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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

Particle size and zeta-potential of saquinavir (SQV) nanocrystals and coarse crystals.
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fig1: Particle size and zeta-potential of saquinavir (SQV) nanocrystals and coarse crystals.

Mentions: SQV nanocrystals were prepared using an anti-solvent precipitation-high pressure homogenization method. Briefly, 400 mg of coarse SQV crystals were dissolved in 2 mL dimethyl sulfoxide (DMSO). This solution was rapidly added to 50 mL of phosphate buffered saline (PBS), pH 7.4, containing 0.12% PSS, using magnetic stirring (500 rounds per minute) to obtain a starting suspension. After anti-solvent precipitation, the suspension was placed in a high pressure homogenizer (ATS Engineering Inc, Shanghai, China) equipped with a cooling device that was connected to a circulating water bath (Julabo F12, Seelbach, Germany) and maintained at 4 °C. The homogenization occurred at 800 bars for 20 cycles, yielding a milky suspension of SQV nanocrystals as shown in Figure 1. The nanocrystal suspension was concentrated by centrifugation at 21 752×g for 30 min (Beckman Coulter Allegra 64R centrifuge, USA). The supernatant was removed, and the precipitate was dispersed in 50 mL of PBS (pH 7.4) containing 0.12% PSS.


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)

Particle size and zeta-potential of saquinavir (SQV) nanocrystals and coarse crystals.
© Copyright Policy
Related In: Results  -  Collection

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

fig1: Particle size and zeta-potential of saquinavir (SQV) nanocrystals and coarse crystals.
Mentions: SQV nanocrystals were prepared using an anti-solvent precipitation-high pressure homogenization method. Briefly, 400 mg of coarse SQV crystals were dissolved in 2 mL dimethyl sulfoxide (DMSO). This solution was rapidly added to 50 mL of phosphate buffered saline (PBS), pH 7.4, containing 0.12% PSS, using magnetic stirring (500 rounds per minute) to obtain a starting suspension. After anti-solvent precipitation, the suspension was placed in a high pressure homogenizer (ATS Engineering Inc, Shanghai, China) equipped with a cooling device that was connected to a circulating water bath (Julabo F12, Seelbach, Germany) and maintained at 4 °C. The homogenization occurred at 800 bars for 20 cycles, yielding a milky suspension of SQV nanocrystals as shown in Figure 1. The nanocrystal suspension was concentrated by centrifugation at 21 752×g for 30 min (Beckman Coulter Allegra 64R centrifuge, USA). The supernatant was removed, and the precipitate was dispersed in 50 mL of PBS (pH 7.4) containing 0.12% PSS.

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