A "Trojan Horse" Strategy: The Preparation of Bile Acid-Modifying Irinotecan Hydrochloride Nanoliposomes for Liver-Targeted Anticancer Drug Delivery System Study.

The bile acid transport system is a natural physiological cycling process between the liver and the small intestine, occurring approximately 6-15 times during the day. There are various bile acid transporter proteins on hepatocytes that specifically recognize bile acids for transport. Therefore, in this paper, a novel liposome, cholic acid-modified irinotecan hydrochloride liposomes (named CA-CPT-11-Lip), was prepared based on the "Trojan horse" strategy. The liposomes preparation process was optimized, and some important quality indicators were investigated. The distribution of irinotecan hydrochloride in mice was then analyzed by high-performance liquid chromatography (HPLC), and the toxicity of liposomes to hepatocellular carcinoma cells (HepG-2) was evaluated in vitro. As a result, CA-CPT-11-Lip was successfully prepared. It was spherical with a particle size of 154.16 ± 4.92 nm, and the drug loading and encapsulation efficiency were 3.72 ± 0.04% and 82.04 ± 1.38%, respectively. Compared with the conventional liposomes (without cholic acid modification, named CPT-11-Lip), CA-CPT-11-Lip had a smaller particle size and higher encapsulation efficiency, and the drug accumulation in the liver was more efficient, enhancing the anti-hepatocellular carcinoma activity of irinotecan hydrochloride. The novel nanoliposome modified by cholic acid may help to expand the application of irinotecan hydrochloride in the treatment of hepatocellular carcinoma and construct the drug delivery system mode of drug liver targeting.

Dual Drug-Loaded Nanoliposomes Encapsulating Curcumin and 5-Fluorouracil with Advanced Medicinal Applications: Self-Monitoring and Antitumor Therapy.

Due to the presence of physiological barriers, it is difficult to achieve the desired therapeutic efficacy of drugs; thus, it is necessary to develop an efficient drug delivery system that enables advanced functions such as self-monitoring. Curcumin (CUR) is a naturally functional polyphenol whose effectiveness is limited by poor solubility and low bioavailability, and its natural fluorescent properties are often overlooked. Therefore, we aimed to improve the antitumor activity and drug uptake monitoring by simultaneously delivering CUR and 5-Fluorouracil (5-FU) in the form of liposomes. In this study, dual drug-loaded liposomes (FC-DP-Lip) encapsulating CUR and 5-FU were prepared by the thin-film hydration method; their physicochemical properties were characterized; and their biosafety, drug uptake distribution in vivo, and tumor cell toxicity were evaluated. The results showed that the nanoliposome FC-DP-Lip showed good morphology, stability, and drug encapsulation efficiency. It showed good biocompatibility, with no side effects on zebrafish embryonic development. In vivo uptake in zebrafish showed that FC-DP-Lip has a long circulation time and presents gastrointestinal accumulation. In addition, FC-DP-Lip was cytotoxic against a variety of cancer cells. This work showed that FC-DP-Lip nanoliposomes can enhance the toxicity of 5-FU to cancer cells, demonstrating safety and efficiency, and enabling real-time self-monitoring functions.

Nano-Liposomes Double Loaded with Curcumin and Tetrandrine: Preparation, Characterization, Hepatotoxicity and Anti-Tumor Effects.

(1) Background: Curcumin (CUR) and tetrandrine (TET) are natural compounds with various bioactivities, but have problems with low solubility, stability, and absorption rate, resulting in low bioavailability, and limited applications in food, medicine, and other fields. It is very important to improve the solubility while maintaining the high activity of drugs. Liposomes are micro-vesicles synthesized from cholesterol and lecithin. With high biocompatibility and biodegradability, liposomes can significantly improve drug solubility, efficacy, and bioavailability. (2) Methods: In this work, CUR and TET were encapsulated with nano-liposomes and g DSPE-MPEG 2000 (DP)was added as a stabilizer to achieve better physicochemical properties, biosafety, and anti-tumor effects. (3) Results: The nano-liposome (CT-DP-Lip) showed stable particle size (under 100 nm) under different conditions, high solubility, drug encapsulation efficiency (EE), loading capacity (LC), release rate in vitro, and stability. In addition, in vivo studies demonstrated CT-DP-Lip had no significant toxicity on zebrafish. Tumor cytotoxicity test showed that CT-DP-Lip had a strong inhibitory effect on a variety of cancer cells. (4) Conclusions: This work showed that nano-liposomes can significantly improve the physical and chemical properties of CUR and TET and make them safer and more efficient.

Carboxylated cellulose nanocrystals with chiral nematic property from cotton by dicarboxylic acid hydrolysis.

Carboxylated cellulose nanocrystals (CNCs) were produced from cotton linter using a mixture of a dicarboxylic acid (maleic acid or succinic acid) and its corresponding anhydride with or without catalyst in acetic acid as solvent. The low solubilities of these dicarboxylic acids can ease chemical recovery and decrease environmental impact (especailly maleic acid is a U.S. FDA approved indirect food additive (21CFR175-177)) and capital costs compared with the conventional concentrated sulfuric acid hydrolysis for producing CNCs. The dicarboxylic-acid-produced CNCs (DC-CNCs) contained surface carboxyl groups of approximately 0.5 mmol/g, with ranges of dimensions of 50-150 nm in diameter and 50-700 nm in length. Birefringence was observed in the DC-CNC suspensions above critical concentrations. However, fingerprint texture was only observed in the DC-CNC suspensions produced with catalyst p-toluenesulfonic acid. Scanning electron microscopy images of the cross section of DC-CNC films revealed a periodic ordered multilayer structure. DC-CNCs were also produced using recycled dicarboxylic acids.

Transmission of aerosolized seasonal H1N1 influenza A to ferrets.

Influenza virus is a major cause of morbidity and mortality worldwide, yet little quantitative understanding of transmission is available to guide evidence-based public health practice. Recent studies of influenza non-contact transmission between ferrets and guinea pigs have provided insights into the relative transmission efficiencies of pandemic and seasonal strains, but the infecting dose and subsequent contagion has not been quantified for most strains. In order to measure the aerosol infectious dose for 50% (aID(50)) of seronegative ferrets, seasonal influenza virus was nebulized into an exposure chamber with controlled airflow limiting inhalation to airborne particles less than 5 µm diameter. Airborne virus was collected by liquid impinger and Teflon filters during nebulization of varying doses of aerosolized virus. Since culturable virus was accurately captured on filters only up to 20 minutes, airborne viral RNA collected during 1-hour exposures was quantified by two assays, a high-throughput RT-PCR/mass spectrometry assay detecting 6 genome segments (Ibis T5000™ Biosensor system) and a standard real time RT-qPCR assay. Using the more sensitive T5000 assay, the aID(50) for A/New Caledonia/20/99 (H1N1) was approximately 4 infectious virus particles under the exposure conditions used. Although seroconversion and sustained levels of viral RNA in upper airway secretions suggested established mucosal infection, viral cultures were almost always negative. Thus after inhalation, this seasonal H1N1 virus may replicate less efficiently than H3N2 virus after mucosal deposition and exhibit less contagion after aerosol exposure.