betadex and 10-hydroxycamptothecin

Manufacturing and characterizing hydroxycamptothecin inclusion liposomes, establishing their quality standard and testing their in vitro anti-tumor activity is of significance for potential application. The neutralization agitation method was used to prepare hydroxycamptothecin inclusion and film evaporation method was utilized to manufacture hydroxycamptothecin inclusion liposomes. The phase solubility method, differential scanning calorimetry and infrared spectroscopy were used to identify the prepared inclusion complex. The hydroxycamptothecin inclusion liposomes were characterized for particle morphology, size, in vitro release and stability. The hepatoma (HepG-2), lung cancer (A549), and gastric cancer (SGC-7901) cell lines were used as models for preliminary evaluation of anti-cancer effect from the hydroxycamptothecin inclusion liposomes, done by MTT colorimetry, cytometer experiments, and apoptosis staining. The anti-cancer evaluation was compared with commercially available hydroxycamptothecin. The results showed the hydroxycamptothecin inclusion was successfully prepared by neutralization agitation method. Phase solubility method, differential scanning calorimetry and infrared spectroscopy proved the formation of the hydroxycamptothecin inclusion. The hydroxycamptothecin inclusion liposomes were successfully prepared by film evaporation method. (2) The inclusions were found to be spherical, with average particle size of 119.7 nm, zeta potential of - 45.6 mV, average inclusion rate of 70.55%, and drug-loading was 14.60%. The inclusions were also found to have a sustained release effect, when compared to the commercially available hydroxyccamptothecine. The hydroxyccamptothecine inclusion liposomes had better stability at 4 degrees. (3) The hydroxycamptothecin inclusion liposomes also exhibited better inhibition effect for the three kinds of cancer cell lines above, when compared to the commercially available hydroxycamptothecin the anti-cancer effect being at a dose-dependent manner. Neutralization agitation and thin film evaporation methods can be used to manufacture hydroxycamptothecin inclusion liposomes with better encapsulation efficiency, drug-loading content, stability, sustained-release effect and stronger anti-cancer activity.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; Antineoplastic Agents; Apoptosis; beta-Cyclodextrins; Camptothecin; Cell Line, Tumor; Hep G2 Cells; Humans; Liposomes

Emulsion electrospinning was used in the present study to prepare core-sheath structured fibers with core-loading of hydroxycamptothecin (HCPT), and their antitumor activities were evaluated both in vitro on cancer cell lines and in vivo on tumor bearing mice via intratumoral implantation. Compared with our previous investigation on blend electrospun fibers, the addition of 2-hydroxypropyl-β-cyclodextrin (HPCD) and the preferential formation of HPCT/HPCD inclusion complexes resulted in significantly faster HCPT release from and higher degradation rate of emulsion electrospun fibers. The core-sheath structure led to around 93% of lactone form remaining after emulsion electrospinning and incubation in buffer solutions for over one month. In vitro cytotoxicity tests on HCPT-loaded electrospun fibers indicated over 20 times higher inhibitory activity against HepG2 cells than free HCPT during 72h incubation. Hepatoma H22 cells were subcutaneously injected into Kunming mice to form solid tumors for in vivo tests on the antitumor efficacy. Based on the tumor volume, survival rate and body weight changes, HCPT-loaded fibers indicated superior in vivo antitumor activities to and fewer side effects than free HCPT. The histopathological staining and immunohistochemical examinations of caspase-3 expression indicated more necrosis and apoptosis induced by HCPT-loaded fibers. The above results demonstrate the potential use of emulsion electrospun fibers as drug carriers for local treatment of solid tumors.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; Animals; Antineoplastic Agents, Phytogenic; beta-Cyclodextrins; Camptothecin; Cell Line, Tumor; Cell Survival; Drug Carriers; Emulsions; Humans; Lactates; Mice; Neoplasm Transplantation; Neoplasms; Polyethylene Glycols; Tumor Burden

Hydroxycamptothecin (HCPT) is valid to various malignant tumors, but its insoluble and unstable lactone ring in physiological environment have restricted the clinic application. This work was aimed to formulate HCPT-loaded poly(DL-lactic acid)-poly(ethylene glycol) (PELA) fibrous mats through blend electrospinning with 2-hydroxypropyl-beta-cyclodextrin (HPCD) to modulate the drug release and matrix degradation, and to enhance the structural integrity and cytotoxicity of the released HCPT. The entire drug fraction retained its active lactone form within electrospun fibers, and that was maintained over 85% during incubation for over 1 month. A biphasic release pattern was determined for HCPT-loaded electrospun fibers, which can be modulated by the addition of HPCD. HPCD served as solubilizer to maintain a large concentration gradient for HCPT between saturation and diffusion, and liberated HPCD created microstructure of ultrafine fibers, leading a faster release profile in the second phase. In vitro cytotoxicity test showed over 7 times higher inhibitory activity against cancer cells for HCPT-loaded electrospun fibers than free drug during 72h incubation. Higher apoptosis rates and the arrest of the cell cycle during the S and G(2)/M phases were detected through flow cytometry analysis. It indicated therapeutic potentials of HCPT-loaded electrospun fibers as implantable anti-cancer agents for local chemotherapy.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; Antineoplastic Agents, Phytogenic; Apoptosis; beta-Cyclodextrins; Camptothecin; Cell Cycle; Cell Line, Tumor; Cell Survival; Drug Carriers; Drug Stability; Female; Humans; Lactates; Nanofibers; Nanotechnology; Polyethylene Glycols; Surface Properties