Cellular drug delivery

Schroder, T Schmitz, K., Niemeier, N et al. (2007) Solid-phase synthesis, bioconjugation, and toxicology of novel cationic oligopeptoids for cellular drug delivery. Bioconjugate Chem. ASAP Article DOI 10.1021/bc0602073. 

A.H. Faraji, P. Wipf, Nanoparticles in cellular drug delivery, Bioorg. Med. Chem. 17 (2009) 2950-2962. 

PLL-modified, hybrid-modified and unmodified PLGA nanoparticles were developed for cellular drug delivery to human lung adenocarcinoma A549 cells. Hybrid-modified nanoparticles were prepared using a cationic polymer, PLL, and a nonionic surfactant, polysorbate 80. Studies on the cellular uptake efficacy of hybrid-modified nanoparticles compared with PLL-modified and unmodified nanoparticles proved that PLL-modified... 

M. D. Chavanpatil, A. Khdair and J. Panyam, Nanoparticles for cellular drug delivery mechanisms and factors influencing delivery. /. Nanosci. NanotechnoL, 6(9-10), 2651-2663 (2006). 

Faraji, A. H. and Wipf, P. 2009. Nanoparticles in cellular drug delivery. BioorgMed Che 17 2950-62. 

Peptoid-Based Drug Delivery and Molecular Transporters Cellular Uptake... 

Alternatively, one interesting drug delivery technique exploits the active transport of certain naturally-occurring and relatively small biomacromolecules across the cellular membrane. For instance, the nuclear transcription activator protein (Tat) from HIV type 1 (HlV-1) is a 101-amino acid protein that must interact with a 59-base RNA stem-loop structure, called the traus-activation region (Tar) at the 5 end of all nascent HlV-1 mRNA molecules, in order for the vims to replicate. HIV-Tat is actively transported across the cell membrane, and localizes to the nucleus [28]. It has been found that the arginine-rich Tar-binding region of the Tat protein, residues 49-57 (Tat+9 57), is primarily responsible for this translocation activity [29]. 

Oehlke and coworkers have described the cellular uptake properties of a simple a-hehcal amphipathic model peptide sequence (Lys-Leu-Ala-Leu-Lys-Leu-Ala-Leu-Lys-Ala-Leu-Lys-Ala-Ala-Leu-Lys-Leu-Ala) in the context of a drug delivery vehicle [72]. On the basis of the data presented, it was proposed that non-endocytosis mechanism(s) were involved in the uptake into mammalian cells. The similarity between our b2 aPNA-sequence to that of this amphipathic model peptide makes it tempting to suggest that a similar uptake mechanism is involved in the cellular uptake of aPNAs. Further experimentation is necessary to test this hypothesis. 

Liposomes that remain impermeable to their contents cannot release these compounds without interaction with cells. This cellular interaction occurs by three different mechanisms (Fig. 11) [57], Of these, fusion and adsorption usually involve drug leakage, whereas effective drug delivery results from en-docytosis. 

The potential of liposomes in oral drug delivery has been largely disappointing. However, the use of polymer-coated, polymerized, and microencapsulated liposomes have all increased their potential for oral use [63], and it predicted that a greater understanding of their cellular processing will ultimately lead to effective therapies for oral liposomes. 

C. R. Hopkins, Site-specific drug delivery—cellular opportunities and challenges, in Site-Specific Drug Delivery, Cell Biology, Medical and Pharmaceutical Aspects (E. Tomlinson and S. S. Davis, eds.), John Wiley Sons, Chichester, 1986, p. 27. 

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... 

A pharmacotectonics concept was illustrated by researchers, in which drug-delivery systems were arranged spatially in tissues to shape concentration fields for potent agents. NGF-releasing implants placed within 1-2 mm of the treatment site enhanced the biological function of cellular targets, whereas identical implants placed mm from the target site of treatment produced no beneficial effect (Mahoney and Saltzman, 1999). Because of some limitations with controlled delivery systems, alternatives such as encapsulation of cells that secrete these factors are discussed in the next section. 

---