Preparation and Primary Bioactivity Evaluation of Novel Water-Soluble Curcumin-Loaded Polymeric Micelles Fabricated with Chitooligosaccharides and Pluronic F-68.

Curcumin (CU) is a bioactive compound extracted from turmeric and has various advantages. However, the benefit of CU is limited by its low water solubility (11 ng/mL). This research aimed to fabricate a water-soluble CU nano-formulation with chitooligosaccharides (COS) and pluronic F-68 (PF) utilizing the polymeric micelle method. The optimized curcumin-loaded chitooligosaccharides/pluronic F-68 micelles (COSPFCU) exhibited high encapsulation efficiency and loading capacity (75.57 ± 2.35% and 10.32 ± 0.59%, respectively). The hydrodynamic diameter of lyophilized COSPFCU was 73.89 ± 11.69 nm with a polydispersity index below 0.3. The COSPFCU could be completely redispersed in water and showed high DPPH scavenging ability. Meanwhile, COSPFCU could significantly reduce the cytotoxicity of the RAW 264.7 cells compared to native CU. Furthermore, COSPFCU improved the inhibition of NO release activity at 72.83 ± 2.37% but 33.20 ± 3.41% for the CU, with a low cytotoxicity concentration in the RAW 264.7 cells.

The development of multifunctional sulfated polyguluronic acid-based polymeric micelles for anticancer drug delivery.

Numerous disseminated tumor cells specifically overexpress P-selectin. Therefore, it was thought to be a potential target for tumor therapy. Herein, we described a novel P-selectin-targeted glycosyl ligand-sulfated polyguluronic acid (PGS), as an oriented carrier of P-selectin-targeted drug delivery system. Specifically, the PGS-SS-DOX polymeric micelles were constructed to confirm the practicability of the PGS carrier as a new P-selectin-targeted ligand. PGS-SS-DOX micelles comprised P-selectin-targeted PGS, doxorubicin (DOX) as an anticarcinogen, and pH/redox dual-sensitive bio-linker facilitating drug release in tumor tissues. In vitro and in vivo data showed that PGS-SS-DOX micelles significantly increased tumor cell killing capacity and exhibited a favorable biocompatibility comparison with Free-DOX. This work proved that PGS was an ideal low immunogenic, biodegradable drug carrier for the delivery of anti-cancer drugs. The facile PGS-SS-drug micelle system provided enormous opportunities for treating disseminated tumors utilizing many irreplaceable anticarcinogens.

Inhibitory activities of alginate phosphate and sulfate derivatives against SARS-CoV-2 in vitro.

Alginate derivatives have been demonstrated remarkable antiviral activities. Here we firstly identified polymannuronate phosphate (PMP) as a highly potential anti-SARS-CoV-2 agent. The structure-activity relationship showed polymannuronate monophosphate (PMPD, Mw: 5.8 kDa, P%: 8.7 %) was the most effective component to block the interaction of spike to ACE2 with an IC50 of 85.5 nM. Surface plasmon resonance study indicated that PMPD could bind to spike receptor binding domain (RBD) with the KD value of 78.59 nM. Molecular docking further suggested that the probable binding site of PMPD to spike RBD protein is the interaction interface between spike and ACE2. PMPD has the potential to inhibit the SARS-CoV-2 infection in an independent manner of heparan sulfate proteoglycans. In addition, polyguluronate sulfate (PGS) and propylene glycol alginate sodium sulfate (PSS) unexpectedly showed 3CLpro inhibition with an IC50 of 1.20 µM and 1.42 µM respectively. The polyguluronate backbone and sulfate group played pivotal roles in the 3CLpro inhibition. Overall, this study revealed the potential of PMPD as a novel agent against SARS-CoV-2. It also provided a theoretical basis for further study on the role of PGS and PSS as 3CLpro inhibitors.

Preparation and Evaluation of a Self-Nanoemulsifying Drug Delivery System Loaded with Heparin Phospholipid Complex.

A self-nanoemulsifying drug delivery system (SNEDDS) was developed to enhance the absorption of heparin after oral administration, in which heparin was compounded with phospholipids to achieve better fat solubility in the form of heparin-phospholipid (HEP-Pc) complex. HEP-Pc complex was prepared using the solvent evaporation method, which increased the solubility of heparin in n-octanol. The successful preparation of HEP-Pc complex was confirmed by differential scanning calorimetry (DSC), Fourier-transform infrared (FT-IR) spectroscopy, NMR, and SEM. A heparin lipid microemulsion (HEP-LM) was prepared by high-pressure homogenization and characterized. HEP-LM can enhance the absorption of heparin after oral administration, significantly prolong activated partial thromboplastin time (APTT) and thrombin time (TT) in mice, and reduce fibrinogen (FIB) content. All these outcomes indicate that HEP-LM has great potential as an oral heparin formulation.