The preparation and characterisation of tasteless core-shell clarithromycin microcapsules.

This study aims to fabricate core-shell clarithromycin (CAM) microcapsules to cover up the bitter taste of CAM by spray drying with aqueous polymer dispersion. Water dispersion of Eudragit EPO and Surelease® were innovatively used to encapsulate CAM into microcapsules via a one-step spray-drying method. The inlet air temperature, airflow rate, CAM-polymer ratio, and particle size of CAM were optimised based on drug content and T6% (the time taken for the drug to release equal to 6% w/w). The powder properties were assessed by measuring particle size and microstructure using SEM, FT-IR, and PXRD. Furthermore, selected batch was assessed for their drug content, encapsulation efficiency, in vitro release, bitterness, and stability studies. EPO-Surelease® (1: 4) microcapsules had an average diameter (D50) of 37.69 ± 3.61 µm with a span of 2.395. The drug contents and encapsulation efficiency of EPO-Surelease®(1:4) were 10.89% and 63.7%, respectively. EPO-Surelease® (1:4) microcapsules prepared by spray drying with aqueous polymer dispersion can effectively mask the bitter taste of CAM.

mPEG5k- b-PLGA2k/PCL3.4k/MCT Mixed Micelles as Carriers of Disulfiram for Improving Plasma Stability and Antitumor Effect in Vivo.

The clinical application of disulfiram (DSF) in cancer treatments is hindered by its rapid degradation in the blood circulation. In this study, methoxy poly(ethylene glycol)- b-poly(lactide- co-glycolide)/poly(ε-caprolactone) (mPEG5k- b-PLGA2k/PCL3.4k) micelles were developed for encapsulation of DSF by using the emulsification-solvent diffusion method. Medium chain triglyceride (MCT) was incorporated into the mixed polymeric micelles to improve drug loading by reducing the core crystallinity. Differential scanning calorimetry (DSC) results implied that DSF is likely present in an amorphous form within the micelles, and is well dispersed. DSF is encapsulated within the core and the reservoir is stabilized by the hydrophilic shell to prevent rapid diffusion of DSF from the core. The DSF mixed micelles (DSF-MMs) showed good drug loading (5.90%) and a well-controlled particle size (86.4 ± 13.2 nm). The mixed micelles efficiently protected DSF from degradation in plasma, with 58% remaining after 48 h, while almost 90% of DSF was degraded after the same period for the DSF solution (DSF-sol), which was used as a control. The pharmacokinetics study showed that the maximum plasma concentration and bioavailability of DSF were improved by using the DSF-MMs (2 and 2.5 times that of the DSF-sol). The TIRs (tumor inhibition rates) of 5-FU, DSF-sol, and DSF-MMs were 63.46, 19.57, and 69.98%, respectively, implying that DSF-MMs slowed the growth of a H22 xenograft tumor model effectively.

Sphingomyelin-based PEGylation Cu (DDC)2 liposomes prepared via the dual function of Cu2+ for cancer therapy: Facilitating DDC loading and exerting synergistic antitumor effects.

The old alcohol-aversion drug disulfiram (DSF) has aroused wide attention as a drug repurposing strategy in terms of cancer therapy because of the high antitumor efficacy in combination with copper ion. However, numerous defects of DSF (e.g., the short half-life and acid instability) have limited the application in cancer treatment. Cu (DDC)2, the complex of diethyldithiocarbamate (DDC, DSF metabolite) and Cu2+, have been proven as the vital active component on cancer, which have aroused the attention of researchers from DSF to Cu (DDC)2. However, the poor water solubility of Cu (DDC)2 increase more difficulties to the treatment and in-depth investigations of Cu (DDC)2. In this study, sphingomyelin (SM)-based PEGylated liposomes (SM/Chol/DSPE-mPEG2000 (55:40:5, mole%)) were produced as the carriers for Cu (DDC)2 delivery to enhance the water solubility. DDC was added to Cu-containing liposomes with a higher encapsulation efficiency of more than 90%, and it reacted with Cu2+ to synthesize Cu (DDC)2. Due to the high phase transition temperature of SM and strong intermolecular hydrogen bonds with cholesterol, SM-based liposomes would be conducive to enhancing the stability of Cu (DDC)2 and preventing drug leakage during delivery. As proven by pharmacokinetic studies, loading Cu (DDC)2 into liposomes improve bioavailability, and the area under the curve (AUC0-t) and the mean elimination half-life (t1/2) increased 1.9-time and 1.3-time to those of free Cu (DDC)2, respectively. Furthermore, the anticancer effect of Cu (DDC)2 was enhanced by the liposomal encapsulation, thus resulting in remarkable cell apoptosis in vitro and a tumor-inhibiting rate of 77.88% in vivo. Thus, it was concluded that Cu (DDC)2 liposomes could be promising in cancer treatment.

Two-step fabricating micelle-like nanoparticles of cisplatin with the 'real' long circulation and high bioavailability for cancer therapy.

Cisplatin is a widely used anticancer drug for various solid tumors. However, the serious adverse effects caused by systemic distribution limit its wide use. In this study, we intend to use biocompatible materials polyethyleneimine (PEI) and poly(L-glutamic acid)-g-methoxy poly(ethylene glycol) (PLG-g-PEG) to construct nanoparticles to enhance the efficacy of cisplatin and reduce its side effects. The micelle-like nanoparticles were fabricated by a simple two-step method, with a core consisting of PEI and cisplatin and a PLG-g-mPEG coating layer. The obtained nanoparticles have a small particle size (41.79 nm) and high drug loading (16.43%). The coated nanoparticles (NP-II) strengthened the structure of PEI and cisplatin complex (NP-I) and slowed the drug release for less than 20% at pH 7.4 PBS in 24 h. Therefore, it could effectively inhibit the binding of free drug and plasma proteins to achieve the long circulation, and the bioavailability could be increased to about 600% and 285% of cisplatin solution and NP-I respectively. Besides, the cellular uptake of NP-II was enhanced in the acidic tumor microenvironment due to the detachment of coating layer and the increase of positive zeta potential of nanoparticles, which was benefit to reduce the side effect of cisplatin to normal cells. In vivo pharmacodynamic experiments also showed that NP-II improved the efficacy and reduced side effects compared to the cisplatin solution. In conclusion, the two-step fabricating micelle-like nanoparticles with the improved therapeutic efficiency and reduced side effects show great potential for cancer chemotherapy.