PH sensitive systems

Devalapally H, Shenoy D, Little S, Langer R, Amiji M (2007) Polyethylene oxide)-modified poly(beta-amino ester) nanoparticles as a pH-sensitive system for tumor-targeted delivery of... 

With the aim to reduce unspecific protein interactions while controlling DNA release, acid-sensitive PEG has been designed. Several pH-sensitive systems are described in Volume I, Chapter 8. Briefly, the objective is to develop molecules for biological purposes, which means molecules able to be destabilized at slight pH changes. Tumors or ischemia sites present... 

Devalapally, H., Shenoy, D., Little, S., Langer, R., and Amiji, M. (2007), Poly(ethylene oxide)-modified poly(beta-amino ester) nanoparticles as a pH-sensitive system for tumor-targeted delivery of hydrophobic drugs Part 3. Therapeutic efficacy and safety studies in ovarian cancer xenograft model, Cancer Chemother. Pharmacol., 59(4), 477-484. 

More information on how to handle such pH sensitive systems is available elsewhere [31]. 

Recently, there have been various attempts to develop responsive systems for release to specific signals. For example, thermoresponsive polymeric carriers that respond to hyperthermic conditions [108] and pH-sensitive systems that activate in tumor-acidic pHs [109] have been investigated. 

Normally the water-soluble drug is added during the hydration process and subsequently the loaded polymersomes are purified by the original solution by either dialysis or size exclusion chromatography [68]. However, this method ensures relative high encapsulation efficiency only if combined with post processing by extrusion or sonication [51,112]. Interaction between copolymers and the desired molecules certainly favours the efficiency. pH sensitive systems such as PMPC-PDPA showed efficient encapsulation efficiency due to the strong interaction between the polymers and the DNA prior to pH variation [51,70,113]. 

Among the controlled drug delivery systems, pH-sensitive system has a special interest in view of the fact that both extracellular tumor (pH 6.8) and endosomes (pH 5.5) are more acidic than normal tissues (pH 7.4). The physical stimuli, such as temperature, or magnetic field will affect the level of various energy sources and alter molecular interactions at critical points. Treating the synthesized microspheres under the above environments can affect their behavior via the interactions of the polymeric chains. 

The text is kept as pedagogical and as simple as possible, and the literature review is not exhaustive, particularly on theoretical aspects, but rather selective of important fundamental developments, historical milestones, and technological breakthroughs. The scope is limited by editorial choice to systems containing ionic surfactants and some ionic-nonionic mixtures such as those involving pH-sensitive systems. 

Such pH-sensitive systems are best treated as containing a mixture of two amphiphilic species that occur in different proportions depending on the pH. For instance, the fatty acid-fatty soap equilibrium in water [82] can be expressed as... 

Another kind of difficulty arises with pH-sensitive systems containing both an aqueous phase and an oil phase. It is due to the fact that the dissociated (ionic) and undissociated (nonionic) species are likely to selectively partition or fractionate between water and oil. As shown in Fig. 15, it can generally be assumed that the amount of dissociated salt in oil [Ac ] is negligible, whereas the amount of undissociated acid in water [AcH ,] is to be taken into account since it appears in the dissociation equilibrium [84,85]. 

Cui, L., Cohen, J.A., Broaders, K.E., Beaudette, T.T., Frechet, J.M. Mannosylated dextran nanoparticles a pH-sensitive system engineered for immunomodulation through mannose targeting. Bioconjug. Chem. 22, 949-957 (2011)... 

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