9, the second-order rate reaction constants of CQP with HO· and SO4-· were 8.9×109 L·(mol·s)-1and 1.4×1010 L·(mol·s)-1, respectively, and the main active species was SO4-·. The degradation rate of CQP increased with increasing concentrations of PS and decreased with the addition of HCO3- and Cl-. The removal efficiency of CQP was inhibited under stronger alkaline conditions. N-de-ethylation, cleavage of the C-N bond, and hydrogen abstraction were proposed as the principal pathways of CQP degradation based on LC-MS analysis. The mineralization rate of CQP could be improved by increasing PS concentration and pH values. This study could be helpful for the treatment of anti-COVID-19 pharmaceutical wastewater.

Fast In Vitro Release and In Vivo Absorption of an Anti-Schizophrenic Drug Paliperidone from Its Soluplus®/TPGS Mixed Micelles.

The purpose of this study was to develop a drug delivery system for paliperidone (PPD) in order to provide a more effective therapeutic strategy for patients with acute schizophrenia. PPD-loaded Soluplus®/TPGS mixed micelles (PPD-S/T-MM) were prepared using the thin-film hydration method. The critical micelle concentration (CMC) of blank S/T-MM was 4.77 × 10-2 mg/mL. PPD presented much higher solubility in PPD-S/T-MM formulation than that in pure water. The particle size of blank or drug loaded S/T-MM was around 60 nm. The polydispersity index (PDI) was less than 0.1. PPD-S/T-MM presented a nearly spherical shape under transmission electron microscopy. The encapsulation efficiency (EE%) of PPD-S/T-MM was higher than 94%. Based on the analysis of XRD and DSC, it was proved that PPD was incorporated in the core of the mixed micelles as amorphous dispersion or solid solution. PPD-S/T-MM were stable when they were undergoing dilution with water and the change of environmental pH. Although PPD-S/T-MM showed lower rates to release PPD than those from PPD raw material in acidic solution, they provided faster release rates in neutral conditions than those from PPD raw material who only showed modest dissolution in the same neutral condition. This proves that PPD-S/T-MM can release PPD in a more controlled manner. After oral administration of PPD-S/T-MM (dose of PPD, 6 mg/kg) in rats, the plasma concentration of PPD increased rapidly: Tmax was 0.83 ± 0.29 h, and Cmax was 844.33 ± 93.73 ng/mL. Oral administration of PPD suspension resulted in longer Tmax and lower Cmax. The relative oral bioavailability was about 158% for PPD-S/T-MM over PPD suspension. These findings confirm that PPD-S/T-MM can provide faster release in neutral conditions and better oral absorption in rats than those from PPD raw material, which should potentially benefit patients with acute schizophrenia.

A triple enhanced permeable gold nanoraspberry designed for positive feedback interventional therapy.

Due to the unique microenvironment, nanoparticles cannot easily penetrate deeply into tumours, which decreases their therapeutic efficacy. Thus, new strategies should be developed to solve this problem and increase the efficacy of nanomedicine. In this study, gold nanoraspberries (GNRs) were constructed using ultrasmall gold nanospheres (UGNPs) with a matrix metalloproteinase (MMP)-2/9-sensitive peptide as a cross-linking agent. These UGNPs were then modified with trastuzumab (TRA) and mertansine derivatives (DM1) via the AuS bond. TRA targets the human epidermal growth factor receptor-2 (Her-2) which is overexpressed on Her-2+ breast cancer cells. The AuS bond in GNRs-DM1 can be replaced by the free sulfhydryl group of GSH, which could achieve GSH dependent redox responsive release of the drug. In the mouse model of Her-2+ breast cancer, a "positive feedback" triple enhanced penetration platform was construct to treat tumours. Firstly, near-infrared light-triggered photothermal conversion increased vascular permeability, resulting in nanoparticle penetration. Secondly, GNRs disintegrated into UGNPs in response to stimulation with MMPs. GNRs with larger particle sizes reached the tumour site through EPR effect and active targeting. Meanwhile, UGNPs with smaller particle sizes penetrated deeply into the tumour through diffusion. Thirdly, the UGNPs transformed activated cancer-associated fibroblasts to a quiescent state, which reduced intercellular pressure and promoted the penetration of the UGNPs into the interior of the tumour. In turn, an increase in the number of nanoparticles penetrating into the tumour led to a "positive feedback" loop of triple enhanced photothermal effects and further self-amplify the permeability in vivo. Interventional photothermal therapy (IPTT) was used to improve the therapeutic efficacy by reducing the laser power attenuation caused by percutaneous irradiation. The GNRs also showed excellent multimode imaging (computed tomography, photoacoustic imaging and photothermal imaging) capabilities and high anti-tumour efficacy due to efficient tumour targeting and triple enhanced deep penetration into the tumour site. Thus, these MMP-2/redox dual-responsive GNRs are promising carriers of drugs targeting human epidermal growth factor receptor 2+ breast cancer.

Emerging Antibacterial Strategies with Application of Targeting Drug Delivery System and Combined Treatment.

At present, some bacteria have developed significant resistance to almost all available antibiotics. One of the reasons that cannot be ignored is long-term exposure of bacteria to the sub-minimum inhibitory concentration (MIC) of antibiotics. Therefore, it is necessary to develop a targeted antibiotic delivery system to improve drug delivery behavior, in order to delay the generation of bacterial drug resistance. In recent years, with the continuous development of nanotechnology, various types of nanocarriers that respond to the infection microenvironment, targeting specific bacterial targets, and targeting infected cells, and so on, are gradually being used in the delivery of antibacterial agents to increase the concentration of drugs at the site of infection and reduce the side effects of drugs in normal tissues. Here, this article describes in detail the latest research progress on nanocarriers for antimicrobial, and commonly used targeted antimicrobial strategies. The advantages of the combination of nanotechnology and targeting strategies in combating bacterial infections are highlighted in this review, and the upcoming opportunities and remaining challenges in this field are rationally prospected.

Protein corona precoating on redox-responsive chitosan-based nano-carriers for improving the therapeutic effect of nucleic acid drugs.

Spontaneous formation of protein corona on chitosan-based nano-carriers is inevitable once they enter the blood, which is considered to be an important factor that weakens the delivery efficiency and therapeutic effect of nucleic acid drugs. For this, cyclic RGDyK peptide (cRGD) modified bovine serum albumin (BSA) was designed as a corona to precoat on redox-responsive chitosan-based nano-carriers (TsR NPs) before administration. The effects of the precoating corona on the pharmaceutical properties and delivery efficiency of the nano-carriers and the therapeutic effect of model siRNA (siVEGF) were investigated. The results showed that BSA-cRGD formed steady corona around TsR NPs, which enhanced targeting ability to cancer cells and reduced serum proteins adsorption. The Bc corona improved the stability and biocompatibility of TsR NPs, increased the intracellular uptake, facilitated the lysosomal escape and maintained their redox-sensitive responsiveness, resulting in enhanced gene silencing efficiency and anti-tumor proliferation effects both in vitro and in vivo.

Anti-aging derivatives of cycloastragenol produced by biotransformation.

In this study, the microbial transformation of cycloastragenol (CA) by the fungi Mucor subtilissimus AS 3.2456 and Aspergillus oryzae AS 3.407 yielded 19 metabolites. Their structures were established based on extensive NMR and HR-MS data analyses, and six of them are new compounds. The two fungal strains exhibited distinct biocatalytic features. M. subtilissimus could catalyse hydroxylation and carbonylation reactions meanwhile the fragile 9,19-cyclopropane ring remained intact. A. oryzae preferred to catalyse hydroxylation, acetylation and ring expansion reactions. These highly specific reactions are difficult to achieve by chemical synthesis, particularly under mild conditions. Furthermore, we found that most of the metabolites could significantly extend the lifespan of Caenorhabditis elegans at 50 µM. These biotransformed derivatives of CA could be potential anti-aging agents.

Long-Circulating Thermosensitive Liposomes for the Targeted Drug Delivery of Oxaliplatin.

INTRODUCTION: Oxaliplatin (L-OHP) is a well-known third-generation platinum anticancer drug with severe systemic- and neuro-toxicity. The main objective of the current research was to develop a targeted long-circulating thermosensitive smart-release liposome (LCTL) system for better therapeutic efficacy and less toxicity. METHODS: The reverse-phase evaporation method (REV) was used to prepare L-OHP loaded LCTL (L-OHP/LCTL). The physical characteristics were evaluated including encapsulation efficiency (EE), size, zeta potential and stability. The release behavior, cytotoxicity and in vivo evaluation were also carried out. RESULTS: EE of LCTL was around 25% with a uniform size distribution, and LCTL achieved almost complete release at 42°C while it was only 10% at 37°C. Moreover, the LCTL showed significantly higher cytotoxicity at 42°C than that at 37°C. The in vivo results indicated LCTL could target tumors and enhance retention for more than 24 h, thereby enhancing anti-tumor efficacy on 4T1-bearing mice. DISCUSSION: These results indicated that LCTL not only possessed a prolonged circulation time but it also enhanced accumulation and achieved selective release at the tumor sites. Conclusively, LCTL could serve as a promising carrier for oxaliplatin delivery to treat solid tumors.

Effects of amines on the formation and photodegradation of DCNM under UV/chlorine disinfection.

Investigations were conducted to examine the effects of amine type and initial concentration, free chlorine concentration, UV light intensity, pH and tert-butyl alcohol (TBA) on the formation of dichloronitromethane (DCNM) under UV/chlorine. Methylamine (MA), dimethylamine (DMA) and poly-dimethyl diallyl ammonium chloride (PolyDADMAC) were selected as the amine precursors of DCNM. And the reaction products of amines were explored through observing the contents of various nitrogen under UV/chlorine. Experimental results indicated that the higher of the intensity of UV light, the concentration of amines and free chlorine, the greater of the amount of DCNM formation; the amine substance with simple structure is more likely oxidized to form DCNM, so the potential of MA to form DCNM is the largest among three amines; the formation of DCNM decreased with increasing pH from 6.0 to 8.0; due to adding TBA into the reaction solution, halogen and hydroxyl radicals were restrained which resulted the DCNM formation decreased. In the reaction process, the formation of DCNM from amines increased at the beginning, then decreased and almost disappeared due to photodegradation. During the formation and photodegradation of DCNM, the dissolved organic nitrogen could be transformed into the ammonia-nitrogen (NH3-N) and nitrate-nitrogen (NO3--N).

siVEGF-loaded nanoparticle uptake by tumor-associated vascular endothelial cells for hepatocellular carcinoma.

Aim: This study examined nanoparticle entry into tumor-associated vascular endothelial cells during transport to hepatocellular carcinoma cells and tumors. Materials & methods: siVEGF was loaded into CS-SS-9R/BSA-cRGD nanoparticles (CBc NPs). The intracellular uptake, gene silencing efficiency, antiproliferation and antiangiogenic effect of the NPs were performed on EA.hy926 cells. In vivo antitumor and antiangiogenic effects were investigated in Bel-7402 tumor-bearing nude mice. Results: siVEGF-loaded CBc NPs entered EA.hy926 cells and suppressed their proliferation and capillary formation. The NPs also inhibited tumor proliferation and angiogenesis in tumor-bearing mice, which attributed to the downregulation of VEGF mRNA expression in tumor tissue. Conclusion: The uptake of siVEGF-loaded CBc NPs by tumor-associated vascular endothelial cells made important contributions in controlling the progression of hepatocellular carcinoma.

Eprinomectin nanoemulgel for transdermal delivery against endoparasites and ectoparasites: preparation, in vitro and in vivo evaluation.

Nanoemulgels are composed of O/W nanoemulsion and hydrogels and are considered as ideal carriers for the transdermal drug delivery because these have high affinity to load hydrophobic drugs. The stable formulation of eprinomectin (EPR) is very challenging because of it is high hydrophobic nature. In this work, we have prepared EPR loaded nanoemulgel for the treatment of endo- and ectoparasites. The surface morphology of optimized formulations was characterized by scanning electron microscopy. Additionally, skin permeability and irritation tests were conducted for in vitro safety and in vivo skin retention and pearmeation test of EPR nanoemulgel were conducted for efficacy study. Obtained results indicated that the optimized formulation had good shear-thinning behavior, bioadhesiveness properties, and are nanosized droplets with porous internal structure, which are required for topical application. Furthermore, this formulation has showed good skin permeability in comparison to suspension and has no skin irritating property. Overall, the obtained results proved that nanoemulgel is a promising carrier for transdermal drug delivery and EPR nanoemulgel is a promising formulation for the treatment of endo- and ectoparasites.

Preparation, intestinal segment stability, and mucoadhesion properties of novel thymopentin-loaded chitosan derivatives coated with poly (n-butyl) cyanoacrylate nanoparticles.

BACKGROUND: In order to develop a promising carrier for the oral delivery of proteins and peptide drugs, a novel bioadhesive nanocarrier of chitosan (CTS) derivatives coated with poly (n-butyl) cyanoacrylate nanoparticles (PBCA-NPs) was prepared in this study. METHODS: Three different thymopentin (TP5)-loaded nanoparticles were prepared in the present study. TP5-PBCA-NPs were developed by modifying an emulsion polymerization method, and CTS and chitosan-glutathione (CG) derivative-coated PBCA nanoparticles were obtained from the electrostatic interactions between CTS or CG with negatively charged PBCA nanoparticles. RESULTS: The particle sizes of TP5-PBCA-NPs, TP5-CTS-PBCA-NPs, and TP5-CG-PBCA-NPs were 212.3±6.9, 274.6±8.2, and 310.4±7.5 nm, respectively, while the respective zeta potentials were -22.6±0.76, 23.3±1.2, and 34.6±1.6 mV with encapsulation efficiencies of 79.37%±2.15%, 74.21%±2.13%, and 72.65%±1.48%, respectively. An everted intestinal ring method indicated that drug stability was remarkably improved after incorporation into the nanoparticles, especially the CG-coated nanoparticles. The mucus layer retention rates for CTS- and CG-coated nanoparticles were 1.43 and 1.83 times that of the uncoated nanoparticles, respectively, using ex vivo mucosa. The in vivo mucoadhesion study illustrated that the transfer of uncoated PBCA-NPs from the stomach to the intestine was faster than that of CTS-PBCA-NPs and CG-PBCA-NPs, while the CG-PBCA-NPs presented the best intestinal retentive characteristic. CONCLUSION: In summary, this study demonstrated the feasibility and benefit of orally delivering peptide drugs using novel CTS derivative-coated nanoparticles with optimal stability and bioadhesive properties.

Microbial hydroxylation and glycosidation of oleanolic acid by Circinella muscae and their anti-inflammatory activities.

Biotransformation of oleanolic acid (OA) by Circinella muscae AS 3.2695 was investigated. Nine hydroxylated and glycosylated metabolites (1-9) were obtained. Their structures were elucidated as 3ß,7ß-dihydroxyolean-12-en-28-oic acid (1), 3ß,7ß,21ß-trihydroxyolean-12-en-28-oic acid (2), 3ß,7α,21ß-trihydroxyolean-12-en- 28-oic acid (3), 3ß,7ß,15α-trihydroxyolean-12-en-28-oic acid (4), 7ß,15α-dihydroxy- 3-oxo-olean-12-en-28-oic acid (5), 7ß-hydroxy-3-oxo-olean-12-en-28-oic acid (6), oleanolic acid-28-O-ß-D-glucopyranosyl ester (7), 3ß,21ß-dihydroxyolean-12-en-28- oic acid-28-O-ß-D-glucopyranosyl ester (8), and 3ß,7ß,15α-trihydroxyolean-12-en- 28-oic acid-28-O-ß-D-glucopyranosyl ester (9) by spectroscopic analysis. Among them, compounds 4 and 9 were new compounds. In addition, anti-inflammatory activities were assayed and evaluated for the isolated metabolites. Most of the metabolites exhibited significant inhibitory activities on lipopolysaccharides-induced NO production in RAW 264.7 cells.