Drug release triggers

Type of system Design principle Reservoir drugs Drug release triggering agent Reference... 

Figure 6 (a) Schematic presentation of polymeric nanoparticles with weak acid (sulfonamide groups). The polymeric nanoparticles show good stabdity at pH 7.4 but are aggregated/shrunken near the tumor where the pH is below tumor pHg. (b) A schematic concept of anticancer drug release triggered by the change of hydrophobic core solubility in the polymeric micelle. 

In the pharmaceutics literature, an application-triggered drug release from an O/W emulsion recipe has been reported. The application of emulsions in the pharmaceutical industry is very important, and a large number of references are found in the current literature. 

Kong, G., Anyarambhatla, G., Petros, W.P, et al. Efficacy of liposomes and hyperthermia in a human tumor xenograft model Importance of triggered drug release. Cancer Res. 60(24) 6950-6957. 2000. 

Open-looped systems operate on trigger signals sent from an external device that thereby activates the implanted system and causes drug release within the body. Pulse delivery occurs by magnetic, ultrasonic, or electronic means in open-looped systems. 

Pumps are intended for implantation. An osmotic pressure differential triggers drug release from a reservoir embraced by a semipermeable membrane [26]. 

Bio-responsive release the system modulates drug release in response to a biological stimulus (e.g. blood glucose levels triggering the release of insulin from a dmg delivery device). 

Babincova, M., Sourivong, P., Chorvat, D., and Babinec, P. (1999), Laser triggered drug release from magnetoliposomes,/. Magnetism Magnetic Mater., 194,163-166. 

Scheme 5.6 Glutathione-triggered cascade drug release for tumor-targeting of fluoro-taxoid conjugates.

This would support the fact that PEG-HZ-PE conjugates containing hydrazone bond derived from the aliphatic aldehyde are more prone to hydrolytic degradation. Aromatic aldehyde-derived hydrazone bond is too stable for the purpose of pH-triggered drug release. Careful selection of an aldehyde and an acyl hydrazide would be necessary for the application of the hydrazone-based chemistry for the development of pH-sensitive pharmaceutical nanocarriers. 

The acidification of endosomal compartments, as they evolve toward lysosomes is a well-described phenomenon (1) that can be exploited to design drug delivery systems capable of releasing their contents after endocytosis. Enhanced cytoplasmic drug concentrations can therefore be achieved with smart formulations, which are sensitive to acidic pHs. For this purpose, liposomal formulations are attractive, because their deformable phospholipid bilayers can be rapidly disrupted to trigger drug release. In this section, ionizable copolymers of ISTisopropylacrylamide (NIPAM) are anchored in the phospholipid membrane and used to destabilize the bilayer upon acidification of the environment. 

This chapter thoroughly describes the preparation of poly(NIPAM-co-MAA)-based liposomes that can enhance the cytoplasmic bioavailability of drugs by triggering drug release, specifically, in acidic compartments. The optimization and characterization of these systems have been described in numerous publications (3-9). 

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