In vivo evaluation of thiolated poly(acrylic acid) as a drug absorption modulator for MRP2 efflux pump substrates

Influence of excipients on drug absorption via modulation of intestinal transporters activity

“…Thiolated poly acrylic acid has the benefit of high molecular mass and remains unabsorbed from the intestine and thus excludes systemic side effects. [2] Chitosan is a widely explored excipient due to its biocompatibility and biodegradability and its thiolated form thus incorporates all its advantages. Various grades of eudragit are used as film coating agents.…”

“…Absorption was more from gut where, sulforhodamine 101 does not get absorbed in absence of thiolated PAA 250 (it gets absorbed only in stomach), thus indicating inhibitory action of MRP2 since expression of MRP2 is reported to be highest in duodenum epithelium and absent in stomach epithelium. [2] Thiolated chitosan derivatives Chitosan is known for its widespread use in design of drug delivery systems. Various derivatives of chitosan have been developed to modify its properties.…”

“…Carrier mediated transport, on the other hand, depends on transport proteins and is either energy dependent or independent. [1][2][3] Various such transport proteins are discovered that affects the absorption of many drugs and their metabolites through the intestinal barrier, blood brain barrier, and other organs like liver and kidney. These transport proteins include P-glycoprotein (P-gp), multi-drug resistant protein, oligo-peptide transporter and others.…”

Preactivated thiomers: Permeation enhancing properties

“…Thiolated polymers or thiomers are a group of polymers bearing thiol substructures. Due to the immobilization of thiol groups on already well-established polymeric excipients such as polyacrylates (Leitner et al, 2003; Hombach et al, 2009; Bernkop-Schnürch and Thaler, 2000a; Kast et al, 2003) or chitosans (Sakloetsakun et al, 2009; Hombach et al, 2009; Jin et al, 2011; Li et al, 2011), features such as mucoadhesive (Hombach et al, 2009; Bernkop-Schnürch et al, 1999), in situ gelling (Sakloetsakun et al, 2009), efflux pump inhibiting (Greindl et al, 2009) and permeation enhancing properties (Kast et al, 2003; Hombach et al, 2008) are strongly improved. However, there are also shortcomings of thiomers, in particular regarding storage stability.…”

In vivo investigation of thiomer–polyvinylpyrrolidon nanoparticles using magnetic resonance imaging

“…For our purpose, nanoparticles were synthesized on the basis of the well‐characterized and strongly permeation enhancing polymer, polyacrylic acid–cysteine (PAA–Cys) 6, 7. Besides the permeation enhancing properties of PAA–Cys, the thiolated polymer is able to reduce enzymatic degradation8, 9 and exhibits strong mucoadhesive properties 10–12.…”