Combination Therapy of Lung Cancer Using Layer-by-Layer Cisplatin Prodrug and Curcumin Co-Encapsulated Nanomedicine.

PURPOSE: Lung cancer remains the leading cancer-associated deaths worldwide. Cisplatin (CDDP) was used in combination with curcumin (CUR) for the treatment of non-small cell lung cancer. The aim of this study was to prepare and characterize CDDP prodrug and CUR co-encapsulated layer-by-layer nanoparticles (CDDP-PLGA/CUR LBL NPs) to induce cooperative response, maximize the therapeutic effect, overcome drug resistance, and reduce adverse side effects. METHODS: CDDP prodrug (CDDP-PLGA) was synthesized. CDDP-PLGA/CUR LBL NPs were constructed and their physicochemical properties were investigated by particle-size analysis, zeta potential measurement, drug loading, drug entrapment efficiency, and in vitro drug release behavior. In vitro cytotoxicity against human lung adenocarcinoma cell line (A549 cells) was investigated, and in vivo anti-tumor efficiency of CDDP-PLGA/CUR LBL NPs was evaluated on mice bearing A549 cell xenografts. RESULTS: CDDP-PLGA/CUR LBL NPs have a size of 179.6 ± 6.7 nm, a zeta potential value of -29.9 ± 3.2 mV, high drug entrapment efficiency of 85.6 ± 3.9% (CDDP) and 82.1 ± 2.8% (CUR). The drug release of LBL NPs exhibited a sustained behavior, which made it an ideal vehicle for drug delivery. Furthermore, CDDP-PLGA/CUR LBL NPs could significantly enhance in vitro cytotoxicity and in vivo antitumor effect against A549 cells and lung cancer animal model compared to the single drug-loaded LBL NPs and free drug groups. CONCLUSION: CDDP-PLGA/CUR LBL NPs were reported for the first time in the combination therapy of lung cancer. The results demonstrated that the CDDP-PLGA/CUR LBL NPs might be a novel promising system for the synergetic treatment of lung carcinoma.

Lung cancer therapy using doxorubicin and curcumin combination: Targeted prodrug based, pH sensitive nanomedicine.

Lung cancer is the leading cause of cancer death worldwide. To overcome the toxic side effects and multidrug resistance (MDR) during doxorubicin (DOX) chemotherapy, a urokinase plasminogen activator receptor (uPAR) targeting U11 peptide decorated, pH-sensitive, dual drugs co-encapsulated nanoparticles (NPs) system is employed in this study. A U11 peptide conjugated, pH-sensitive DOX prodrug (U11-DOX) was synthesized and used as materials to produce NPs. A curcumin (CUR) and U11-DOX co-encapsulated NPs system (U11-DOX/CUR NPs) was constructed to treat lung cancer. After the characterization of biophysical properties of this NPs system, synergistic chemotherapeutic efficacy was evaluated in both cultured cancer cells and tumor-bearing animal model. U11-DOX/CUR NPs had a uniformly spherical shape with a core-shell structure. The mean particle size and zeta potential of the U11-DOX/CUR NPs was 121.3 nm and -33.5 mV, with a DOX and CUR EE of 81.7 and 90.5%, respectively. The DOX release from U11-DOX/CUR NPs was 83.5, 55.2, and 32.8% correspondence to the pH of 5.0, 6.0 and 7.4. Cellular uptake efficiency of U11-DOX/CUR NPs was significantly higher than non U11 peptide decorated DOX/CUR NPs. U11-DOX/CUR NPs displayed a pronounced synergy effects in vitro and an obvious tumor tissue accumulation efficiency in vivo. In vivo antitumor experiment showed that U11-DOX/CUR NPs could inhibit the tumor growth to a level of 85%.In vitro and in vivo studies demonstrated that U11-DOX/CUR NPs is a sustained released, pH responsive, synergistic antitumor system. This study suggests that the U11-DOX/CUR NPs have promising potential for combination treatment of lung cancer.

Clinical effects of lianbai liquid in prevention and treatment of dermal injury caused by radiotherapy.

OBJECTIVE: To observe the effect of Lianbai liquid in prevention and treatment of acute radiation dermal injury. METHOD: From May 2000 to December 2005, 126 cancer patients were randomly divided into a prevention group of 75 cases given externally topical application of Lianbai liquid since the first radiotherapy, and a control group I of 51 cases given only advice after radiotherapy; while the other 92 cancer patients who had already had grade III acute radiation-induced dermal injury were randomly divided into a treatment group of 54 cases treated by externally topical use of Lianbai liquid, and a control group II of 38 cases treated by topical use of norfloxacin. Clinical evaluation was carried out according to the CTC.V2.0 standard stipulated by NCI for classifying acute radiation dermal injury. RESULTS: The incidence of skin reaction was 32.0% in the prevention group and 92.2% in the control group I, with an obvious difference between the two groups (chi2=54.163, P<0.01). Mild radioactive reaction (grade I and II) was 28.0% (21/75) in the prevention group and 70.6% (36/51) in the control group I, with a remarkable difference between the two groups (chi2=22.226, P<0.01). The effective rate for grade III dermal injury was 92.6% (50/54) in the treatment group and 65.9% (25/38) in the control group II, with a remarkable difference between the two groups (chi2=6.018, P=0.024). The wound-healing time was 11.07+/-2.21 days in the treatment group and 18.08+/-1.76 days in the control group II, with a remarkable difference between the two groups (u=16.932, P<0.01). CONCLUSION: Lianbai liquid can effectively prevent the radiation dermatitis, and treat grade III acute radiation dermal injury with obvious curative effect.