ABSTRACT
A mixed drug self-delivery system(DSDS)with high drug content(＞50％)was developed to regulate pH-triggered drug release,based on two doxorubicin(DOX)-DOX dimmers:D-DOXADH and D-DOXcar con-jugated with acid-labile dynamic covalent bonds(hydrazone and carbamate,respectively)and stabilized with PEGylated D-DOXADH(D-DOXADH-PEG).Owing to the different stability of the dynamic covalent bonds in the two dimers and the noncovalent interaction between them,pH-triggered drug release could be easily regulated by adjusting the feeding ratios of the two DOX-DOX dimers in the mixed DSDS.Similar in vitro cellular toxicity was achieved with the mixed DSDS nanoparticles prepared with different feeding ratios.The mixed DSDS nanoparticles had a similar DOX content and diameter but different drug releasing rates.The MTT assays revealed that a high anti-tumor efficacy could be achieved with the slow-release mixed DSDS nanoparticles.
ABSTRACT
@#Modulating drug release from liposomes at tumor sites are important for eliciting therapeutic effects of platinum drugs considering their low permeability through liposomal membranes, here a novel secretory phospholipase A2 (sPLA2) responsive-liposome system was constructed for oxaliplatin (L-OHP).Lipid ingredients dipalmitoyl phosphatidylcholine and distearoyl phosphoethanolamine-PEG2k, together with facial amphiphiles (FAs) including lithocholic acid (LCA) or 3-keto lithocholic acid (kLCA) were used to prepare sPLA2 responsive-liposome (LCA-Lip or kLCA-Lip) by thin-film hydration method.The physicochemical properties, sPLA2-responsive drug release and anti-tumor activity were evaluated in vitro.The results indicated L-OHP loaded liposomes modified with FAs had similar particle sizes of approximately 100 nm and narrow size distributions (PDI < 0.11).Compared with non-FAs-containing liposomes (C-Lip), LCA-Lip or kLCA-Lip has a comparable entrapment efficiency and loading efficiency.LCA-Lip or kLCA-Lip didn't show significant higher drug leakage at the presence of 10% or 50% fetal bovine serum (FBS) in media than that in media without FBS.Treated with secretory phospholipase A2 from Colo205 cells culture conditioned medium (CCM sPLA2) for 24 h, FAs modified liposomes released about 70% of carboxyfluorescein (CF), while C-Lip only released 20% of CF.Compared to L-OHP loaded C-Lip, L-OHP-loaded FAs-included formulations had much greater anti-proliferative activity against sPLA2-secreting Colo205 cells.In summary, our results shows that LCA or kLCA promotes responsiveness of liposomes to tumor-related sPLA2 and points to a new way to develop platium drugs-loaded liposomal delivery systems with better release mechanisms.
ABSTRACT
@#Currently the available therapies cannot satisfy all the clinical requirements, therefore advanced technologies are urgently demanded. Delivery system the polymeric prodrug based has both advantages of prodrug strategy and nanoparticle drug delivery strategy. The system can improve the drug bioavailability, enhance the drug stability, and make the drug targeting system more effective. The system can reduce the side effects and improve the therapeutic effect of drug. According to the mechanism of this drug system, passive targeting, active targeting, triggered release and co-administration were reviewed. Finally, the research prospects and issues in this field were pointed out.
ABSTRACT
With the development of polymeric materials and nanotechnology, the potential application of nanoscaled drug delivery system (NDDS) is gradually manifested in the field of pharmaceutics. Especially, NDDS has the obvious advantages in the delivery of gene or drug. Comparing to the delivery system of single-drug, co-delivery system of gene and drug can significantly improve the therapeutic effects by enhancing transfection efficiency of gene and reversing multidrug resistance, etc. The co-delivery systems of gene and drug, which had the triggered release characteristics in the inner and outer of tumor, could be constructed by introducing the environment-responsive (pH-responsive, redox-responsive and light-responsive, etc) groups into the co-delivery system. The antitumor activity was further improved. In the present paper, the environment- responsive delivery systems in the application of co-delivery gene and drug in recent years were reviewed, and their remarkable properties in the antitumor activity were analyzed and summarized.