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

Dissolution profiles of saquinavir (SQV) and ethyl rhodamine B (RHD) from nanocrystals and coarse crystals (n=3).
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4561971&req=5

fig4: Dissolution profiles of saquinavir (SQV) and ethyl rhodamine B (RHD) from nanocrystals and coarse crystals (n=3).

Mentions: The solubility of the nanocrystals in PBS (pH 6.8) was 40.85±11.36 μg/mL, which was lower than the solubility of the coarse powder 72.61±17.86 μg/mL. This difference in solubility was most likely because, while the coarse drug powder was in the mesylate salt form, the drug could have been converted to the free base during the preparation of the nanocrystal formulation. The dissolution profiles of the nanocrystals and the coarse crystals are shown in Figure 4. Only 20% of the coarse crystals were dissolved during a 2 h test period, while approximately 60% dissolution was observed for the SQV nanocrystals. A state of equilibrium was achieved in 30 min. The results demonstrate that the dissolution rate of the SQV nanocrystals is faster than the coarse powder. The promising results of the drug release studies prompted cellular and in vivo studies in rats with the nanocrystal formulation.


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)

Dissolution profiles of saquinavir (SQV) and ethyl rhodamine B (RHD) from nanocrystals and coarse crystals (n=3).
© Copyright Policy
Related In: Results  -  Collection

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

fig4: Dissolution profiles of saquinavir (SQV) and ethyl rhodamine B (RHD) from nanocrystals and coarse crystals (n=3).
Mentions: The solubility of the nanocrystals in PBS (pH 6.8) was 40.85±11.36 μg/mL, which was lower than the solubility of the coarse powder 72.61±17.86 μg/mL. This difference in solubility was most likely because, while the coarse drug powder was in the mesylate salt form, the drug could have been converted to the free base during the preparation of the nanocrystal formulation. The dissolution profiles of the nanocrystals and the coarse crystals are shown in Figure 4. Only 20% of the coarse crystals were dissolved during a 2 h test period, while approximately 60% dissolution was observed for the SQV nanocrystals. A state of equilibrium was achieved in 30 min. The results demonstrate that the dissolution rate of the SQV nanocrystals is faster than the coarse powder. The promising results of the drug release studies prompted cellular and in vivo studies in rats with the nanocrystal formulation.

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