Tumor microenvironment responsive liposomes blocking CXCL12/CXCR4 pathway and synergistically enhancing immune efficacy of anti-PD-L1 / 药学学报

Blocking immune checkpoint programmed cell death receptor 1 (PD-1) or programmed death receptor-ligand 1 (PD-L1) can enhance anti-tumor activity of effector T cells. However, the lack of response in many patients to PD-1/PD-L1 therapy remains a question. Improving the immunosuppressive tumor microenvironment (TME) to enhance the efficacy of immune checkpoint inhibitors has become a promising cancer treatment strategy. We constructed a liposome system (PD-L1/siCXCL12-Lp) of CXCL12 siRNA and anti-PD-L1 peptide with matrix metalloproteinases (MMPs) responsiveness, which combined the TME regulation of siCXCL12 and the immune regulation of anti-PD-L1 peptide. All animal experiments were approved by the Biomedical Ethics Committee of Peking University. The authors found that PD-L1/siCXCL12-Lp directly down-regulated the expression of CXCL12 in vitro (33.8%) and in vivo (15.5%). It also effectively increased the ratio of CD8+/Treg by 20.0%, which helped the anti-PD-L1 peptide to better exert its immune effect. The combination therapy significantly inhibited tumor growth (52.08%) with great safety, which explored a new idea for cancer immunotherapy.

Interfacial properties and micellization of triblock poly(ethylene glycol)-poly(-caprolactone)-polyethyleneimine copolymers

This study aimed to explore the link between block copolymers' interfacial properties and nanoscale carrier formation and found out the influence of length ratio on these characters to optimize drug delivery system. A library of diblock copolymers of PEG-PCL and triblock copolymers with additional PEI (PEG-PCL-PEI) were synthesized. Subsequently, a systematic isothermal investigation was performed to explore molecular arrangements of copolymers at air/water interface. Then, structural properties and drug encapsulation in self-assembly were investigated with DLS, SLS and TEM. We found the additional hydrogen bond in the PEG-PCL-PEI contributes to film stability upon the hydrophobic interaction compared with PEG-PCL. PEG-PCL-PEI assemble into smaller micelle-like (such as PEG-PCL4006-PEI) or particle-like structure (such as PEG-PCL8636-PEI) determined by their hydrophilic and hydrophobic block ratio. The distinct structural architectures of copolymer are consistent between interface and self-assembly. Despite the disparity of constituent ratio, we discovered the arrangement of both chains guarantees balanced hydrophilic-hydrophobic ratio in self-assembly to form stable construction. Meanwhile, the structural differences were found to have significant influence on model drugs incorporation including docetaxel and siRNA. Taken together, these findings indicate the correlation between molecular arrangement and self-assembly and inspire us to tune block compositions to achieve desired nanostructure and drug loading.

Preparation and characterization of paclitaxel microspheres in situ gel and its antitumor efficacy by local injection / 北京大学学报(医学版)

OBJECTIVE@#The current difficulties in the treatment of tumor include repeated administration and high recurrence rate after tumor resection. In order to reduce the number of doses, avoid side effects of chemotherapeutic drugs, suppress tumor growth and delay tumor recurrence after surgery, a temperature-sensitive in situ gel with paclitaxel microspheres (PTX/M gel) was prepared. PTX/M gel was administered by intratumoral injection once a month.@*METHODS@#First of all, paclitaxel microspheres (PTX/M) were prepared by emulsion solvent evaporation method. A laser particle size distribution analyzer was used to investigate the size, distribution, specific surface area of microspheres. Paclitaxel content was determined by high performance liquid chromatography (HPLC). Then encapsulation efficiency of paclitaxel was calculated and in vitro release characteristics were studied. Secondly, PTX/M gel was prepared by cold dissolution method. The phase transition temperature, elastic modulus, dissolution curve, correlation between dissolution and release were measured. Finally, U87 MG and 4T1 subcutaneous tumor models were established respectively to study the efficacy of PTX/M gel in suppressing tumor growth and delaying tumor recurrence after surgery.@*RESULTS@#The median diameter of the selected PTX/M was (32.24±1.09) μm, the specific surface area was (206.61±10.23) m2/kg, the encapsulation efficiency was 85.29%±1.34%, and the cumulative release percentage of paclitaxel from PTX/M was 33.56%±3.33% in one month. Phase transition temperature of PTX/M gel was 33 °C. The elastic modulus of PTX/M gel at 25 °C and 37 °C were 4.2×103 Pa and 18×103 Pa, respectively. The gel could stay in the body for up to 48 hours. It could be seen from the results of animal experiments that were compared with the saline group and the Taxol group, and the tumor-bearing mice of the PTX/M gel group had the slowest tumor growth (P<0.05). Similarly, in the tumor recurrence experiments, the mice of PTX/M gel group had the latest tumor recurrence after surgery.@*CONCLUSION@#As a local sustained-release preparation, PTX/M gel can effectively suppress tumor growth and delay postoperative recurrence of tumors. It has potential advantages in tumor treatment.

Research situation of pH low insertion peptides / 药学学报

Extracellular acidity has been associated with many pathological states, such as cancer, ischemic stroke, neurotrauma and infection, which makes it an effective target for therapy and diagnosis of such diseases. As a polypeptide vector, pH low insertion peptides (pHLIPs) are endowed with high sensitivity to extracellular acidic environment, which can insert the membrane and deliver payload to pathological cells in a pH dependent manner. Here, theranostic applications of pHLIP in disease, are reviewed in two aspects:pHLIP-mediated single-molecule transporter and nano-sized carrier.

Activatable cell-penetrating peptides: a potential activatable modality for diseases diagnosis and therapy / 药学学报

Cell-penetrating peptides are composed of positively-charged amino acids that can mediate molecules or nano-carriers across cell membranes. However, most of the known cell-penetrating peptides have no cell-or tissue-specificity, with affinity to almost all types of cells in internalization. The non-specificity of cell-penetrating peptides is a significant obstacle in the application to targeted delivery of imaging probes and therapeutic agents. Accordingly, many studies focused on selective switching of systemically-delivered inert cell-penetrating peptides into active forms in diseased tissues. Tsien groups introduced the concept of activatable cell-penetrating peptides in 2004. Subsequently, a growing number of similar delivery systems (molecular or nano-sized) have been documented, and the sensitive factors have included enzyme, lower pH, light and exogenous component. In this paper, we make an overview of the development of activatable delivery system in recent years.

Rules and characteristics of crystallization inhibition of cellulose polymers against drugs in supersaturated states / 药学学报

This study aims to explore the characteristics of crystallization inhibition by cellulose polymers at the supersaturated states of drugs. The study was performed by simulating supersaturated process and preparing supersaturated drug solid, and was carried out by measuring the content of drugs at different time points using dissolution apparatus. The types, amounts, ionic intensity and viscosity of cellulose polymers were examined to assess the crystallization inhibition effect on BCS II class drug indomethacin. HPMC E15 exhibited the strongest crystallization inhibition effect. The more added, more obvious crystallization suppression was observed against indomethacin. The decrease in viscosity and increase in ionic intensity led to an enhanced inhibition. The research provides a scientific guide for the crystallization inhibition of supersaturated drug by cellulose polymers.

The application of enzyme-sensitive activatable cell-penetrating peptides to targeted delivery system / 药学学报

Cell-penetrating peptides (CPPs) offer a non-selective and receptor-independent mode to promote cellular uptake. Although the non-specificity of CPP-mediated internalization allows this approach applicable to a wide range of tumor types potentially, their universality is a significant obstacle to their clinical utility for targeted delivery of cancer therapeutics and imaging agents. Accordingly, many reports have focused on selective switching of systemically delivered inert CPPs into their active form in lesions (tumor). In this review, our attention is mainly confined to such an enzyme-sensitive domain incorporated delivery system with activatable CPPs (ACPPs), which have displayed the exciting strength in balancing the CPPs' pros and cons, and potential in the treatment and diagnosis of some diseases.

Preparation of rivastigmine liposome and its pharmacokinetics in rats after intranasal administration / 药学学报

To prepare rivastigmine liposome, rivastigmine was loaded into liposome via ammonium sulfate gradient method. Its pharmacokinetic profile in rats was evaluated after intranasal administration. The size, zeta potential, entrapped efficiency and release of rivastigmine from the liposome in vitro were determined. Plasma concentration of rivastigmine was determined by high performance liquid chromatography-tandem mass spectrometry (HPLC/MS) using antipyrine as internal standard. The pharmacokinetic parameters were calculated by DAS 2.0. The entrapped efficiency of rivastigmine liposome was (33.41 +/- 6.58) %, with the mean diameter of 154-236 nm and zeta potential of (-10.47 +/- 2.41) mV. The release behavior of rivastigmine was fitting the first order equation in vitro. The pharmacokinetic studies indicated that the C(max), T(max) and AUC(0-infinity), of rivastigmine liposome were (1.50 +/- 0.15) mg x L(-1), 15 min and (89.06 +/- 8.30) mg x L(-') x min, respectively. Rivastimine liposome was absorbed rapidly, and could reach a certain concentration in rat plasma after intranasal delivery.

Comparison of mechanisms and cellular uptake of cell-penetrating peptide on different cell lines / 药学学报

Cell-penetrating peptide (CPP) can be used in pharmaceutics as a highly efficient drug delivery transporter. In this study, four tumor cell lines (MCF-7, MDA-MB-231, C6, and B16F10) were used to observe the uptake of fluorescein isothiocyanate (FITC) labeled CPP and the effects of time and concentration of CPP on cell penetration was studied. The CPP exocytosis on C6 cell line was observed, and its exocytosis kinetics was described by zero order equation. In addition, low-temperature condition (4 degrees C) and endocytosis inhibitors were utilized to investigate the mechanism of CPP uptake by cells. Low-temperature condition did not show significantly inhibition on CPP uptake. Heparin, a membrane glycoprotein receptor inhibitor, showed strong inhibition effect (only 3%-10% of the control) on CPP uptake. Chlorpromazine, chloroquine and 5-(N-ethyl-N-isopropyl)-amiloride (EIPA) showed little effect on CPP uptake. This study indicated that CPP penetration had little selectivity on cell type, but the amount and rate of CPP penetration into cells were related to the type of cell lines. The adsorption of CPP on cell membrane induced by sulfate proteoglycan plays an important role on CPP penetration.

The design and enzymatic hydrolysis of activatable cell-penetrating peptide / 药学学报

The paper is aimed to study the enzymatic hydrolysis of the activatable cell-penetrating peptide (ACPP) that was designed and synthesized. The ACPP was composed of three parts, polyanionic sequence peptide, peptide sequence that specifically cleaved by matrix metalloproteinase (MMP) and cell penetrating peptide (CPP). The ACPP was hydrolyzed by type IV collagenase (MMP-2/9) under the condition of 37 degrees C and was monitored by reversed-phase high performance liquid chromatography (RP-HPLC). The efflux of peak was collected and detected by matrix assisted laser desorption ionization orthogonal time of flight mass spectrometry (MALDIO-TOF-MS) to speculate the sequences of the peptide fragments. The results indicated that the ACPP could be cleaved by type IV collagenase at target site as predicted, released CPP. The half life of the cleavage was about 4 h. Meanwhile, the peptide fragments may be cleaved again at other sites by type IV collagenase.

Preparation and properties of folate receptor-targeted cationic liposomes / 药学学报

A cationic liposome was prepared with a ligand directed at folate receptor in cancer cells to improve selectivity and facilitate its access to the cancer cells. Folate-polyethyleneglycol-distearoylphosphatidylethanolamine (F-PEG-DSPE) was synthesized by reacting folic acid (F), polyoxyethylene-bis-amine (NH2-PEG-NH2), succinic anhydride (SUC) with distearoylphosphatidylethanolamine (DSPE). Folate receptor-targeted liposomes composed of DPPC/DC-Chol/F-PEG-DSPE (10:10:0.75, molar ratio) were prepared by film dispersion method. A negative charged dextran fluorescein anionic (DFA) was used as a model to explore the in vitro properties and cell uptake efficiencies of liposomal DFA on KB and HpeG2 cells. The formulations were investigated by orthogonal experiment using encapsulation efficiency as the optimized indexes. The size, 4 potential, entrapment efficiency and DFA release in vitro were investigated. The results showed that DFA loaded folate receptor-targeted liposomes had high encapsulation efficiency and the mean size approximately 144 nm. The cationic liposomes had some toxicity to HepG2 cells, and at low concentration (0.0125-0.1 micromol x L(-1)) , the toxicity was linear with the concentration of DC-chol. The folate receptor-targeted liposomes showed great effects on increasing liposome cellular uptake of DFA. In summary, the method of film dispersion method is suitable for producing DFA loaded lipsomes with high entrapment efficiency, small size and slow release. The folate receptor-targeted liposomes can efficiently deliver DFA into cells in vitro. This may represent a promising option for researches on cancer gene therapy.

Cationic liposomes loaded with doxorubicin targeting to the tumor neovasculature in vitro / 药学学报

This study was conducted to investigate the in vitro characteristics of cationic liposomes composed of 3beta-[N-[2-(N', N'-dimethylamino) ethyl] carbamoyl] cholesterol (DC-Chol) and dipalmitoylphosphatidylcholine loaded with doxorubicin (DXR), and to provide useful information for the in vivo tumor vascular targeting of cationic liposomes. Cationic liposomes composed of different amounts of DC-Chol (0 mol%, 10 mol%, 25 mol%, 50 mol%) were loaded with the conventional anti-cancer drug doxorubicin. Their size, zeta potential, encapsulation efficiency, and DXR release in vitro were investigated. Moreover, their uptake by rat aortic endothelial cells (RAECs) was observed at 15 min, 30 min, 1 h, and 4 h of incubation. FITC-Dextran was i.v. injected to the H22 tumor-bearing KM mice to stain the neovasculature. The characteristics of resulting DXR-loaded cationic liposomes were in stable characteristics with particle sizes around 100 - 200 nm and capsulation efficiency greater than 90%. Increased cationic lipid led to enhanced zeta potential, and meanwhile it also resulted in quick release of the loaded drug, indicating increased slits or pores on the membrane upon the addition of DC-Chol. RAECs could more avidly take up DXR-loaded cationic liposomes when the content of DC-Chol increased in the liposomes, and DXR were quickly released in the cytoplasm and transported to the nuclei. The neovasculature stained by FITC-Dextran was clearly observed. DXR-cationic liposomes composed of DC-Chol could be used for tumor vascular targeting in vivo for further study.

Immunogenicity of single-dose HBsAg-PLGA controlled release microspheres in mice / 药学学报

<p><b>AIM</b>To investigate the level of immune response and the immune mechanism of the single-dose hepatitis B surface antigen (HBsAg)-poly (d, l)-lactide-co-glicolide acid (PLGA) microspheres in BALB/c mice.</p><p><b>METHODS</b>Three kind of HBsAg-PLGA microspheres, HBsAg-PLGA50/50-COOH microspheres, HBsAg-PLGA75/25 microspheres and HBsAg-PLGA50/50 microspheres, were prepared by double emulsion microencapsulation technique used three kinds of PLGA with different L/G ratio. The single-dose of HBsAg-PLGA microspheres was subcutaneously injected into BALB/c mice at the dose of 7.5 microg HBsAg per mouse. The conventional aluminum-adjuvant vaccine was subcutaneously injected at 0, 1 and 2 month as positive control. In certain time interval, the induced immune level of total antibody was detected by enzyme linked immunosorbent assay (ELISA). For subclass of IgG antibody and cytokines studies, the dose of HBsAg was 2.5 microg per mouse.</p><p><b>RESULTS</b>The HBsAg-PLGA microspheres could successfully induce a humoral immune response in BALB/c mice. Compared with the conventional aluminum-adjuvant vaccine, the antibody response of the HBsAg-PLGA50/50-COOH microspheres was significantly lower than the group received three injections of aluminum-adjuvant vaccine (P < 0.01) except for a higher priming response during the early 6 weeks. The results were ascribed to the relatively rapid degradation charactics of PLGA50/50-COOH polymer. The immune response for the HBsAg-PLGA50/50 microspheres and HBsAg-PLGA75/25 microspheres were comparable to the group administered with aluminum-adjuvant vaccine (P > 0.05) which was due to the sustained degradation of PLGA50/50 and PLGA75/25 polymer.</p><p><b>CONCLUSION</b>The HBsAg-PLGA microsphere is a promising candidate for the controlled delivery of a vaccine which does not require multiple injections.</p>

Pharmacokinetics of doxorubicin alginate microspheres and evaluation of its hepatic arterial embolization in vivo / 药学学报

<p><b>AIM</b>To investigate the pharmacokinetics of doxorubicin alginate microspheres (DOX-AM) in vivo after hepatic arterial embolization.</p><p><b>METHODS</b>China miniature pigs were chosen as the experimental animals. Transcatheter hepatic arterial chemoembolization (TACE) with DOX-AM (experimental group), lipiodol and DOX (DOX-lipiodol, control group 1), and infusion with DOX (control group 2) were performed after angiography and superselection of an intrahepatic branch of hepatic artery. After chemoembolization or infusion, the blood was collected at different time intervals. Drug concentration in plasma was measured by HLPC and the parameters of pharmacokinetics were calculated.</p><p><b>RESULTS</b>The values of T1/2, AUC, Cmax, and MRT of the DOX-AM were significantly different from those of control group 1 and control group 2. After embolization, the DOX-AM embolized in the vessel and still retained there at 8 weeks. The digital subtraction arteriography (DSA) and computerized tomography (CT) showed the reliable embolization results. The histological examination indicated that the liver damnifications were changed transitorily in all groups (P < 0.05) and were recovered within two weeks. The liver damnifications increased in following order: DOX < DOX-AM < DOX-lipiodol.</p><p><b>CONCLUSION</b>DOX-AM showed definite property of delayed release of drug in liver, and increased the retention time and concentration of DOX after embolization in vivo.</p>

Transfection and anti-HBV effect mediated by the hepatocytes-targeting cationic liposomes co-modified with beta-sitosterol-beta-D-glucoside and Brij 35 / 药学学报

<p><b>AIM</b>To study the transfection and anti-hepatitis B virus (HBV) effect of the co-modified hepatocytes-targeting cationic liposomes encapsulating anti-HBV antisense oligonucleotides (asON) , and to investigate the transfection mechanisms of the liposomes.</p><p><b>METHODS</b>Dipalmitoylphosphatidylcholine (DPPC) and 3beta-[N-(N',N'-dimethylaminoethane)-carbamoyl] cholesterol (DC-Chol) were used as the lipids, beta-sitosterol-beta-D-glucoside (sito-G) and Brij 35 were used to modify the liposomes. Flow cytometry (FCM), fluorescence microscopy and enzyme-linked immunosorbent assay (ELISA) were utilized to evaluate the transfection improvement of the asON encapsulated in the liposomes in primary rat hepatocytes and the antigens inhibition activity in HepG 2.2.15 cells. The transfection mechanisms were evaluated based on the influence of wortmannin, nigericin, and asialofetuin on the antigens inhibition in HepG 2.2.15 cells by ELISA.</p><p><b>RESULTS</b>The co-modification with sito-G and Brij 35 significantly improved the transfection of the liposomes in primary rat hepatocytes and antigens inhibition effect in HepG 2.2.15 cells. Both transfection efficiency and antigens inhibition effect showed to be concentration-dependent with the asON-encapsulating liposomes. In fluorescence microscopy, the transfected cells showed strong fluorescence in primary rat hepatocytes, especially in the nuclei. Wortmannin, nigericin and asialofetuin decreased the antigens inhibition of the asON-encapsulating liposomes to different levels. Cationic liposomes modification with sito-G and Brij 35 could improve the transfection and antigens inhibition effect of the asON. The transfection mechanisms of the co-modified liposomes included endocytosis and membrane fusion. The ligand sito-G was confirmed to be able to enhance asialoglycoprotein receptor (ASGPR)-mediated endocytosis.</p><p><b>CONCLUSION</b>Co-modified hepatocytes-targeting cationic liposomes would be a specific and effective carrier to transfer asON into hepatocytes.</p>

Liver targeting of cationic liposomes modified with soybean-derived sterylglucoside in vitro / 药学学报

<p><b>AIM</b>To construct a liposomal liver targeting delivery system by adding soybean-derived sterylglucoside (SG) to the cationic liposomes.</p><p><b>METHODS</b>The physico-chemical properties of SG modified cationic lipsomes were investigated using fluorescein sodium (FS) as a model drug, as well as the interaction of SG modified liposomes with HepG2 2. 2. 15 cells in the point of involvement of asialoglycoprotein receptor (ASGP-R) mediated transfection. Liver targeting of modified cationic liposomes were also investigated using liver perfusing technique, and hepatocytes and non-hepatocytes were separated and examined after perfusing.</p><p><b>RESULTS</b>All the formula yielded high incorporation efficiency (83.12% - 91.74%), small particle size (93.0 - 124.4 nm). The zeta potential of blank liposomes all showed positive values. The transfection efficiency of FS entrapped in SG-liposomes with HepG2 2.2. 15 was significantly higher than that of liposomes without modification. The transfection of SG-liposomes were reduced significantly by the 20/30 mmol galactose as a competitor of ASGP-R. All the cationic liposomes showed high level of liver uptake of FS. Compared with the uptake of non-hepatocytes of each respectively, only SG/Brij-35 liposomes showed difference in FS uptake by hepatocytes (P < 0.05).</p><p><b>CONCLUSION</b>It showed that SG/Brij-35 modified cationic liposomes are potentially useful drug carrier to liver but may be affected by different modification.</p>

Preparation of 8-chloro-adenosine long circulation liposomes and its pharmacokinetics in rats / 药学学报

<p><b>AIM</b>To prepare 8-chloro-adenosine (8-Cl-A) long circulation liposomes with high entrapped efficiency and prolonged action-time of 8-Cl-A in vivo.</p><p><b>METHODS</b>To prepare 8-Cl-A long circulation liposomes of nanometer size by improved multiple emulsion. The entrapped efficiency, size and size distribution of 8-Cl-A long circulation liposomes were determined, and its pharmacokinetics in rats was evaluated.</p><p><b>RESULTS</b>The entrapped efficiency of 8-Cl-A long circulation liposomes was 62.70% and mean diameter of the liposomes was 79.9 nm. The pharmacokinetics studies indicated that 8-Cl-A long circulation liposomes showed higher drug concentration and larger AUC values than that of 8-Cl-A after iv to rats.</p><p><b>CONCLUSION</b>8-Cl-A long circulation liposomes could prolong the action-time of 8-Cl-A in vivo.</p>

Cholesteryl hemisuccinate as liposomal membrane stabilizer and its use in the preparation of saikosaponin-D liposomes / 药学学报

<p><b>AIM</b>To study the membrane stabilization effect and mechanism of cholesteryl hemisuccinate (CHEMS) on dipalmitoylphosphatidylcholine (DPPC) liposomes; Saikosaponin-D (SSD) liposomes were prepared by using CHEMS as a membrane stabilizer and its encapsulation efficiency and hemolytic activity were evaluated.</p><p><b>METHODS</b>Differential scanning calorimetry (DSC) and calcein release were used to study membrane stabilization effect of CHEMS on DPPC membrane, Fourier transform infrared spectroscopy (FT-IR) was used to study the interacting mechanism of CHEMS with DPPC, sedimentation experiment was done to study the interaction of CHEMS with SSD and hemolytic study was used to evaluate the hemolytic activity of SSD-liposomes with CHEMS as membrane stabilizer.</p><p><b>RESULTS</b>DSC analysis showed that CHEMS and cholesterol (CHOL) could all decrease the Tm value slightly and the deltaH value markedly. CHEMS was more effective than CHOL in decreasing the deltaH value of DPPC membrane. It suggested that CHEMS was more effective in increasing DPPC membrane stability. It was also proved by calcein release study carried out both in PBS and 30% plasma. The findings by FT-IR suggested that CHEMS has both hydrogen bond and electrostatic interaction with the polar head of DPPC. CHEMS did not form insoluble complex (INCOM) with SSD by sedimentation experiment. Stable SSD-liposomes were prepared using DPPC and CHEMS and decreased effectively the hemolytic activity of SSD, SSD-liposomes may be given intravenously at a concentration of 15 microg x mL(-1), while free SSD was forbidden to be given intravenously.</p><p><b>CONCLUSION</b>CHEMS was more effective than CHOL in increasing DPPC membrane stability, and it could be of great use in the preparation of cholesterol-dependent hemolytic saponins-liposomes. The hemolytic activity of SSD-liposomes was greatly reduced, allowing a possible concentration of 15 microg x mL(-1) to be intravenously administered.</p>

Biodistribution and hepatocytes targeting of cationic liposomes surface-modified with sterylglucoside and golyethylene glycol / 药学学报

<p><b>AIM</b>To investigate the biodistribution and the hepatocytes targeting of cationic liposome containing 3beta[N-( N',N'-dimethylaminoethane) carbamoyl] cholesterol (DC-Chol) and surface-modified liposomes with sterylglucoside (SG) and polyethylene glycol-distearoylphosphatidylethanolamine (PEG-DSPE).</p><p><b>METHODS</b>Cationic liposomes (CL) composed of DC-Chol and dipalmitoylphosphatidylcholine (DPPC), SG/PEG modified cationic liposome (SG/PEG-CL), both contained trace 3H-cholesterol (3H-Chol) as radiolabel, were prepared. The liposomes encapsulating 125I-labled antisense oligodeoxynucleotide (125I-asODN) (SG/PEG-CL-asODN) were also prepared. The biodistribution of CL, SG/PEG-CL, SG/PEG-C2-asODN as well as 125I-asODN solution, were studied. The radioactivities in hepatocytes and non-hepatocytes after administration of CL and SG/PEG-CL were determined by infuseing method.</p><p><b>RESULTS</b>CL and SG/PEG CL significantly aggregated in liver. The distribution of SG/PEG CL was significantly higher in hepatocytes (P < 0.01) and lower in non-hepatocytes (P < 0.01) than that of CL. The concentrations of SG/PEG-CL-asODN in liver and spleen were significantly higher than that of asODN solution (P < 0.01).</p><p><b>CONCLUSION</b>Cationic liposome modified with SG/PEG changed the distribution of asODN. Cationic liposome can target hepatocytes more effective after being modified with SG.</p>

Preparation of cisplatin multivesicular liposomes and release of cisplatin from the liposomes in vitro / 药学学报

<p><b>AIM</b>To prepare cisplatin multivesicular liposomes with high encapsulation efficiency and sustained-release character, and compare the release characteristics with conventional liposomes prepared by reverse-phase evaporation method.</p><p><b>METHODS</b>Cisplatin multivesicular liposomes were prepared using multiple emulsion method. The concentrations of cisplatin and lipids in the liposomes were measured by flameless atomic absorbance spectroscopy (FAAS) and phosphalipid enzyme reagent method, respectively. The encapsulation efficiency, size and release of the cisplatin from the liposomes were studied in vitro.</p><p><b>RESULTS</b>The mean diameter of cisplatin multivesicular liposomes was (16.6 +/- 1.0) micron. The encapsulation efficiency of cisplatin was more than 80%. The release profile in vitro fitted with a first-order equation. The releasing t1/2 of cisplatin multivesicular liposomes is 37.7 h, which is 8.4 that of conventional liposomes. Co-membrane stabilizer has remarkable stabilizing effect on the multivesicular liposomal membrane confirmed by differential scattering calorimetry (DSC).</p><p><b>CONCLUSION</b>The cisplatin multivesicular liposomes showed high encapsulation efficiency and sustained-release character.</p>