polidocanol and Lung-Neoplasms

Antitumor effects of hybrid liposomes (HL) composed of l-α-dimyristoylphosphatidylcholine (DMPC) and polyoxyethylene(23) dodecyl ether (C₁₂(EO)₂₃) on the metastatic growth of murine osteosarcoma (LM8) cells were investigated in vitro and in vivo. Remarkable inhibitory effects of HL-23 on the growth of LM8 cells were obtained through the induction of apoptotic cell death in vitro. It was also indicated that HL-23 should dramatically suppress the invasion of LM8 cells and the formation of filopodia on the cell surface in vitro. Furthermore, significantly high therapeutic effects were observed in the homograft mouse models of LM8 cells with lung metastasis after the treatment with HL-23 in vivo. That is, the histological analysis demonstrated that the primary tumor growth of LM8 cells implanted subcutaneously into the mice was inhibited along with the induction of apoptosis. In addition, it was found that HL-23 significantly decreased the lung metastasis of LM8 cells in the mouse models through the inhibition of primary tumor invasion. These results suggest that HL-23 could be a novel agent for the chemotherapy of osteosarcoma.

Topics: Animals; Apoptosis; Bone Neoplasms; Cell Line, Tumor; Dimyristoylphosphatidylcholine; Liposomes; Lung Neoplasms; Mice; Mice, Inbred BALB C; Osteosarcoma; Polidocanol; Polyethylene Glycols; Random Allocation

Multidrug resistance (MDR) is a major barrier to the chemotherapy treatment of many cancers. However, some nonionic surfactants, for example, Brij, have been shown to restore the sensitivity of MDR cells to such drugs. The aim of this study was to explore the reversal effect of Brij on MDR tumor cells and elucidate its potential mechanism. Our data indicate that the structure of Brij surfactants plays an important role in overcoming MDR in cancer, that is, modified hydrophilic-lipophilic balance (MHLB, the ratio of the number (n) of hydrophilic repeating units of ethylene oxide (EO) to the number (m) of carbons in the hydrophobic tail (CH(2))). Cell viability of cells treated with paclitaxel (PTX) nanocrystals (NCs) formulated with Brij showed positive correlations with MHLB (R(2) = 0.8195); the higher the ratio of Brij to PTX in NCs, the higher cytotoxicity induced by the PTX NCs. Significant increases in intracellular accumulation of (3)H-PTX (P-gp substrate) were observed in an MDR cell line (H460/taxR cells) treated with Brij 78 (MHLB = 1.11) and Brij 97 (MHLB = 0.6). After treatments with Brij 78 and Brij 97, the levels of intracellular ATP were decreased and verapamil-induced ATPase activities of P-gp were inhibited in multidrug resistant cells. The responses of the cells to Brij 78 and Brij 97 in ATP depletion studies correlated with the cell viability induced by PTX/Brij NCs and intracellular accumulation of (3)H-PTX. Brij 78 and Brij 97 could not alter the levels of P-gp expression detected by Western blotting. These findings may provide some insight into the likelihood of further development of more potent P-gp inhibitors for the treatment of MDR in cancer.

Topics: Adenosine Triphosphatases; Adenosine Triphosphate; Antineoplastic Agents, Phytogenic; ATP Binding Cassette Transporter, Subfamily B, Member 1; Biological Transport; Calcium Channel Blockers; Cell Line, Tumor; Cell Survival; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Humans; Hydrophobic and Hydrophilic Interactions; Lung Neoplasms; Nanoparticles; Paclitaxel; Plant Oils; Polidocanol; Polyethylene Glycols; Surface-Active Agents; Verapamil

Hybrid liposomes can be prepared by simply ultrasonicating a mixture of vesicular and micellar molecules in aqueous solution. A clear solution of hybrid liposomes composed of 90 mol% dimyristoylphosphatidylcholine (DMPC) and 10 mol% polyoxyethylene(23)dodecyl ether (C12(EO)23) having a hydrodynamic diameter of 100-120 nm was obtained. Highly inhibitory effects of hybrid liposomes of 90 mol% DMPC/10 mol% C12(EO)23 on the growth of human lung carcinoma (RERF-LC-OK and A549) cells without any drugs were obtained. Induction of apoptosis by hybrid liposomes in RERF-LC-OK and A549 cells was verified on the basis of fluorescence microscopy, agarose gel electrophoresis of DNA and flow cytometry. We elucidated the pathway of apoptosis induced by hybrid liposomes as follows: (a) accumulation of hybrid liposomes in tumor cell membrane was revealed using microphysiometer. (b) Reduction of mitochodrial membrane potential and activation of caspase-9, -3 and -8 were obtained, indicating that apoptotic signal by hybrid liposomes should pass through mitochondria and these caspases. It is worthy to note that such a novel mechanism of apoptosis induced by hybrid liposomes without any drugs was performed for the first time in human lung carcinoma cells.

Topics: Biosensing Techniques; Caspases; Cell Line, Tumor; Cell Membrane; Cell Proliferation; Dimyristoylphosphatidylcholine; DNA Fragmentation; Drug Screening Assays, Antitumor; Humans; Liposomes; Lung Neoplasms; Microscopy, Fluorescence; Nanotechnology; Polidocanol; Polyethylene Glycols; Signal Transduction; Technology, Pharmaceutical

Bronchial fistula is one of the most serious complications of pulmonary resection.. We present an endoscopic treatment that consists of multiple submucosal injections of polidocanol-hydroxypoliethoxidodecane (Aethoxysklerol Kreussler) on the margins of the fistula using an endoscopic needle inserted through a flexible bronchoscope.. From 1984 to 1995, 35 consecutive nonselected patients with a postresectional bronchopleural fistula were treated. All 23 partial postpneumonectomy or postlobectomy bronchopleural fistulas, ranging from 2 to 10 mm in diameter, healed completely. This did not occur in the 12 total bronchial dehiscences. No complications occurred due to the injection of the drug.. In our opinion this treatment can be considered a valid therapeutic approach, as it is simple, safe, scarcely traumatic, and inexpensive, particularly considering that, in patients in stable condition, it can be performed as an outpatient treatment.

Topics: Bronchial Fistula; Bronchoscopy; Endoscopy; Fistula; Humans; Injections; Lung Neoplasms; Pleural Diseases; Pneumonectomy; Polidocanol; Polyethylene Glycols; Postoperative Complications; Surgical Wound Dehiscence; Tissue Adhesives; Treatment Outcome