Limits...
Enhancement of cellular uptake, transport and oral absorption of protease inhibitor saquinavir by nanocrystal formulation.

He Y, Xia DN, Li QX, Tao JS, Gan Y, Wang C - Acta Pharmacol. Sin. (2015)

Bottom Line: The dissolution, cellular uptake, and transport across a Caco-2 monolayer of the nanocrystal formulation were significantly improved compared to those of the coarse crystals.Pharmacokinetic study showed that the maximal plasma concentration (Cmax) was 2.16-fold of that for coarse crystalline SQV suspension, whereas the area under the curve (AUC) of nanocrystal SQV suspension was 1.95-fold of that for coarse crystalline SQV suspension.The nanocrystal drug delivery system significantly improves the oral absorption of saquinavir.

View Article: PubMed Central - PubMed

Affiliation: School of Pharmacy, Chongqing Medical University, Chongqing 400016, China.

ABSTRACT

Aim: Saquinavir (SQV) is the first protease inhibitor for the treatment of HIV infection, but with poor solubility. The aim of this study was to prepare a colloidal nanocrystal suspension for improving the oral absorption of SQV.

Methods: SQV nanocrystals were prepared using anti-solvent precipitation-high pressure homogenization method. The nanocrystals were characterized by a Zetasizer and transmission electron microscopy (TEM). Their dissolution, cellular uptake and transport across the human colorectal adenocarcinoma cell line (Caco-2) monolayer were investigated. Bioimaging of ex vivo intestinal sections of rats was conducted with confocal laser scanning microscopy. Pharmacokinetic analysis was performed in rats administered nanocrystal SQV suspension (50 mg/kg, ig), and the plasma SQV concentrations were measured with HPLC.

Results: The SQV nanocrystals were approximately 200 nm in diameter, with a uniform size distribution. The nanocrystals had a rod-like shape under TEM. The dissolution, cellular uptake, and transport across a Caco-2 monolayer of the nanocrystal formulation were significantly improved compared to those of the coarse crystals. The ex vivo intestinal section study revealed that the fluorescently labeled nanocrystals were located in the lamina propria and the epithelium of the duodenum and jejunum. Pharmacokinetic study showed that the maximal plasma concentration (Cmax) was 2.16-fold of that for coarse crystalline SQV suspension, whereas the area under the curve (AUC) of nanocrystal SQV suspension was 1.95-fold of that for coarse crystalline SQV suspension.

Conclusion: The nanocrystal drug delivery system significantly improves the oral absorption of saquinavir.

No MeSH data available.


Related in: MedlinePlus

Histological examination of the absorption of saquinavir (SQV) nanocrystals and coarse crystals in the intestinal mucosa 1 h after oral administration. The figures in the right column are the magnified images of white rectangular regions on the left. Lamina propria (LP), intestinal epithelium cells (EC).
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4561971&req=5

fig7: Histological examination of the absorption of saquinavir (SQV) nanocrystals and coarse crystals in the intestinal mucosa 1 h after oral administration. The figures in the right column are the magnified images of white rectangular regions on the left. Lamina propria (LP), intestinal epithelium cells (EC).

Mentions: To study the uptake of SQV nanocrystals in intestinal tract, the nanocrystals were labeled with ethyl rhodamine B, and the intestinal mucosal absorption was studied by CLSM. Figure 7 shows the representative CLSM images of different intestinal segments (duodenum, jejunum, and ileum) at 1 h after oral administration of fluorescein labeled SQV nanocrystals and coarse SQV crystals. The crystals in the intestinal lumen were removed by extensive washing with large amounts of cold saline. The red fluorescent signals observed indicate the nanocrystals or diffuse fluorescein uptake by the intestinal epithelia cells.


Enhancement of cellular uptake, transport and oral absorption of protease inhibitor saquinavir by nanocrystal formulation.

He Y, Xia DN, Li QX, Tao JS, Gan Y, Wang C - Acta Pharmacol. Sin. (2015)

Histological examination of the absorption of saquinavir (SQV) nanocrystals and coarse crystals in the intestinal mucosa 1 h after oral administration. The figures in the right column are the magnified images of white rectangular regions on the left. Lamina propria (LP), intestinal epithelium cells (EC).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4561971&req=5

fig7: Histological examination of the absorption of saquinavir (SQV) nanocrystals and coarse crystals in the intestinal mucosa 1 h after oral administration. The figures in the right column are the magnified images of white rectangular regions on the left. Lamina propria (LP), intestinal epithelium cells (EC).
Mentions: To study the uptake of SQV nanocrystals in intestinal tract, the nanocrystals were labeled with ethyl rhodamine B, and the intestinal mucosal absorption was studied by CLSM. Figure 7 shows the representative CLSM images of different intestinal segments (duodenum, jejunum, and ileum) at 1 h after oral administration of fluorescein labeled SQV nanocrystals and coarse SQV crystals. The crystals in the intestinal lumen were removed by extensive washing with large amounts of cold saline. The red fluorescent signals observed indicate the nanocrystals or diffuse fluorescein uptake by the intestinal epithelia cells.

Bottom Line: The dissolution, cellular uptake, and transport across a Caco-2 monolayer of the nanocrystal formulation were significantly improved compared to those of the coarse crystals.Pharmacokinetic study showed that the maximal plasma concentration (Cmax) was 2.16-fold of that for coarse crystalline SQV suspension, whereas the area under the curve (AUC) of nanocrystal SQV suspension was 1.95-fold of that for coarse crystalline SQV suspension.The nanocrystal drug delivery system significantly improves the oral absorption of saquinavir.

View Article: PubMed Central - PubMed

Affiliation: School of Pharmacy, Chongqing Medical University, Chongqing 400016, China.

ABSTRACT

Aim: Saquinavir (SQV) is the first protease inhibitor for the treatment of HIV infection, but with poor solubility. The aim of this study was to prepare a colloidal nanocrystal suspension for improving the oral absorption of SQV.

Methods: SQV nanocrystals were prepared using anti-solvent precipitation-high pressure homogenization method. The nanocrystals were characterized by a Zetasizer and transmission electron microscopy (TEM). Their dissolution, cellular uptake and transport across the human colorectal adenocarcinoma cell line (Caco-2) monolayer were investigated. Bioimaging of ex vivo intestinal sections of rats was conducted with confocal laser scanning microscopy. Pharmacokinetic analysis was performed in rats administered nanocrystal SQV suspension (50 mg/kg, ig), and the plasma SQV concentrations were measured with HPLC.

Results: The SQV nanocrystals were approximately 200 nm in diameter, with a uniform size distribution. The nanocrystals had a rod-like shape under TEM. The dissolution, cellular uptake, and transport across a Caco-2 monolayer of the nanocrystal formulation were significantly improved compared to those of the coarse crystals. The ex vivo intestinal section study revealed that the fluorescently labeled nanocrystals were located in the lamina propria and the epithelium of the duodenum and jejunum. Pharmacokinetic study showed that the maximal plasma concentration (Cmax) was 2.16-fold of that for coarse crystalline SQV suspension, whereas the area under the curve (AUC) of nanocrystal SQV suspension was 1.95-fold of that for coarse crystalline SQV suspension.

Conclusion: The nanocrystal drug delivery system significantly improves the oral absorption of saquinavir.

No MeSH data available.


Related in: MedlinePlus