Progress in the study of targeted drug delivery systems for cancer stem cells / 药学学报

The discovery, sorting and identification methods as well as targeted drug delivery systems for cancer stem cells (CSCs) have been reviewed by consulting the recent research papers. CSCs have been believed to be responsible for the occurrence and development of chemo-resistance, leading to the failure of chemotherapy. Much progress has been made in the approaches for CSCs targeting drug delivery systems. The understanding and targeted drug delivery systems for CSCs are promising to provide an alternative for cancer therapy.

The characterisitics of temperature/pH sensitive block copolymer micelles in vitro / 药学学报

The dialysis method was employed to prepare blank and doxorubicin (DOX) loaded micelles formed by temperature- and pH- sensitive polyhistidine-co-polyDL-lactide-co-glycolide-co-polyethyleneglycol-co-polyDL-lactide-co-glycolide-co-polyhistidine (PHis-b-PLGA-b-PEG-b-PLGA-b-PHis). The critical micelle concentrations (CMC) of the copolymers were measured with Pyrene Fluorescent Probe Technique. The temperature- and pH- sensitive properties of the blank micelles solution were investigated by optical transmittance measurement. The morphology and diameter of DOX micelles were characterized by transmission electron microscopy (TEM) and dynamic light scattering (DLS). The entrapment rate and drug-loading rate were determined with dialysis method. The in vitro release study was further performed to examine the temperature- and pH-responsive drug release behavior from DOX-loaded micelles. The results indicated that the CMC, entrapment efficiency and drug-loaded amount of the micelles were 7.5 x 10(-3) g x L(-1), 85.2 +/- 3.1% and 10.4 +/- 4.5%, respectively. The DOX micelle was globular-shaped with a mean diameter of 91.1 +/- 15.8 nm. The transmittance of micelle solution consistently increased with the increasing temperature or decreasing pH. In comparison to the drug release profile at physiological conditions (37 degrees C, pH 7.4), the DOX-loaded micelles showed faster drug release rate at higher temperature (41 degrees C), lower pH (pH 7.0, pH 6.5, pH 5.0) or higher temperature and lower pH (41 degrees C, pH 5.0). This indicated that the micelles showed a temperature and pH-triggered drug release pattern. Base on the above results, it can be concluded that PHis-b-PLGA-b-PEG-b-PLGA-b-PHis block copolymer micelles which respond to temperature and pH stimuli are promising smart carriers for anti-tumor drugs with the advantages of temperature- and pH- triggered drug release.

Preparation of adriamycin-loaded temperature/pH sensitive self-assembly block copolymer micelles / 药学学报

The dialysis method was employed to load adriamycin into the micelles formed by temperature and pH sensitive polyhistidine-co-DL-lactide-co-glycolide-polyethylene glycol poly DL-lactide-co-glycolide-co-histidine (OLH-b-PLGA-b-PEG-b-PLGA-b-OLH). The critical micelle concentration (CMC) of the copolymer was measured with pyrene fluorescent probe method under different temperatures. The entrapment rate and drug-loading rate were determined with dialysis method. The diameter, morphology and surface potential of the copolymer micelles were investigated by corresponding instruments, respectively. The release behavior of adriamycin from copolymer micelles and the pH sensitivity were studied. The CMC of the copolymers ranged from 0.022 4 to 0.001 7 microg x mL(-1). The entrapment rate and drug-loading rate were 92.8% and 15.7%, respectively. The micelles have a mean diameter of (61.7 +/- 13.4) nm, and zeta potential was -9.88 mV. The in vitro adriamycin release rate increased with the pH dropping from 7.4 to 5.0. The results indicated that the CMC of the copolymers decreased as the raising of temperature, drug release behavior from the micelles possessed clearly pH sensitivity, and the copolymers may have a potential in targeted delivery system for anticancer drugs.

Progress in the study of pH and temperature sensitive biodegradable block copolymers / 药学学报

pH and temperature sensitive biodegradable block copolymers are some macromolecules connected by biodegradable materials and pH sensitive monomers according to a certain sequence, or biodegradable polyesters polymerized themselves. On the basis of pertinent documents, the development of pH and temperature sensitive biodegradable block copolymers was introduced, involving their mechanism of action and potential application. PH and temperature sensitive biodegradable block copolymers could control the drug release rate freely, avoiding burst effect. Besides, the biocompatibility of these biodegradable materials is also excellent. So the use of pH and temperature sensitive biodegradable block copolymers as biodegradable drug delivery devices has attracted considerable interest in the intelligent drug delivery system.

Preparation and study in vitro of long-circulating nanoliposomes of curcumin / 中国中药杂志

<p><b>OBJECTIVE</b>To prepare the long-circulating nanoliposomes of curcumin.</p><p><b>METHOD</b>The long-circulating nanoliposomes were prepared by ethanol infusion and the encapsulation efficiency was determindated by the mini-column centrifugation. The effect of some factors on the encapsulation efficiency, such as the buffer solutions, the weight ratio of curcumin to SPC, the weight ratio of SPC to Chol, the pH of buffer solution and the iron strength of water phase, was investigated respectively. Then the formulation was optimized by orthogonal design.</p><p><b>RESULT</b>The encapsulation efficiency of the curcumin liposomes was (88.27 +/- 2.16)%, and the average diameter of the liposomes was (136 +/- 18) nm. There was no change on encapsulation efficency within 30 d.</p><p><b>CONCLUSION</b>The preparation of curcumin liposomes was easy and practicable and the pharmaceutical characterization showed that the curcumin liposomes are stable.</p>

Preparation of docetaxel-loaded pH-sensitive block copolymer micelles / 药学学报

Basing on the synthesis of pH-sensitive amphiphilic block copolymer poly (2-ethyl-2-oxazoline)-poly (D, L-lactide)(PEOz-PDLLA), this paper presents the preparation of docetaxel-loaded pH-sensitive block copolymer micelles using film dispersion method. The critical micelle concentration (CMC) was measured by pyrene fluorescent probe technique. The entrapment efficiency and drug-loaded amount were determined by HPLC. The morphology, diameter and surface potential of the micelles were characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS) and zeta potential analyzer, respectively. The in vitro release behavior of DTX from polymeric micelles was investigated using dialysis method. The results indicated that the CMC, drug-loaded amount and entrapment efficiency of the micelles was 1.0 x 10(-3) g x L(-1), 15.0% and 91.1%, respectively. The micelles had a narrow size distribution, with a mean diameter of 28.7 nm. The micelle was globular-shaped and its zeta potential was (1.19 +/- 0.12) mV. In pH 7.4 PBS, docetaxel was released in a sustained manner from the micelles; while in PBS at pH 5.0, drug was released more rapidly, which suggested the pH-sensitive drug release behavior of the PEOz-PDLLA micelles. According to all the studies above, it can be concluded that the PEOz-PDLLA block copolymer micelles may be applied as promising drug delivery system for hydrophobic anti-tumor drugs.

Preparation of lectin-conjugated PLGA nanoparticles and evaluation of their in vitro bioadhesive activity / 药学学报

In this study, wheat germ agglutinin (WGA), tomato lectin (TL) and asparagus pea lectin (AL) were covalently coupled to conventional poly lactic-co-glycolic acid (PLGA) nanoparticles using a carbodiimide method to take the bioadhesive properties. The influences of the amounts of activating agents and lectins, as well as the activating time and incubating time on the effect of lectin conjugating were investigated to optimize the preparation conditions. The mean diameters of the performed nanoparticles with or without lectin conjugation ranged from (140.7 +/- 5.7) nm to (245.6 +/- 18.3) nm. The yields of lectin conjugating and the lectin surface concentrations on nanoparticles were determined by Lowry's methods, and were calculated to be (18.97 +/- 2.9)% - (20.15 +/- 2.4)% and (9.46 +/- 1.45)--(10.05 +/- 1.19) microg x mg(-1), respectively. The in vitro bioadhesive activities of nanoparticles were evaluated by pig gastric mucin (PM) binding experiments. After incubation at room temperature for 60 min, the equilibria of binding between nanoparticles and PM reached. The percentages of the bulk PM which had interacted with different lectin-conjugated PLGA nanoparticles were 15.5%, 12.1% and 11.8%, respectively. The conjugation of lectin enhanced the interaction about 2.4 - 3.2 fold compared with that of the non-conjugated one. A mathematical model was used based on the Langmuir equation, and the rate constants of interaction (k) were calculated to be 2.373 x 10(-3), 1.536 x 10(-3) and 1.714 x 10(-3) (microg x min/mL)(-1), respectively. These interactions could be competitively inhibited by their corresponding sugars of lectins. The results suggested that lectin-conjugated PLGA nanoparticles greatly promoted the interaction with PM in vitro compared with the conventional PLGA nanoparticles, thus would improve the bioadhesion on gastrointestinal mucosa after oral administration resulting in a prolonged residence time in the gastrointestinal tract.

Recent advances in the study of dendrimers-based drug delivery systems / 药学学报

Dendrimers are hyperbranched, monodisperse and three dimensional macromolecules, which consist of an apolar core and polar shell have been referred to as "unimolecular micelles". This paper briefly describes the development and structural characteristics of dendrimers and also explains the feature of dendrimers as drug carrier and the dendrimer-drug interactions in details. Recently, dendrimers, which have attracted increasing attention for their applications in many fields such as drug targeted delivery systems and gene transfection, are becoming potential novel carriers.

Preparation and anti-oxidative activity of liposomal ferulic acid / 药学学报

Ferulic acid (FA) was loaded into liposomes via calcium acetate gradient with (80.2 +/- 5.2)% entrapment efficiency. The average sizes of blank liposome and FA liposome were about 155 nm and 154 nm, respectively. The zeta potential of blank liposome and FA liposome were (13.14 +/- 1.67) mV and (4.12 +/- 0.05) mV, respectively. Unilamellar vesicles were present in freeze-fracture electron microscopy. In the pharmacodynamic studies, the protective effect of liposomal ferulic acid on tBHP-challenged U937 cells was measured with the morphology of cell injury, mitochondrial transmembrane potential alternation and cell viability assay used as index. The results of MTT assay, microscopy indicated that FA liposomes exhibited greater antioxidant activity than FA solution on U937 cell.

Preparation and in vitro tumor cells selectivity of sterically stabilized immunoliposomal peptides in bee venom / 药学学报

Recently the use of peptides in bee venom (PBV) for cancer therapy has attracted considerable attention. In this study, the sterically stabilized liposomal PBV (PBV-SL) was prepared using soybean phosphatidylcholine, cholesterol, and cholesterol-PEG-COOH. The humanized antihepatoma disulfide-stabilized Fv (hdscFv25) was coupled to sterically stabilized liposomes using the N-hydroxysuccinimide ester method. The hdscFv25-immunoliposomes (SIL[hdscFv25]) were immunoreactive as determined by ELISA assay. SIL[hdscFv25] showed higher tumor cells selectivity. PBV-SIL[hdscFv25] can kill SMMC-7721 cells in vitro with higher efficiency than non-targeted liposomes. Whereas cytotoxicties were compared for Hela cells, no significant differences was observed between PBV-SIL[hdscFv25] and PBV-SL. Sterically stabilized immunoliposomal peptides in bee venom could be one drug targeting delivery system.