Thermo-Sensitive Liposome co-Loaded of Vincristine and Doxorubicin Based on Their Similar Physicochemical Properties had Synergism on Tumor Treatment.

PURPOSE: To develop vincristine (VCR) and doxorubicin (DOX) co-encapsulated thermo-sensitive liposomes (VD-TSL) against drug resistance, with increased tumor inhibition rate and decreased system toxicity, improving drug targeting efficiency upon mild hyperthermia (HT) in solid tumor. METHODS: Based on similar physicochemical properties, VCR and DOX were co-loaded in TSL with pH gradient active loading method and characterized. The time-dependent drug release profiles at 37 and 42°C were assessed by HPLC. Then we analysed the phospholipids in filtrate after ultrafiltration and studied VD-TSL stability in mimic in vivo conditions and long-time storage conditions (4°C and -20°C). Cytotoxic effect was studied on PANC and sw-620 using MTT. Intracellular drug delivery was studied by confocal microscopy on HT-1080. In vivo imaging of TSL pharmacokinetic and biodistribution was performed on MCF-7 tumor-bearing nude mice. And therapeutic efficacy on these xenograft models were followed under HT. RESULTS: VD-TSL had excellent particle distribution (about 90 nm), high entrapment efficiency (>95%), obvious thermo-sensitive property, and good stability. MTT proved VD-TSL had strongest cell lethality compared with other formulations. Confocal microscopy demonstrated specific accumulation of drugs in tumor cells. In vivo imaging proved the targeting efficiency of TSL under hyperthermia. Then therapeutic efficacy revealed synergism of VCR and DOX co-loaded in TSL, together with HT. CONCLUSION: VD-TSL could increase drug efficacy and decrease system toxicity, by making good use of synergism of VCR and DOX, as well as high targeting efficiency of TSL.

A novel drug-polyethylene glycol liquid compound method to prepare 10-hydroxycamptothecin loaded human serum albumin nanoparticle.

Drug loading strategies and the methods derived for implementing those strategies are crucially important to the preparation of drug loaded human serum albumin nanoparticles (HSA-NPs), because each of them is focused on wrapping up specific types of drugs via certain physical and chemical properties. However, poor adaptability still exists to load drugs like model substance 10-hydroxycamptothecin (HCPT) by conventional methods. Because it typically represents a large class of water-insoluble drugs, who also structurally possess a certain number of hydrophilic groups. So even though they majorly have lipophilicity but they are of low liposolubility. This article presents a new concept of a loading strategy that takes a drug polymer liquid compound as a loading medium. The drug polymer liquid compound was made from low weight polyethylene glycol (l-PEG) and HCPT. Consequently, this strategy has managed to fabricate HCPT-loaded HSA-NPs through an unconventional approach that overcomes drawbacks of current loading means and better results have been obtained, like high entrapment efficiency (over 99%) and less toxicity involvement. Afterward, in vitro and in vivo evaluations and characterizations were performed to help with the in-depth interpretation of the loading mechanism in order to reveal and further investigate the possible far-reaching applications of this method.