Preparation and in vitro evaluation of polylactic acid nanoparticles containing arginine and glucose oxidase / 药学学报

Hydrogen peroxide (H2O2) and nitric oxide (NO) has a short half-life, low bioavailability, poor tumor targeting and systemic adverse reactions in the physiological environment. In this study, phacoemulsification and nano-precipitation were used to synthesize didecyl dimethyl ammonium bromide (DDAB)/polylactic acid nanoparticles (PLA), then L-arginine (L-Arg) and glucose oxidase (GOx)-loaded nanoparticles (GADP) were prepared, and the in vitro antitumor activity was investigated．The particle size, potential, embedding rate and the ability to produce H2O2/NO of the nanoparticles were investigated. Meanwhile, in vitro cell cytotoxicity against human hepatoma cells (HepG2) was evaluated．The results showed that the prepared L-Arg-DDAB/PLA (ADP) nanoparticles were spherical particles. And the particle size and zeta potential were (225.7 ± 6.33) nm and (+23.5 ± 0.12) mV, respectively. The adsorption rate of GOx was 87.23% ± 0.02%. The drug loading of L-Arg was 15.6% ± 0.22%. The pH value of glucose solution and the amount of H2O2 showed that GADP had good catalytic activity. In vitro cytotoxicity experiments showed that blank nanoparticles were nontoxic, while the drug-loaded nanoparticles presented enhanced antitumor effect on HepG2 cells. And can inhibit tumor cell migration. The low dose nano-scale NO delivery system GADP can effectively inhibit the migration of tumor cells and kill tumor cells, thus producing therapeutic benefits.

Preparation and properties of heparosan polysaccharide-vitamin E succinate polymer micelles / 药学学报

Due to the advantages of polymer micelles and the anticancer activity of doxorubicin (DOX), the polymer micelle of DOX is expected to be used for drug delivery in anticancer applications. As a biocompatible and biodegradable polymer, amphiphilic copolymer heparosan-adipic dihydrazide-vitamin E succinate (KV) can be self-assembled to form micelles with core-shell structure in aqueous phase. In this article, KV conjugates with two different degrees of substitution (DS) were synthesized to load DOX and were characterized by 1H NMR. The size distribution, morphology, zeta potential and release behavior in vitro of the DOX-loaded micelles were studied. In vitro cytotoxicity was investigated by MTT assay against MGC80-3 and COS7 cells. The cellular uptake of the DOX-loaded micelles was observed by fluorescence microscopy and flow cytometry. The 1H NMR spectra results confirmed the KV polymers were successfully conjugated and the degree of VES grafted on heparosan polysaccharide were 12% and 25%. Briefly, the micelles with two different DS were expressed as KV12 and KV25. The DOX-loaded micelles could resist serum adsorption because of the negative charge on the surface. The average particle size measured by dynamic light scattering (DLS) method was 140-150 nm and the TEM results indicated that the morphology of DOX-loaded micelles were spherical. The encapsulation efficiency and drug loading were 80% and 10%-15%, respectively. The DOX-loaded micelles had sustained release behavior and the cumulative release of DOX/KV12 was slightly higher than DOX/KV25. Moreover, the viabilities of cells which were co-incubated with blank micelles were greater than 90%. It is clear that the blank micelles almost non-toxic to both cells. The IC50 of drug-loaded micelles against COS7 cells was much higher than that of MGC80-3 cells and the DOX/KV12 exhibited greater cytotoxicity. The cellular uptake of DOX/KV on MGC80-3 was greater than COS7 cells. In this study, KV polymer micelles have a sustained drug release activity and have a good selectivity to tumor cells, so it would be a potential carrier in drug delivery.

Preparation and characterization of terminal modified hyaluronic acid copolymer micelles / 中国药学杂志

OBJECTIVE: To synthesize hyaluronic acid-octadecene (HOY) copolymers by terminal thiolation modification of hyaluronic acid (HA), prepare doxorubicin-loaded micelles and investigate its pharmaceutical characteristics. METHODS: HOY copolymers were synthesized through Michael addition reaction. The doxorubicin-loaded copolymer micelles were prepared with ultrasonic method, then the particle size, Zeta potential, encapsulation efficiency, drug loading efficiency and in vitro release behavior were studied. RESULTS: HOY copolymers were synthesized successfully. The particle size and Zeta potential of the drug-loaded micelles were (237.2±2.7) nm and (-22.37±0.38) mV, and the encapsulation efficiency and drug loading rate were (89.8±0.011)% and (5.4±0.007)%, respectively. Moreover, the accumulative release of doxorubicin in vitro was about 70% in 48 h, indicating that the drug was released slowly from the micelles. CONCLUSION: This study develops a new micellar system based on terminal modified HA, and provides a reference for the study of HA nanocarrier.

Hyaluronic acid-based carriers for tumor targeted delivery system / 药学学报

Hyaluronic acid (HA) as anticancer drug carrier has become the new hot point in the field of tumor-targeted drugs delivery system in recent years. Tumor therapeutic agents could be transmitted into cells because of hyaluronic acid innate ability to recognize specific cellular receptors that overexpressed on tumor cells surface. This review introduces the basic properties and physiology foundation of hyaluronic acid. Recent research developments based on different forms of HA tumor-targeted drugs delivery systems are reviewed in particular.

Preparation and characterization of oxaliplatin-loaded nanostructured lipid carriers / 药学学报

Oxaliplatin-loaded nanostuctured lipid carriers (OP-NLC) were prepared by ultrasonic emulsification method. And its optimal prescription was selected by orthogonal design. The laser light scattering technique, zeta potential analyzer, TEM, DSC, XRD and HPLC were employed to study the physicochemical parameters of OP-NLC, which displayed in terms of particle size, zeta potential, crystalline, drug loading and encapsulation efficiency. The results showed that OP-NLC had an average diameter of (111 +/- 20) nm, zeta potential of (-27.4 +/- 13.1) mV, encapsulation efficiency of (77.4 +/- 2.5) % and drug content of (0.8 +/- 1.5) mg mL(-1). TEM, DSC and XRD indicated that OP-NLC was spherical and the drug was dispersed as nanoparticles by means of non-crystalline. The in vitro release test showed that the drug could be sustained-released from NLC in buffer solution (pH 4.5) after a burst release in initial phase.