DSPE-mPEG

Purpose:To employ Doxorubicin-loaded liposomes, modified with YSA-peptide to target EphA2, to reduce adverse effects against primary bone cells and maximize toxicity against Saos-2 osteosarcoma cells.Methods:PEGylated liposomes were prepared by thin film method using Dipalmitoylphosphatidylcholine (DPPC), cholesterol and distearylphosphatidylethanolamine-polyethyleneglycol conjugate (DSPE-mPEG) in 67.9:29.1:3 M ratios, and loaded with DOX (L-DOX) by pH-gradient method. Targeted liposomes (YSA-L-DOX), were prepared by conjugating YSA-peptide to DSPE-mPEG. Liposomes were physicochemically characterized and tested in cellular toxicity assays.Results:YSA conjugation efficiency was >98%. Size and polydispersity index of both L-DOX and YSA-L-DOX were around 88 nm and 0.188, respectively. Both had similar zeta potential, and 85% DOX loading efficiencies. DOX release kinetics followed the Korsmeyer-Peppa model, and showed comparable release for both formulations from 1-8 h, and a plateau of 29% after 48 h. Both formulations could be stably stored for ≥6 months at 4°C in the dark. Toxicity assays showed a significant 1.91-fold higher cytotoxicity compared to free DOX in the Saos-2 cells, and 2-fold lesser toxicity in primary bone cells compared to the Saos-2 cells. Cellular uptake studies showed higher and more nuclear uptake in YSA-L-DOX compared to L-DOX treated cells.Conclusions:YSA-L-DOX vesicles might be effective for targeted treatment of osteosarcoma.

As a structural analog of graphene and boron nitride, hexagonal boron carbonitride nanosheets (BCNNSs) are supposed to be a potential drug deliverer. In the present work, an improved solid-state reaction method combined with ultrasonic exfoliating was reported for preparing BCNNSs. Vapor-solid (VS) mechanism was proposed to be responsible for the formation of BCNNSs. The BCNNSs were further modified by DSPE-mPEG-5000 to improve their dispersion in aqueous solution. It was found that the BCNNSs-PEG nanocomplex could be efficiently taken in by MDA-MB-231 breast cancer cells evidenced by inverted fluorescence microscopy. The PEGylated BCNNSs showed an outstanding ability to load paclitaxel through π-π interaction and hydrophobic interaction, and BCNNSs-PEG-loaded paclitaxel presented higher cytotoxicity in comparison with free paclitaxel. BCNNSs may become a promising candidate for delivering paclitaxel and other hydrophobic drugs.

Objective:To develop a pirarubicin (THP) and vinorelbine (VRL) codelivery nano-micellar system (T+V-CS micelles) of pirarubicin (THP) and vinorelbine (VRL) by using chondroitin sulfate-cholesterol polymers (CS-Chol) and DSPE-mPEG2000and to evaluate the therapeutic efficacy of the codelivery nano-micelles in breast cancer treatment.Methods:T+V-CS micelles were prepared by ultrasonic-dialysis method, and the physicochemical characterization were evaluated using multiple technological means. The anti-tumor efficacy of T+V-CS micellesin vitrowas evaluated by MTT assay and cell cycle arrest analysis. Evaluation of the therapeutic effect of T+V-CS micellesin vivowas carried out on xenograft 4T1 murine breast cancer bearing BALB/c mice model.Results:T+V-CS micelles displayed a nearly spherical shape when observed through transmission electron microscope. The particle size and polydispersity indexes (PDI) of T+V-CS micelles was (155.5±4.5) nm and 0.170±0.003 respectively, while the Zeta potential was (-23.0±0.9) mV. Meanwhile, T+V-CS micelles demonstrated high encapsulation efficiency of (81.87±2.56)% for THP and (87.54±2.82)% for VRL and a high overall drug loading efficiency of (10.20±1.20)%.In vitroandin vivostudies of the therapeutic efficacy of breast cancer showed that T+V-CS micelles had synergistic anti-tumor effect and induced increased G2/M cell cycle arrest in 4T1 cells, which could significantly inhibit tumor growth and prolong survival compared with the therapeutic efficacy of micelles loaded with a single kind of drug or free drug solutions.Conclusion:The study showed that T+V-CS micelles had excellent anti-tumor effect, offering a reference to the clinical treatment of breast cancer.

The insertion of specific derivatives into pre-formed colloidal systems has been shown to be a useful method for modifying their pharmacokinetic characteristics and biodistribution profiles. In this experimental work the effect of the post-insertion of different PEG-derivatives into pre-formed 100-nm liposomes made up of various lipid mixtures (DMPC, DPPC, DOPC, DSPC and cholesterol at different molar ratios) was investigated. The vesicles were incubated with increasing amounts of DSPE-mPEG2000as sterically stabilized micelles (5, 10 and 15% w/w with respect to the liposomal lipid mixture) in order to favour the insertion of the PEG-lipid into the liposomal bilayer. The colloidal formulations were characterized by photo-correlation spectroscopy; the DSPE-mPEG2000integrated into the pre-formed liposomes was demonstrated by means of field flow fractionation while the amount of post-inserted compound was quantified using a suitable spectrophotometric assay (I2assay). Similar investigations have been performed using PEG-derivatives characterized by a different molecular weight. The physico-chemical properties of the various liposomal formulations were influenced by the post-insertion of PEG-derivatives. The lipid mixture made up of saturated phospholipids and cholesterol proved to be the best, post-insertion (P.I.E.). The post-insertion technique may be a suitable approach to be used in personalized (nano)medicine.