However, at 16 hours p.i., a clear difference is observed in the accumulated doxorubicin tumor concentrations, confirming earlier findings that efficacy improves with CTT2-peptide-bound liposomal

delivery systems. The extended times of accumulation may be a consequence of the different liposomal formulations used. Doxorubicin concentrations, in the form of CTT2-SL-DSPE-PEG3400 liposomes, continued Inhibitors,research,lifescience,medical to rise at later time points, as against the notable decreases in tumor concentrations observed with the untargeted CTT2-Caelyx-like liposomes. Future kinetic studies should monitor time-varying changes in tumor doxorubicin concentrations (in the form of CTT2-peptide targeted liposomes) at delayed time intervals (i.e., >16hrs p.i.) in order to determine whether antitumor efficacy studies could benefit from employing a dosing regimen reflecting longer, sustained tumor concentrations. Figure 11 Serum doxorubicin levels. Concentration of doxorubicin in (a) serum and (b) OV-90 xenograft mice Inhibitors,research,lifescience,medical (n = 3) treated with CTT2-SL-DSPE-PEG3400. Data are represented as a mean ± SEM. 4. Conclusions

Gelatinases, as extracellular targets, offer a viable alternative Inhibitors,research,lifescience,medical for tumor targeting. In gelatinase-expressing tumors, such as OV-90, targeted liposomal constructs, 125I-CTT2-SL and doxorubicin-containing CTT2, were found to be promising nanotherapeutic delivery vehicles for achieving therapeutic efficacy. Table 1 summarizes the tumor uptakes of various targeted and nontargeted liposomal formulations. Differences in tumor uptake were observed range ovarian cancer models, with Inhibitors,research,lifescience,medical the largest uptake values (i.e., ~17% ID/g at 6hrs) achieved in OV-90 hindlimb xenografts using CTT2-peptide-bound liposomes (~500 peptides per liposome). Further, CTT2-bound micelles and liposomes, as well as the CTT2 peptide, Inhibitors,research,lifescience,medical demonstrated equivalent overall tumor uptake values, suggesting similar

bioactivity. However, to achieve controlled and sustained drug release, we chose a nanoformulation instead of a prodrug approach (i.e., drug-peptide coupling). Our findings show that the utilization of these targeted nanoformulations results in a more efficient method for delivering therapeutics Adenosine than passive (i.e., nontargeted) liposomal products (i.e., Caelyx). The development of CTT2-peptide-bound liposomes as a clinically promising targeting therapeutic that has the potential to improve drug delivery to human ovarian cancers will rest on the additional assessment of shelf and in vivo stability studies and formal toxicity testing. Table 1 Tumor uptake of various liposomal constructs. ​ Figure 3 Schematic illustration of CTT2-PEG-3400-DSPE TGF-beta assay liposome [22].
Live cells are protected from the surrounding environment by the cell membrane, which only allows compounds with a small molecular size to pass this barrier into the cell. Some drug molecules, on the other hand, are large hydrophilic molecules, and this creates major limitations for their penetration through the cell membrane.