Intracellular drug release

Lloyd, J.B., Duncan, R. and Pratten, M.K. (1983) Soluble synthetic polymers as targetable agents for intracellular drug release. Br. Polym. 

The phenomenon of endocytosis leads us to a second example extensive and systematic studies on endocytosis using an in vitro system (7) include the evaluation of polymers containing different peptide spacers (cf Fig. 1) which link iodotyrosine as a drug model to poly(2-hydroxypropyl-methacrylamide) (8). This study shows that by variation of peptide spacer composition the rate of intracellular drug release caused by lysosomal hydrolysis of the spacer can be controlled. 

Figure 3.22 Multiarm, water-soluble poly(organo)phosphazenes designed for a rapid, pH triggered intracellular drug release followed by a postrelease hydrolytic degradation of the carrier. Reproduced with permission from I. Teasdale, S. Wilfert,...

Warnecke et al, 2007) of DOX and MTX that are cleaved by cathepsin B. A time-dependent drug release was demonstrated in the presence of cathepsin B, and cytotoxicity studies of these conjugates against the human cell lines AsPCl LN (pancreatic carcinoma) and MDA-MB-231 LN (mamma carcinoma) revealed that the activity of the drugs was essentially retained in the conjugates, most probably owing to intracellular drug release by cathepsin B (Calderon et al, 2009). 

Sun, E, Zhou, D. and Gan, Z. (2011) Novel reduction-sensitive micelles for triggered intracellular drug release. / Control Release, 155,96-103. 

Based on these considerations, a single disulfide-linked biodegradable diblock copolymer of PGL and PEEP, named PCL-SS-PEEP (19), has been synthesized and used as a smart drug delivery carrier to accelerate intracellular drug release. The polymer forms biocompatible micelles in aqueous solution and can encapsulate the anticancer drug DOX in the PGL core. The main... 

Figure 9 Schematic illustration of the formation of cross-linked micelles and intracellular drug release. Reproduced with permission from Wang, Y. C. Li, Y. Sun, T. M. etal. Macromol. Rapid Commun. 2010, 31,1201-1206. ...

Yang, Y., Velmurugan, B., Liu, X., and Xng, B. (2013) NIR photoresponsive crosslinked upconverting nanocarriers toward selective intracellular drug release. Small, 9 (17), 2937-2944. 

Navath, R. S., Kurtoglu, Y. E., Wang, B., Kannan, S., Romero, R., and Kannan, R. M. 2008. Dendrimer-drug conjugates for tailored intracellular drug release based on glutathione levels. Bioconjug Chem 19(12), 2446-2455. 

Ryanodine receptor (RyR) is an intracellular Ca2+ release channel in the sarcoplasmic reticulum (SR) or the endoplasmic reticulum (ER). RyR binds ryanodine (a plant alkaloid, see Drugs) with a high affinity, after which it is named. 

Meyer O, et al. Cationic liposomes coated with polyethylene glycol as carriers for oligonucleotides. J Biol Chem 1998 273 15621 Shi G, et al. Efficient intracellular drug and gene delivery using folate receptor-targeted pH-sensitive liposomes composed of cationic/anionic lipid combinations. J Control Release 2002 80 309. 

Theophylline may also act as an adenosine antagonist.86 113 Adenosine is thought to bind to specific receptors on the smooth-muscle cells and to stimulate contraction. By blocking this effect, theophylline would facilitate smooth-muscle relaxation. Theophylline may likewise help produce bronchodilation by other mechanisms, such as inhibition of intracellular calcium release and stimulation of catecholamine release.115 In reality, theophylline and similar drugs may induce bronchodilation and help protect the airways through a combination of several mechanisms, but the relative importance of each cellular effect remains to be determined. 

Lee RJ et al (1998) The effects of pH and intraliposomal buffer strength on the rate of liposome content release and intracellular drug delivery. Biosci Rep 18 69-78... 

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