A Novel Nanocapsule Delivery System to Overcome Intestinal Degradation and Drug Transport Limited Absorption of P-glycoprotein Substrate Drugs

Abstract

The overall results suggest that the novel nanodelivery system which does not alter the activity of the P-gp is a potential platform for intestinal transport of sensitive lipophilic molecules that are P-gp substrates.

Physicochemical characterization of tacrolimus-loaded solid dispersion with sodium carboxylmethyl cellulose and sodium lauryl sulfate

“…The mobile phase was consisted of water, acetonitrile and isopropanol (7/2/1, volume ratio). The eluent was monitored at 210 nm with a flow rate of 0.4 mL/min (Borhade et al, 2008;Miao etal., 2008;Moyano et al, 2006;Nassar et al, 2008;Patil et al, 2008).…”

“…About 2 mg of samples were placed in sealed aluminum pans, before heating under nitrogen flow (25 mL/min) at a heating rate of 10 o C/min from 30 to 215 o C. Furthermore, the crystallinity of powder, carriers and solid dispersions were assessed by powder X-ray diffraction (D/MAX-2500, Rigacu, Japan) conducted at room temperature using monochromatic Cu K α -radiation (λ=1.54178 Å) at 40 mA and 40 kV in the region of 2.5 o ≤ 2θ ≤ 40 o with an angular increment of 0.02º per second (Nassar et al, 2008;Sinswat et al, 2008).…”

“…It is a poorly water-soluble compound which gave the low aqueous solubility of about 1-2 µg/mL (Hane et al, 1992;Honbo et al, 1987;Tamura et al, 2002). Various oral formulations of tacrolimus such as inclusion complex (Arima et al, 2001), nanoparticle (Nassar et al, 2008;Sinswat et al, 2008), Prodrug with poly (ethylene glycol) esters (Chung and Cho, 2004), liposome (Lee et al, 1995), microemulsion (Borhade et al, 2008a;2008b) and solid dispersion (Yamashita et al, 2003) were developed to improve the solubility of tacrolimus.…”

Design, Characterization, and In Vivo Pharmacokinetics of Tacrolimus Proliposomes

“…Most of these techniques have been focused on improving the solubility and absorption of tacrolimus from the GI tract or reducing P-gp efflux and CYP-450-mediated metabolism, with limited success. The reported approaches include prodrug (21), cyclodextrin complexes (22), solid dispersions (23,24), liposomes (25), self-microemulsifying drug delivery system (26)(27)(28), nanocapsules (29), micelles (30), nanosomes (31), microspheres (32), and nanoliposomes of dry powder inhaler (33). However, these investigational findings have not effectively translated into human clinical trials except solid dispersions.…”

In vitro and in vivo studies of lipid-based nanocarriers for oral N3-o-toluyl-fluorouracil delivery

“…As one of the pro-drugs of 5-fluorouracil (5-Fu), TFu could be selectively metabolized to 5-Fu in the tumor tissue due to the higher level of amidase activity in the tumor cells. However, the harsh conditions of the gastrointestinal tract and the limited permeability across the intestinal barrier makes the situation very complex and, hence, the clinical application of TFu is greatly restricted by the low bioavailability after oral administration (Norris et al, 1998;Szakács et al, 2001;Nassar et al, 2008).…”