Age-related macular degeneration (AMD) is a degenerative retinal disease. AMD is divided into two major forms: dry (atrophic) AMD and wet (exudative) AMD. The most common treatment for wet AMD is intravitreal injection of anti-vascular endothelial growth factor drugs. However, the treatment can only relieve but not care, and there are some patients who aren’t adapted to this treatment of administration. The application of nanotechnology offers new strategies for improving drug delivery in AMD, where polymeric nanoparticles can provide sustained drug release, can be modified to target the lesion and increase drug target site deposition, can penetrate the ocular barrier and extend drug retention times. This paper reviews the current research advances in polymeric nanoparticles-based drug delivery systems for the treatment of AMD, providing a viable reference to the treatment of AMD.

OBJECTIVE To evaluate the safety and biodistribution characteristics of mixed activated killer (MAK) immune cells derived from the blood of tumor patients in immunodeficient mice. METHODS Immunodeficient NOG mice were injected with MAK cells 9 times via the tail vein. The mice were observed continuously for 28 d after the last administration. The clinical symptoms, body weight, food intake, hematological and serum biochemical indexes, cytokine indexes and histopathological changes in mice were investigated. In the meanwhile, the distribution characteristics of MAK cells in peripheral blood and various tissues and organs were investigated. RESULTS MAK cells had no significant effect on clinical symptoms, the injection site, body weight and food intake in mice, and could increase the level of human interferon gamma in serum of mice. MAK cells could elevate lymphocytes%, monocytes%, white blood cells and decrease basophils% in peripheral blood. Mix cell aggregates were observed in most organs. Massive expansion of MAK cells was observed in most tissues of mice after administration of MAK cells for 28 d. CONCLUSION MAK cells could proliferate and induce immune responses in immunodeficient NOG mice without obvious toxic reactions. Given the above, the data of this study can provide a reference for the non-clinical safety evaluation of related products.

Traditional Chinese medicine (TCM) decoction is a complex dispersion system, and its active components are mostly to form different phases in the form of solutes or dispersed substances, such as true solution, colloidal phase, suspension phase, etc. The active components are complex and diverse, and the formation, transformation, and transmission of each phase may affect the metabolism and action process of the pharmacodynamic components in biological bodies. However, the study on the phase differences and effective phases in TCM decoction is still in the initial stage. In this paper, we will be explored the quality basis and mechanism of TCM decoction from the perspectives of the formation, characterization, transformation, transmission and mechanism of the ordered phase in TCM decoction, and look forward to the quality research mode of TCM based on phase structure, so as to provide a reference for explaining the effect mechanism of TCM decoction from the perspective of structural TCM decoction.

OBJECTIVE To prepare and characterize scoprone-loaded PLGA microspheres. METHODS Scoprone-loaded PLGA microspheres were constructed by a O/W emulsion-solvent evaporation method.Their surface morphology, encapsulation rate and drug loading of microspheres were the main evaluation indexes. Based on single factor experiment,the optimum preparation conditions of PLGA microspheres were obtained through central composite design. RESULTS Scoprone-loaded PLGA microspheres were light yellow powder and spherical in shape with smooth surface with size 2.94 μm.Scoprone was loaded into PLGA microspheres with drug loading(4.28%)and encapsulation efficiency(47.03%). CONCLUSION Scoprone-loaded PLGA microspheres are constructed successfully. The particle size of microspheres meets the requirements of intraocular vitreous cavity injection, and has good slow-release performance under simulated in vitro environment. The preparation method is accurate and reliable, and can provide a new dosage form for the treatment of diabetic retinopathy.

OBJECTIVE To establish a new derivatization headspace gas chromatography-flame ionization detection (HS-GC-FID) method to detect the residual amount of dimethyl sulfate in neostigmine methylsulfate bulk drug. METHODS Various derivatization methods were screened and then optimized. n-Butanol was used as the derivatization agent and methylated with dimethyl sulfate at the temperature of 50 ℃, producing the derivatization product methyl n-butyl ether. The analytical column was DB-624 (0.32 mm×30 m, 1.8 μm). The column temperature was maintained at 40 ℃, holding for 8 min, then was raised to 220 ℃ at the rate of 30 ℃·min^-1, holding for 2 min. The flow rate of carrier gas nitrogen was 2.0 mL·min^-1. The detection was achieved in FID with the injection port temperature of 200 ℃ and the detector temperature of 230 ℃. RESULTS Neostigmine methylsulfate showed no false positive interference with the detection of dimethyl sulfate. The calibration curve of dimethyl sulfate had good linearity over the range of 6.066 to 151.7 μg·mL^-1 (r²=0.999 9). The average recovery of dimethyl sulfate was 99.9%, and the RSD was 2.6%(n=9). CONCLUSION This method exhibits good specificity, simplicity, and high accuracy, and it can be used for the determination of genotoxic impurity dimethyl sulfate in neostigmine methylsulfate bulk drug.

OBJECTIVE To interpret Guidance on Quality Control for Nanomedicines (interim) issued by center for drug evaluation, NMPA, and provide reference for the development of nanomedicines. METHODS By conducting a systematic review of domestic and international literature and combining background of the guidance, this paper discussed the definition and classification of nanomedicines, quality research and control strategies, process control and stability research. It also proposes points of attention in the quality control studies of nanomedicines with cases. RESULTS and CONCLUSION The special nano-size, structure and surface properties of nanomedicines may significantly change the physicochemical properties and behaviors of active pharmaceutical ingredients in vitro and in vivo, which in turn affect their safety and efficacy. Quality research spans the entire lifecycle of nanomedicines. Critical quality attributes related to nano-characteristics should be evaluated based on the type, composition and structure of nanomedicines, manufacturing process, as well as their clinical use. Risk assessment strategy based on drug evaluation should focus on the impact of the quality attributes of nanomedicines on their safety and efficacy.

OBJECTIVE To prepare liposome formulations encapsulating isovaleryl shikonin, to optimise the preparation process. METHODS The isovalerylshikonin-liposome (IsoSHK-lip) were prepared by the thin film dispersion method. The UV absorption, standard curve, precision, stability and recovery of IsoSHK-lip were investigated. A response surface optimization method was used to optimize a 3-factor, 3-level preparation scheme with A: lecithin-cholesterol mass ratio, B: lecithin-isovalerylshikonin mass ratio and C: volume of hydrated solvent as the three factors. The particle size, polymer dispersity index (PDI), Zeta potential, morphological characterisation and stability of IsoSHK-lip were also investigated for the optimal solution. RESULTS The response surface optimization predicted that the optimal preparation conditions for IsoSHK-lip were: lecithin-cholesterol mass ratio of 8.82∶1, lecithin-isovalerylshikonin mass ratio of 30.65∶1, and volume of hydrated solvent of 29.22 mL. Repeated preparation of the optimal IsoSHK-lip resulted in an average encapsulation rate of 90.03%, a mean particle size of 117.48 nm, a mean PDI of 0.246, and a mean Zeta potential of -13.59 mV. The stability experiments showed that the particle size, PDI and Zeta potential of IsoSHK-lip did not change significantly after 7 d at 4 ℃. Transmission electron microscopy showed that the IsoSHK-lip was subspherical with particle sizes in the range of 100-200 nm. CONCLUSION IsoSHK-lip is prepared by repeating the optimal results obtained by response surface methodology three times, resulting in a near spherical shape, smaller particle size, uniform particle size distribution and better stability of IsoSHK-lip, which provides the basis for subsequent pharmacological studies of dosage forms.

OBJECTIVE To prepare cepharanthine(CEP) polymer micelles and characterize them. METHODS The CEP polymer micelles were prepared by solvent evaporation method. Based on the single factor investigation, the preparation process was optimized by Box-Behnken response surface method with the entrapment efficiency and drug loading as indicators, and the particle size distribution, potential and in vitro release of the micelles were characterized. RESULTS The optimum process of CEP polymer micelle was as follows: 50 mg of MA-PEG-PLGA and 17.82 mg of CEP were dissolved in 0.25 mL of acetone, added dropwise into 14 mL of PBS solution at 60 ℃ and stirred on a magnetic stirrer at a speed of 1 000 r·min^-1 for 4 hours to obtain a clear CEP polymer micelle. The optimized CEP polymer micelles are spherical, with an average particle size of (111.37±3.51) nm, a PDI of (0.21±0.01) and a Zeta potential of (-9.78±2.15) mV. In vitro release results showed that CEP was released rapidly within 10 h, and its micelles released (79.99±4.96)% and (71.66±2.62)% respectively within 72 h, indicating that CEP could be released slowly after being made into micelles. The results of freeze-drying agent investigation showed that 0.5% poloxamer 188 had the smallest change in complex particle size after freeze-drying. The results of hemolysis test showed that the hemolysis rate was obviously reduced after CEP was made into micelles. CONCLUSION The optimized formulation and technology in this study can be used for the preparation of CEP-MA-PEG-PLGA polymer micelles, which lays a foundation for the subsequent development of CEP targeted preparations.

Triptolide (TP), also known as triptolide alcohol, is an epoxidised diterpene lactone compound extracted from the xylem of Tripterygium wilfordii Hook. f., a plant of the Weseraceae family. As the main active ingredient in Tripterygium wilfordii Hook. f. extracts, it has been proved to have immunosuppression, anti-tumor, anti-inflammation and other pharmacological effects. However, the development of triptolide has been limited due to its poor water solubility, high toxicity, obvious adverse reactions and low bioavailability. Therefore, researchers have optimised the structure of triptolide with the hope to improve its physicochemical properties. By now, the structure optimization has mainly been focused on sites like C-5,6, C-14, C-16, C-20, epoxy groups, unsaturated five-membered lactone ring. This paper summarizes the researches related to the structure optimization and their biological activity of the above reactive sites, which provides new thoughts for the structure-activity relationship and clinical application of triptolide.

As an innovative diseases treatment strategy, bionic nano-decoy system which can neutralize a variety of pathogenic substances has attracted extensive attention in the biomedical field in recent years. Compared with traditional diseases treatment methods, bionic nano-decoy system shows the characteristics of high-efficiency pathogenic molecule clearance, excellent biocompatibility and sustainable or repeated drug delivery, which make it have great application potential in the field of diseases neutralization and treatment. In this paper, the concept, characteristics, preparation technology and application scope of bionic nano-decoy system are reviewed, aiming to provide important reference for researchers and medical professionals in the design and development of new bionic nano-decoy system, in order to promote the development of this field and ultimately achieve clinical application.