Therapeutic drugs cellular uptake

The concept of de-PEGylation can be applied to the development of nanoparticle-based drug delivery systems. PEG is used for the modification of liposomes to increase their blood circulation time [38], However, it also prevents cellular uptake, resulting in a decrease in therapeutic efficiency thus, modifications of the liposome surface with PEG interfere with membrane fusion to the cell membrane and liposome decomposition [39]. One of the possible strategies to solve this problem is to cleave the PEG chains after the nanoparticle reaches the target site (Fig. 9). This system of de-PEGylation of liposomes is also useful in avoiding the immune... 

Cannabidiol (CBD) is a non-psychotropic component of cannabis with possible therapeutic use as an anti-inflammatory drug. Recent studies on both enantiomers of CBD showed enantioselectivity in their interaction with cannabinoid and vanniloid (VRl) receptors as well as on the cellular uptake and enzymatic hydrolysis of anandamide (Bisogno et al. 2001). 

The control of inverse transition temperatures by sequence manipulation and biocompatibility of ELPs make them useful polymers for drug delivery. Cultured cancer cells and solid tumors in animal models uptake fluorescently labeled ELPs in a thermally responsive manner (48,49). Two major limitations in cancer therapy have been the inability of therapeutic molecules to cross the cell membrane and the target-specificity of the compounds. To overcome these limitations cell-penetrating, peptides (CPP) have been fused with ELPs (CPP-ELP) to develop thermally responsive therapeutics with the ability to translocate the cell membrane (Figure 3B). CPPs can assist in the transportation of hydrophilic compounds (small molecules, oglionucleotides and peptides) across the cell membrane (50). Fusing ELPs to a variety of CPPs have revealed that the peptide sequence of penetratin demonstrates the most efficient cellular uptake (51). Further, these CPP-ELPs have been fused to a c-Myc inhibitory peptide known to target and inhibit cancer. As proof of principle, these fusion proteins inhibits proliferation of cultured cancer cell lines in a thermally responsive manner (52). 

HA has been shown to produce synergistic therapeutic effects when coadministered with 5-fluorouracil (5-FU) and with PTX. HA formulated with 5-FU enhanced the cellular uptake and cytotoxicity of the drug compared to unformulated 5-FU (98). A similar effect has been observed when PTX was coadministered with HA (99). The admixture of PTX and HA significantly reduced the migration of Lewis lung carcinoma cells in a synergistic fashion and markedly improved the life span of mice seeded with tumor cells compared with PTX alone or HA alone. 

Cationic polymers mediate transfection via the condensation of nucleic acids, provide protection from enzymatic degradation, and facilitate cellular uptake and endolysosomal escape, making them an excellent candidate for gene delivery. However, their development has also expanded to other applications including drug conjugation and delivery, tissue engineering and therapeutic applications. 

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