Electrophoresis, Capillary ; methods ; Humans ; Micelles ; Paraquat ; blood

Polymeric hydrogels have been widely researched as drug delivery systems, wound dressings and tissue engineering scaffolds due to their unique properties such as good biocompatibility, shaping ability and similar properties to extracellular matrix. However, further development of conventional hydrogels for biomedical applications is still limited by their poor mechanical properties and self-healing properties. Currently, nanocomposite hydrogels with excellent properties and customized functions can be obtained by introducing nanoparticles into their network, and different types of nanoparticles, including carbon-based, polymer-based, inorganic-based and metal-based nanoparticle, are commonly used. Nanocomposite hydrogels incorporated with polymeric micelles can not only enhance the mechanical properties, self-healing properties and chemical properties of hydrogels, but also improve the
Biocompatible Materials ; Hydrogels ; Micelles ; Nanocomposites ; Polymers

OBJECTIVETo synthesize three amphiphilic molecules (TEG-R1, TEG-R2, TEG-R3), with branched oligo polyethylene glycol as hydrophilic fractions and aliphatic chains (containing six, eight and twelve carbon atoms respectively) as hydrophobic fractions, and study them as insoluble drug vectors.

METHODThree compounds were successfully through acylation, substitution reaction, reduction reaction and esterification. Their structures were verified by NMR analysis; and the critical micelle concentrations (CMC) of TEG-R1, TEG-R2, TEG-R3 were determined by pyrene fluorescence probe spectrometry. Transmission electronic microscopy (TEM) photos displayed the state of the aqueous solution. The self-assembly solution evaporation method was adopted to prepare drug loading podophyllotoxin micelles, and characterize their grain size, in order to detect the hemolysis of the three amphiphilic molecules.

RESULTNuclear magnetism showed the successful synthesis of three amphiphilic molecules, with critical micelle concentrations of TEG-R1, TEG-R2, TEG-R3 of 50, 50, 10 mg x L(1), respectively. Transmission electronic microscopy (TEM) photos displayed a spherical-like state, with diameter of 20-50 nm. All of the three amphiphilic molecules could be prepared into drug-loading micelles, with the range of grain sizes between 100-200 nm. Hemdytic experiment showed that, among the amphiphilic molecules of the graft six-carbon aliphatic chain, TEG-R1 could not cause hemolysis.

CONCLUSIONAll of the three amphiphilic molecules are micellized in water solution, and can be used as insoluble drug vectors. Among them, TEG-R1 could not cause hemolysis, and is expected to become a new-type drug vector.

Drug Carriers ; chemical synthesis ; chemistry ; Hydrophobic and Hydrophilic Interactions ; Micelles ; Microscopy, Electron, Transmission ; Polymers ; chemical synthesis ; chemistry

The objectives of this study are to prepare resveratrol loaded mixed micelles composed of poloxamer 403 and poloxamer 407, and optimize the formulation in order to achieve higher drug solubility and sustained drug release. Firstly, a thin-film hydration method was utilized to prepare the micelles. By using drug-loading, encapsulation yield and particle size of the micelles as criteria, influence of three variables, namely poloxamer 407 mass fraction, amount of water and feeding of resveratrol, on the quality of the micelles was optimized with a central composite design method. Steady fluorescence measurement was carried out to evaluate the critical micelle concentration of the carriers. Micelle stability upon dilution with simulated gastric fluid and simulated intestinal fluid was investigated. The in vitro release of resveratrol from the mixed micelles was monitored by dialysis method. It was observed that the particle size of the optimized micelle formulation was 24 nm, with drug-loading 11.78%, and encapsulation yield 82.51%. The mixed micelles increased the solubility of resveratrol for about 197 times. Moreover, the mixed micelles had a low critical micelle concentration of 0.05 mg · mL(-1) in water and no apparent changes in particle size and drug content were observed upon micelles dilution, indicating improved kinetic stability. Resveratrol was released from the micelles in a controlled manner for over 20 h, and the release process can be well described by Higuchi equation. Therefore, resveratrol-loaded poloxamer 403/407 mixed micelles could improve the solubility of resveratrol significantly and sustained drug release behavior can be achieved.
Drug Carriers ; chemistry ; Fluorescence ; Kinetics ; Micelles ; Particle Size ; Poloxamer ; chemistry ; Solubility ; Stilbenes ; chemistry ; Water

OBJECTIVETo prepare puerarin deoxycholate/phospholipid mixed micelle to increase the solubility of puerarin.

METHODSodium deoxycholate and soybean phospholipids were used to prepare puerarin mixed micelle through orthogonal design experiments. With the solubility, shape and particle size as the response indexes, the preparing process of puerarin mixed micelle was optimized.

RESULTThe optimized process for the puerarin deoxycholate/phospholipid mixed micelle was that the puerarin, soya phosphatidylcholine and sodium deoxycholate with the mole ratio of 3:2:4 should be dissolved in methanol-chloroform (1:1), and the solvents should be evaporated rotatively at 30 degrees C. The particle diameter of the mixed micelle was (64.8 +/- 13) nm (volume-weighted particle size distribution), and the solubility was 0.811 1 g x L(-1) in water at the room temperature, which was 22.3 times as that of the raw puerarin (0.036 4 g x L-1).

CONCLUSIONThe puerarin deoxycholate/phospholipid mixed micelle can improve the solubility of puerarin significantly.

Deoxycholic Acid ; chemistry ; Isoflavones ; chemistry ; Micelles ; Particle Size ; Phospholipids ; chemistry ; Plant Extracts ; chemistry ; Solubility

This study aimed to prepare evodiamine-glycyrrhizic acid(EVO-GL) micelles to enhance the anti-hepatic fibrosis activity of evodiamine. Firstly, EVO-GL micelles were prepared with use of thin film dispersion method. With particle size, encapsulation efficiency, loading capacity of micelles and the solubility of evodiamine as the indexes, the effect of different factors on micelles was observed to screen the optimal preparation methods and process. Then the pharmaceutical properties and the therapeutic effects of EVO-GL micelles prepared by optimal process were evaluated on CCl_4-induced hepatic fibrosis. The results showed that the micelles prepared by the thin film dispersion method had an even size, with an average particle size of(130.80±12.40)nm, Zeta potential of(-41.61±3.12) mV, encapsulation efficiency of 91.23%±1.22%, drug loading of 8.42%±0.71%, high storage stability at 4 ℃ in 3 months, and slow in vitro release. Experimental results in the treatment of CCl_4-induced hepatic fibrosis in rats showed that EVO-GL micelles had a synergistic anti-hepatic fibrosis effect, which significantly reduced the liver function index of hepatic fibrosis rats. In conclusion, the EVO-GL micelles prepared with glycyrrhizic acid as a carrier would have a potential application prospect for the treatment of hepatic fibrosis.
Animals ; Drug Carriers ; Glycyrrhizic Acid ; Liver Cirrhosis ; Micelles ; Particle Size ; Quinazolines ; Rats ; Solubility

This study aimed to prepare andrographolide (AP)-loaded glycyrrhizic acid (GA) micelles (AP-GA)-PMs to enhance the solubility and anti-tumor effect of andrographolide. Firstly, andrographolide (AP) was used as the model drug and glycyrrhizic acid (GA) as carriers to prepare (AP-GA)-PMs. Then the preparation methods and the ratios of drug and carrier were screened and optimized based on particle size, encapsulation efficiency (EE) and loading capacity of micelles. Finally, the pharmaceutical characters and the inhibition rate on HepG2 cells were evaluated on the (AP-GA)-PMs prepared by optimal process. The results showed that the prepared micelles under the optimal process had a nanosize of (127.11±1.38) nm, zeta potential of (-24.01±0.55) mV, the entrapment efficiency rate of (92.01±4.02)% , the drug loading rate of (51.44±1.24)% and high storage stability at 4 °C in 30 d, with slow but highly stable release. Moreover, (AP-GA)-PMs with the IC₅₀ value of 19.25 mg·L⁻¹ had a more synergistic and better anti-tumor effect in comparison with AP (IC₅₀=122.40 mg·L⁻¹) on HepG2 cells (P<0.01). In conclusion, the (AP-GA)-PMs prepared with glycyrrhizic acid as a carrier had a small particle size, large drug loading capacity, and high stability, and could significantly improve the anti-tumor effects of AP.
Antineoplastic Agents ; pharmacology ; Diterpenes ; pharmacology ; Drug Carriers ; chemistry ; Glycyrrhizic Acid ; chemistry ; Micelles ; Particle Size ; Polymers

The present study determined five saponins in Xuesaitong Dropping Pills(XDP) by micellar electrokinetic chromatography(MEKC), and evaluated between-batch consistency by MEKC fingerprints and similarity analysis. A background buffer was composed of 20 mmol·L~(-1) sodium tetraborate-20 mmol·L~(-1) boric acid solution(pH 8.5), 55 mmol·L~(-1) sodium dodecyl sulfate(SDS), 23 mmol·L~(-1) β-cyclodextrin, and 13% isopropyl alcohol. All separations were performed at 25 ℃,20 kV and the detection wavelength was set at 203 nm. The separation channel was a fused silica capillary with a dimension of 75 μm I.D. and a total length of 50.2 cm(effective length of 40.0 cm). The contents of notoginsenoside R_1, and ginsenosides Rg_1, Re, Rb_1, Rd were determined with their quality control ranges set. The fingerprints of XDP were established and the between-batch consistency was evaluated by similarity analysis. The contents of five saponins from the 19 batches of XDP were stable in the fixed ranges. Statistical analysis was carried out on the results of multiple batches of samples, and the specific quality control ranges were recommended as follows: notoginsenoside R_1 21.92-34.16 mg·g~(-1), ginsenosides Rg_1 83.54-131.78 mg·g~(-1), ginsenosides Re 13.58-19.82 mg·g~(-1), ginsenosides Rb_1 89.40-129.90 mg·g~(-1), and ginsenosides Rd 22.34-35.67 mg·g~(-1). Eleven characteristic peaks were identified in the fingerprints. Five peaks, notoginsenoside R_1 and ginsenosides Rg_1, Re, Rb_1, Rd, were identified with reference standards. The similarities of the 19 batches of samples were all above 0.988, indicating good between-batch consistency. This method is green and simple, and can be used for the quantitative determination and quality evaluation of XDP. It can also provide references for the quality control of other Chinese medicinal dripping pills.
Chromatography, Micellar Electrokinetic Capillary ; Drugs, Chinese Herbal ; Micelles ; Quality Control ; Saponins

The blood-brain barrier(BBB), a protective barrier between brain tissues and brain capillaries, can prevent drugs from entering the brain tissues to exert the effect, which greatly increases the difficulty in treating brain diseases. The drug delivery system across the BBB can allow efficient drug delivery across the BBB by virtue of carriers and formulations, thereby enhancing the therapeutic effect of drugs on brain tissue diseases. Liposomes and micelles have been extensively studied with advances in the targeted therapy across the BBB for the brain due to their unique structures and drug delivery advantages. This study summarized the research status of liposome and micelle drug delivery systems across the BBB based on the literature in recent years and analyzed their application advantages and mechanism in terms of trans-BBB capability, targeting, and safety. Moreover, the problems and possible countermeasures in the research on trans-BBB liposomes and micelles were discussed according to the current clinical translation, which may provide refe-rences and ideas for the development of trans-BBB targeted nano-drugs.
Humans ; Blood-Brain Barrier ; Liposomes ; Micelles ; Drug Delivery Systems ; Biological Transport ; Brain ; Brain Diseases

Polymer micelles formed by self-assembly of amphiphilic polymers are widely used in drug delivery, gene delivery and biosensors, due to their special hydrophobic core/hydrophilic shell structure and nanoscale. However, the structural stability of polymer micelles can be affected strongly by environmental factors, such as temperature, pH, shear force in the blood and interaction with non-target cells, leading to degradations and drug leakage as drug carriers. Therefore, researches on the structural integrity and in vivo distribution of micelle-based carriers are very important for evaluating their therapeutic effect and clinical feasibility. At present, fluorescence resonance energy transfer (FRET) technology has been widely used in real-time monitoring of aggregation, dissociation and distribution of polymer micelles ( in vitro and in vivo). In this review, the polymer micelles, characteristics of FRET technology, structure and properties of the FRET-polymer micelles are briefly introduced. Then, methods and mechanism for combinations of several commonly used fluorescent probes into polymer micelles structures, and progresses on the stability and distribution studies of FRET-polymer micelles ( in vitro and in vivo) as drug carriers are reviewed, and current challenges of FRET technology and future directions are discussed.
Micelles ; Drug Carriers/chemistry* ; Polymers/chemistry* ; Fluorescence Resonance Energy Transfer ; Polyethylene Glycols/chemistry*