Ginsenoside Rg_3, an active component of traditional Chinese medicine(TCM), was used as the substitute for cholesterol as the membrane material to prepare the ginsenoside Rg_3-based liposomes loaded with dihydroartemisinin and paclitaxel. The effect of the prepared drug-loading liposomes on triple-negative breast cancer in vitro was evaluated. Liposomes were prepared with the thin film hydration method, and the preparation process was optimized by single factor experiments. The physicochemical properties(e.g., particle size, Zeta potential, and stability) of the liposomes were characterized. The release behaviors of drugs in different media(pH 5.0 and pH 7.4) were evaluated. The antitumor activities of the liposomes were determined by CCK-8 on MDA-MB-231 and 4T1 cells. The cell scratch test was carried out to evaluate the effect of the liposomes on the migration of MDA-MB-231 and 4T1 cells. Further, the targeting ability of liposomes and the mechanism of lysosome escape were investigated. Finally, H9c2 cells were used to evaluate the potential cardiotoxicity of the preparation. The liposomes prepared were spheroid, with uniform particle size distribution, the ave-rage particle size of(107.81±0.01) nm, and the Zeta potential of(2.78±0.66) mV. The encapsulation efficiency of dihydroartemisinin and paclitaxel was 57.76%±1.38% and 99.66%±0.07%, respectively, and the total drug loading was 4.46%±0.71%. The accumulated release of dihydroartemisinin and paclitaxel from the liposomes at pH 5.0 was better than that at pH 7.4, and the liposomes could be stored at low temperature for seven days with good stability. Twenty-four hours after administration, the inhibition rates of the ginsenoside Rg_3-based liposomes loaded with dihydroartemisinin(70 μmol·L~(-1)) and paclitaxel on MDA-MB-231 and 4T1 cells were higher than those of the positive control(adriamycin) and free drugs(P<0.01). Compared with free drugs, liposomes inhibited the migration of MDA-MB-231 and 4T1 cells(P<0.05). Liposomes demonstrated active targeting and lysosome escape. In particular, liposomes showed lower toxicity to H9c2 cells than free drugs(P<0.05), which indicated that the preparation had the potential to reduce cardiotoxicity. The findings prove that ginsenoside Rg_3 characterized by the combination of drug and excipient is an ideal substitute for lipids in liposomes and promoted the development of innovative TCM drugs for treating cancer.
Humans ; Paclitaxel/pharmacology* ; Liposomes/chemistry* ; Ginsenosides/therapeutic use* ; Triple Negative Breast Neoplasms/drug therapy* ; Cardiotoxicity/drug therapy* ; Cell Line, Tumor

Currently, the first-line drugs for invasive fungal infections (IFI), such as amphotericin B, fluconazole and itraconazole, have drawbacks including poor water solubility, low bioavailability, and severe side effects. Using drug delivery systems is a promising strategy to improve the efficacy and safety of traditional antifungal therapy. Synthetic and biomimetic carriers have greatly facilitated the development of targeted delivery systems for antifungal drugs. Synthetic carrier drug delivery systems, such as liposomes, nanoparticles, polymer micelles, and microspheres, can improve the physicochemical properties of antifungal drugs, prolong their circulation time, enhance targeting capabilities, and reduce toxic side effects. Cell membrane biomimetic drug delivery systems, such as macrophage or red blood cell membrane-coated drug delivery systems, retain the membrane structure of somatic cells and confer various biological functions and specific targeting abilities to the loaded antifungal drugs, exhibiting better biocompatibility and lower toxicity. This article reviews the development of antifungal drug delivery systems and their application in the treatment of IFI, and also discusses the prospects of novel biomimetic carriers in antifungal drug delivery.
Antifungal Agents/therapeutic use* ; Drug Delivery Systems ; Amphotericin B/therapeutic use* ; Liposomes/chemistry* ; Nanoparticles ; Drug Carriers

BACKGROUND: Afatinib, a second-generation irreversible epidermal growth factor inhibitor receptor for the development of non-small cell lung cancer and secondary drug resistance, has low bioavailability and adverse reactions due to current oral administration. The aim of this study was to prepare a novel drug delivery system, afatinib liposome, and to establish a method for the determination of encapsulation efficiency. METHODS: Four different preparation methods were used to prepare afatinib liposomes, and the optimal preparation process was determined by comparing the encapsulation efficiency and particle size. RESULTS: It has been verified that sephadex microcolumn centrifugation can be used to purify afatinib liposomes, and UV spectrophotometry can be employed to determine the entrapment efficiency of liposomes. Among different preparation methods, the encapsulation efficiency of afatinib liposomes prepared by ammonium sulfate gradient method was 90.73% and the average particle size was 108.6 nm. CONCLUSIONS Ammonium sulfate gradient method can be successfully applied to prepare afatinib liposomes that performed higher encapsulation efficiency and smaller particle size. The UV spectrophotometry employed to determine the liposome encapsulation efficiency was easy operation and with high accuracy.
Afatinib ; Capsules ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; Drug Compounding ; methods ; Liposomes ; Lung Neoplasms ; drug therapy ; Quinazolines ; administration & dosage ; chemistry ; therapeutic use

In this study, the buffering capacity of amphiphilic pH-sensitivity copolymer poly(2-ethyl-2-oxazoline)-cholesteryl methyl carbonate (PEOZ-CHMC) was evaluated. The ammonium sulfate gradient method was used to prepare doxorubicin hydrochloride (DOX x HCl)-loaded liposomes (DOX-L), and then the post-insertion method was used to prepare PEOZ-CHMC and polyethylene glycol-distearoyl phosphatidyl ethanolamine (PEG-DSPE) modified DOX x HCl-loaded liposomes (PEOZ-DOX-L and PEG-DOX-L). The physico-chemical properties, in vitro drugs release behavior, cellular toxicity and intracellular delivery of liposomes were evaluated, separately. The results showed that PEOZ-CHMC has a satisfactory buffering capacity. The sephadex G-50 column centrifugation method and dynamic light scattering were used to determine the encapsulation efficiency (EE) and particle size of liposomes. The EE and particle size of DOX-L were (97.3 ± 1.4) % and 120 nm, respectively, and the addition of PEOZ-CHMC or PEG-DSPE had no influence on EE and particle size. The zeta potentials of three kinds of liposomes were negative. The release behavior of various DOX liposomes in vitro was investigated by dialysis method. In phosphate buffer solution (PBS) at pH 7.4, DOX x HCl was released from PEOZ-DOX-L in a sustained manner. While in PBS at pH 5.0, the release rate of DOX x HCl from PEOZ-DOX-L increased significantly, which suggested DOX x HCl was released from PEOZ-DOX-L in a pH-dependent manner. The intracellular delivery of liposomes was investigated by confocal laser scanning microscopy (CLSM). The CLSM images indicated that PEOZ-DOX-L showed efficient intracellular trafficking including endosomal escape and release DOX x HCl into nucleus, as well as the DOX-L and PEG-DOX-L had no this effect. The cytotoxicity of liposomes against MCF-7 cells was detected by using MTT assay. The results showed that antiproliferative effects of PEOZ-DOX-L enhanced with pH value decreased, whereas DOX-L and PEG-DOX-L did not have any significant difference in inhibitions at different pH conditions. Therefore, the problems of the inhibition of cellular uptake of liposomes and the failed endosomal escape of pH-sensitive liposomes by PEG chain can be overcome by the pH-sensitive liposomes constructed by PEOZ-CHMC.
Cell Nucleus ; Doxorubicin ; analogs & derivatives ; chemistry ; Endosomes ; Formates ; chemistry ; Humans ; Liposomes ; chemistry ; MCF-7 Cells ; Microscopy, Confocal ; Particle Size ; Phosphatidylethanolamines ; Polyamines ; chemistry ; Polyethylene Glycols ; chemistry

The purpose of the study is to construct R8 peptide (RRRRRRRR) and pH sensitive polyethylene glycols (PEG) co-modified liposomes (Cl-Lip) and utilize them in breast cancer treatment. The co-modified liposomes were prepared with soybean phospholipid, cholesterol, DSPE-PEG2K-R8 and PEG5K-Hz-PE (pH sensitive PEG). The size and zeta potential of Cl-Lip were also characterized. The in vitro experiment demonstrated that the Cl-Lip had high serum stability in 50% fetal bovine serum. The cellular uptake of Cl-Lip under different pre-incubated conditions was evaluated on 4T1 cells. And the endocytosis pathway, lysosome escape ability and tumor spheroid penetration ability were also evaluated. The results showed the particle size of the Cl-Lip was (110.4 ± 5.2) nm, PDI of the Cl-Lip was 0.207 ± 0.039 and zeta potential of the Cl-Lip was (-3.46 ± 0.05) mV. The cellular uptake of Cl-Lip on 4T1 cells was pH sensitive, as the cellular uptake of Cl-Lip pre-incubated in pH 6.0 was higher than that of pH 7.4 under each time point. The main endocytosis pathways of Cl-Lip under pH 6.0 were micropinocytosis and energy-dependent pathway. At the same time, the Cl-Lip with pre-incubation in pH 6.0 had high lysosome escape ability and high tumor spheroid penetration ability. All the above results demonstrated that the Cl-Lip we constructed had high pH sensitivity and is a promising drug delivery system.
Animals ; Cell Line, Tumor ; Cell-Penetrating Peptides ; chemical synthesis ; chemistry ; Cholesterol ; chemistry ; Drug Delivery Systems ; Liposomes ; Mice ; Oligopeptides ; chemical synthesis ; chemistry ; Particle Size ; Phospholipids ; chemistry ; Polyethylene Glycols

Polyethylene glycol (PEG) is extensively used to increasing the in vivo and in vitro stability of liposomes. However, PEGylated liposomes also produce some negative effects with further research, such as low cellular uptake, poor "endosomal escape" of pH sensitive liposome (PSL) and accelerated blood clearance (ABC) phenomenon, and this situation is referred as the "PEG dilemma". "PEG dilemma" posed severe challenges for the targeted delivery of PEGylated liposomes-loaded anticancer drugs, effective intracellular release of PEGylated PSL-encapsulated gene and protein drugs, and repeated administration of PEGylated liposomes. Therefore, it is urgent to solve the "PEG dilemma". This review focused on the definition, classification of "PEG dilemma", and discussed several possible approaches to overcome "PEG dilemma".
Antineoplastic Agents ; chemistry ; Drug Carriers ; chemistry ; Liposomes ; chemistry ; Polyethylene Glycols ; chemistry

OBJECTIVETo characterize the property of uricase loaded in uricase-catalase liposomes (BUCLPs) prepared using borate buffer.

METHODSBUCLPs were prepared using reverse-phase evaporation, and the physicochemical properties of uricase in the prepared BUCLPs were examined.

RESULTSThe optimal temperature of BUCLP and URI was 40 degrees celsius, their optimal pH values were 8.0 and 8.5, and their Michaelis-Menten constants were 14.207 µmol/L and 13.623 µmol/L, respectively. Fluorescence intensity of nanoliposome-loaded uricase-catalase that bound to FITC was higher than that of uricase-catalase binding directly with FITC; the fluorescence intensity of BUCLP was higher than that of free uricase-catalase at 280 nm.

CONCLUSIONUricase activity is enhanced after loading in uricase and catalase liposomes.

The purpose of this study is to explore the feasibility of wheat germ agglutinin (WGA) modified liposome as a vehicle for ophthalmic administration. Liposome loaded with 5-carboxyfluorescein (FAM) was prepared by lipid film hydration method. WGA was thiolated and then conjugated to the surface of the liposome via polyethylene glycol linker to constitute the WGA-modified and FAM-loaded liposome (WGA-LS/FAM). The amount of thiol groups on each WGA molecule was determined, and the bioactivity of WGA was estimated after it was modified to the surface of liposome. The physical and chemical features of the WGA-modified liposome were characterized and the ocular bioadhesive performance was evaluated in rats. The result showed that each thiolated WGA molecule was conjugated with 1.32 thiol groups. WGA-LS/FAM had a mean size of (97.40 +/- 1.39) nm, with a polydispersity index of 0.23 +/- 0.01. The entrapment efficacy of FAM was about (2.95 +/- 0.21)%, and only 4% of FAM leaked out of the liposome in 24 h. Erythrocyte agglutination test indicated that after modification WGA preserved the binding activity to glycoprotein. The in vivo ocular elimination of WGA-LS/FAM fitted first-order kinetics, and the elimination rate was significantly slower than that of the unmodified liposome, demonstrating WGA-modified liposome is bioadhesive and suitable for ophthalmic administration.
Absorption, Physicochemical ; Adhesiveness ; Administration, Ophthalmic ; Animals ; Drug Carriers ; Eye ; metabolism ; Fluoresceins ; chemistry ; Liposomes ; administration & dosage ; chemistry ; pharmacokinetics ; Male ; Particle Size ; Polyethylene Glycols ; chemistry ; Rats ; Rats, Sprague-Dawley ; Wheat Germ Agglutinins ; administration & dosage ; chemistry ; pharmacokinetics

In this study, the herpetin (HPT) lyophilized liposome was prepared, and its saftey and pharmacodynamics were evaluated. HPT lyophilized liposome was prepared by thin-film ultrasonication method. The lyoprotectant was optimized using particle size and encapsulation efficiency as indexes. Then, the influencing factors of HPT lyophilized liposome were investigated. In addition, preliminary safety and therapy efficiency of HPT lyophilized liposome to liver injury induced by CCl4 in the mice. The optimal lyoprotectant was 5% sucrose plus 5% lactose and the dispersed HPT lyophilized liposomes were spherical with the mean diameter of (107.0 ± 1.2) nm and the mean encapsulation efficiency of (99.7 ± 0.50)%. The lyophilized powder was sensitive to temperature, humidity and illumination. None of hemolysis, hemagglutination and vein irritation was observed after intravenous injection of HPT lyophilized liposomes into rabbits. HPT lyophilized liposome showed obviously therapy efficiency to liver injury induced by CCl4 in the mice. The improvements of ALT, AST and ALP were better than that in HPT free drug. The obtained HPT lyophilized liposome met the standard of CP with fine particle size and encapsulation efficiency after dispersion. The HPT lyophilized liposome showed good safety and enhanced the treatment efficacy of HPT. The HPT lyophilized liposome should be stored in low temperature, sealed condition far away from light.
Animals ; Chemistry, Pharmaceutical ; Cucurbitaceae ; chemistry ; Drug Carriers ; chemistry ; Drug Evaluation, Preclinical ; Drug Stability ; Drugs, Chinese Herbal ; adverse effects ; chemistry ; pharmacokinetics ; Liposomes ; chemistry ; Male ; Mice ; Mice, Inbred ICR ; Rabbits

In this study, we developed a novel liposome-silica hybrid nano-carrier for tumor combination therapy via oral route, using paclitaxel and cyclosporine as a model drug pair. Optimization of the preparation of the drug-loading formulation and characterization of its physicochemical parameters and drug release profile were performed in vitro. Then in vivo pharmacodynamics and pharmacokinetics studies were performed. The results showed that the obtained formulation has a small particle size (mean diameter of 100.2 +/- 15.2 nm), a homogeneous distribution [the polydispersity index was (0.251 +/- 0.018)] and high encapsulation efficiency (90.15 +/- 2.47) % and (80.64 +/- 3.52) % for paclitaxel and cyclosporine respectively with a mild and easy preparation process. A sequential drug release trend of cyclosporine prior to palictaxel was observed. The liposome-silica hybrid nano-carrier showed good biocompatibility in vivo and co-delivery of cyclosporine and paclitaxel significantly enhanced the oral absorption of paclitaxel with improved anti-tumor efficacy, suggesting a promising approach for multi-drug therapy against tumor and other serious diseases via oral route.
ATP-Binding Cassette, Sub-Family B, Member 1 ; antagonists & inhibitors ; Administration, Oral ; Animals ; Antineoplastic Agents, Phytogenic ; administration & dosage ; pharmacokinetics ; pharmacology ; Biological Availability ; Cyclosporine ; administration & dosage ; pharmacokinetics ; pharmacology ; Drug Carriers ; chemistry ; Female ; Liposomes ; chemistry ; Male ; Mice ; Nanoparticles ; Neoplasm Transplantation ; Paclitaxel ; administration & dosage ; pharmacokinetics ; pharmacology ; Particle Size ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Sarcoma 180 ; pathology ; Silicon Dioxide ; chemistry ; Tumor Burden ; drug effects