Polymeric micelles for enhanced lymphatic drug delivery to treat metastatic tumors

Pulmonary delivered polymeric micelles – Pharmacokinetic evaluation and biodistribution studies

“…The increased distribution to the brain and lymph nodes might be attributed to the ability of micelles to penetrate across the BBB [48] and to accumulate in the lymphatic system via extravasation [49]. The fact that IT micelles can translocate across the air-blood barrier to the blood and penetrate into the brain suggests that pulmonary delivery may be able to non-invasively achieve brain targeting with nanocarriers.…”

Small-sized polymeric micelles incorporating docetaxel suppress distant metastases in the clinically-relevant 4T1 mouse breast cancer model

“…The in vitro release behavior of SPM presented as the cumulative percentage release is shown in Figure  1F. The aforementioned polymer-metal complex formation between DACHPt and the carboxylic group of the P(Glu) in the PEG- b -P(Glu) led to the formation of polymeric micelles with the average diameters of approximately 30 nm [21], while doxorubicin and vinorelbine can be tightly packaged into small-sized PEG-PE-based micelles due to the amphiphilic nature of the drugs and PEG-PE molecules and their specific structures [20]. The ability of a micelle system to function as a solubilizer or a true carrier depends on its stability and the diversity of polymer chemistry can provide a custom fit to drug molecules to be loaded [23].…”

“…To validate the bioluminescence results in Figure  4A, lung foci were apparent as white nodules following immersion of the lungs in Bouin’s fixative for 24 h. The number of tumor nodules was taken as an indicator of varying metastasis in a previous study of tumor cell colonization in the lungs [20]. However, it cannot reflect the metastatic situation in the lung adequately because of differences in tumor nodule sizes; i.e., lungs with more but smaller nodules do not necessarily indicate more advanced metastasis than lungs with fewer but larger metastatic nodules.…”

“…In this study, we prepared SPM, an mPEG 2000 - b -PDLLA 1300 -based DTX polymeric micelle formulation with a particle size (i.e., 10–30 nm) previously shown to result in maximal accumulation in lymph nodes [20,21]. Compared with free DTX (Duopafei), SPM was more effective in inhibiting the growth of 4T1 tumor cells in vitro by inducing late apoptosis.…”

Targeting tumor metastases: Drug delivery mechanisms and technologies

“…A number of studies have suggested that the lower size end of therapeutic nanoparticles may be beneficial for this application. For example, sub-50 nm polymeric micelles have been used to deliver platinum-based chemotherapies to lymph and brain metastases [87, 88], while ∼15 nm particles were used to deliver doxorubicin successfully to breast cancer metastases in the lymph [89]. In addition to size, targeting of lymph can be accomplished using the LyP-1 peptide, which localizes with lymphatic endothelium and tumor associated macrophages.…”