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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

Morphology of coarse saquinavir (SQV) crystals (A) and SQV nanocrystals (B) observed under a scanning electron microscope and transmission electron microscope, respectively; Fluorescent-labeled coarse SQV crystals (C) and nanocrystals (D), as observed under a confocal laser scanning microscope.
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fig2: Morphology of coarse saquinavir (SQV) crystals (A) and SQV nanocrystals (B) observed under a scanning electron microscope and transmission electron microscope, respectively; Fluorescent-labeled coarse SQV crystals (C) and nanocrystals (D), as observed under a confocal laser scanning microscope.

Mentions: The particle morphology of the coarse powder was examined under an SEM. The coarse powder presented an irregular shape and a particle size of approximately 2–5 μm, as shown in Figure 2A. By contrast, the examination of the nanocrystals by TEM revealed rod-shaped particles, as shown in Figure 2B. The length of the nanocrystals measured by TEM was in agreement with the particle size measured by the Zetasizer.


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)

Morphology of coarse saquinavir (SQV) crystals (A) and SQV nanocrystals (B) observed under a scanning electron microscope and transmission electron microscope, respectively; Fluorescent-labeled coarse SQV crystals (C) and nanocrystals (D), as observed under a confocal laser scanning microscope.
© Copyright Policy
Related In: Results  -  Collection

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

fig2: Morphology of coarse saquinavir (SQV) crystals (A) and SQV nanocrystals (B) observed under a scanning electron microscope and transmission electron microscope, respectively; Fluorescent-labeled coarse SQV crystals (C) and nanocrystals (D), as observed under a confocal laser scanning microscope.
Mentions: The particle morphology of the coarse powder was examined under an SEM. The coarse powder presented an irregular shape and a particle size of approximately 2–5 μm, as shown in Figure 2A. By contrast, the examination of the nanocrystals by TEM revealed rod-shaped particles, as shown in Figure 2B. The length of the nanocrystals measured by TEM was in agreement with the particle size measured by the Zetasizer.

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