Cancer cell membrane-coated bacterial ghosts for highly efficient paclitaxel delivery against metastatic lung cancer

Chemotherapy is one of the major approaches for the treatment of metastatic lung cancer, although it is limited by the low tumor delivery efficacy of anticancer drugs. Bacterial therapy is emerging for cancer treatment due to its high immune stimulation effect; however, excessively generated immunogenicity will cause serious inflammatory response syndrome. Here, we prepared cancer cell membrane-coated liposomal paclitaxel-loaded bacterial ghosts (LP@BG@CCM) by layer-by-layer encapsulation for the treatment of metastatic lung cancer. The preparation processes were simple, only involving film formation, electroporation, and pore extrusion. LP@BG@CCM owned much higher 4T1 cancer cell toxicity than LP@BG due to its faster fusion with cancer cells. In the 4T1 breast cancer metastatic lung cancer mouse models, the remarkably higher lung targeting of intravenously injected LP@BG@CCM was observed with the almost normalized lung appearance, the reduced lung weight, the clear lung tissue structure, and the enhanced cancer cell apoptosis compared to its precursors. Moreover, several major immune factors were improved after administration of LP@BG@CCM, including the CD4+/CD8a+ T cells in the spleen and the TNF-α, IFN-γ, and IL-4 in the lung. LP@BG@CCM exhibits the optimal synergistic chemo-immunotherapy, which is a promising medication for the treatment of metastatic lung cancer.

Preparation and evaluation of enrofloxacin microspheres and tissue distribution in rats

New enrofloxacin microspheres were formulated, and their physical properties, lung-targeting ability, and tissue distribution in rats were examined. The microspheres had a regular and round shape. The mean diameter was 10.06 microm, and the diameter of 89.93% of all microspheres ranged from 7.0 microm to 30.0 microm. Tissue distribution of the microspheres was evaluated along with a conventional enrofloxacin preparation after a single intravenous injection (7.5 mg of enrofloxacin/kg bw). The results showed that the elimination half-life (t(1/2beta)) of enrofloxacin from lung was prolonged from 7.94 h for the conventional enrofloxacin to 13.28 h for the microspheres. Area under the lung concentration versus time curve from 0 h to infinity (AUC(0-infinity)) was increased from 11.66 h.microg/g to 508.00 h.microg/g. The peak concentration (Cmax) in lung was increased from 5.95 microg/g to 93.36 microg/g. Three lung-targeting parameters were further assessed and showed that the microspheres had remarkable lung-targeting capabilities.

Tissue distribution of lung targeting Doxorubicin microspheres in mice / 中国药学杂志

OBJECTIVE: To study the tissues distribution of lung targeting Doxorubicin microspheres in mice. METHODS: doxorubicin microspheres were prepared by emulsification-linkage method, and their characteristics was studied. The tissue distribution of doxorubicin microspheres was investigated via caudal vein injection in mice by high performance liquid chromatography. And the targeting character of microspheres was evaluated. RESULTS: Doxorubicin microspheres were orange and regular. Microspheres with diameters of 5 - 15 μm occupied 85.5%, and the loading amount was 4.05%. The re, te and Ce of doxorubicin microspheres was 2.21 times, 1.97 -3.36 times and 1.68 times larger than those of doxorubicin control solution. And the tissue section also indicated that there were more microspheres in the lung tissue. CONCLUSION: Doxorubicin microspheres can target at the lung tissue of miceand reduce the accumulation in heart, which can improve curative effects and reduce toxicity. Copyright 2012 by the Chinese Pharmaceutical Association.

Preparation and evaluation of lung targeting microspheres for protionamide in vitro and in vivo / 中国药学杂志

OBJECTIVE: To testify the feasibility of targeted delivery of protionamide to lung through the iv administration of the biodegradable poly(lactic-co-glycollic acid) (PLGA) microspheres. METHODS: Based on the single-factor study, the preparation of protionamide-PLGA microspheres was optimized. The surface morphology of the microspheres was observed by scanning electron microscope (SEM). The mean diameter and the size distribution of microsphere, the drug loading, the incorporation efficiency, drug release in vitro, stability and tissue distribution after intravenous administration were also evaluated, respectively. RESULTS: Protionamide-PLGA microspheres were regular and spherical in shape. The average particle size was (9.86 ± 1.38) μm and over 81.53% of the microspheres was in the range of 7-15 μn. The drug loading and encapsulated ratio was (32.70 ± 0.37)% and (8.48 ± 0.24)%, respectively. The in vitro drug release could be well fitted by the Higuchi equation (Q=4.4303t1/2 ± 7.7241, r=0.9913). Compared with the aqueous formulation, the drug level in lung of BALB/C mice in microsphere group was much higher, and also kept for longer time. CONCLUSION: The protionamide-PLGA microspheres prepared in this study show significant sustained release and lung targeting effect.

Preparation of Hydroxycampothecinum Microspheres and Its Distribution in Mice / 中国药房

OBJECTIVE:To prepare lung-targeting hydroxycampothecinum(HCPT) microspheres and evaluate its in vitro release characteristics and its lung-targeting property in mice.METHODS:The microspheres was prepared by solvent volatilization with polylactic acid as chief excipient.The particle size,entrapment efficiency(EE) and drug loading(DL) of the microspheres were studied and the in vitro release rate was compared with that of the crude drug.12 mice enrolled were injected via vena caudalis with HCPT micropheres or HCPT crude drug,at 30 min,the drug level in plasma and tissues were determined and the relative distribution rates(RDR) were computed.RESULTS:81.6% of the microspheres ranged from 7～ 30 ?m in particle size,the mean diameter was (14.2?3.1) ?m,the EE was 72.36%,the DL was (40.6?3.6)%,and the in vitro drug release parameter T50 was 85 min for microspheres vs.18 min for crude drug.The drug level of the microspheres in lung was the highest at (32.2?2.48) ?g?mL-1 with a RDR of 58.1%;The drug level of the crude drug group in plasma was the highest at (13.52?2.58) ?g?mL-1 with a RDR of 25.24%.CONCLUSION:The prepared HCPT microspheres had the distinctive characteristics of sustained-release and lung targeting.

Distribution and Pharmacokinetics of Lung Targeting Etoposide-bovine Serum Albumin-microspheres in Mice / 中国药房

OBJECTIVE:To prepare etoposide-bovine serum albumin-microspheres (VP-BSA-MS)and to study the distribution and pharmacokinetics of VP-BSA-MS in mice. METHODS: The drug concentrations in various tissues were determined by high-performance liquid chromatograph (HPLC). RESULTS: The VP-BSA-MS was injected into mice and (47.88?2.56 )% of the total dosage was detected in lung tissue 15min after administration,the pharmacokinetical equation was C=149.0 897e-1.7 780t+3.9 627e-0.0 398t —153.0 524e-3.5 054t. CONCLUSION:The VP-BSA-MS showed remakable targeting action to the lung and the pharmacokinetic regularity could be discribed as two-compartment model