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Mechanism of enhanced oral absorption of hydrophilic drug incorporated in hydrophobic nanoparticles.

Lv LZ, Tong CQ, Yu J, Han M, Gao JQ - Int J Nanomedicine (2013)

Bottom Line: Hydroxysafflor yellow A (HSYA) is an effective ingredient of the Chinese herb Carthamus tinctorius L, which has high water solubility and low oral bioavailability.This research aims to develop a hydrophobic nanoparticle that can enhance the oral absorption of HSYA.Both enhanced uptake in Caco-2 cells monolayer and increased bioavailability in rats for HSYA nanoparticles indicated that the formulation could improve bioavailability of HSYA significantly after oral administration both in vitro and in vivo.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacy, Zhejiang Provincial People's Hospital, Hangzhou, People's Republic of China.

ABSTRACT
Hydroxysafflor yellow A (HSYA) is an effective ingredient of the Chinese herb Carthamus tinctorius L, which has high water solubility and low oral bioavailability. This research aims to develop a hydrophobic nanoparticle that can enhance the oral absorption of HSYA. Transmission electron microscopy and freeze-fracture replication transmission election microscopy showed that the HSYA nanoparticles have an irregular shape and a narrow size distribution. Zonula occludens 1 protein (ZO-1) labeling showed that the nanoparticles with different dilutions produced an opening in the tight junctions of Caco-2 cells without inducing cytotoxicity to the cells. Both enhanced uptake in Caco-2 cells monolayer and increased bioavailability in rats for HSYA nanoparticles indicated that the formulation could improve bioavailability of HSYA significantly after oral administration both in vitro and in vivo.

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Related in: MedlinePlus

HSYA release from nanoparticles in double-distilled water at 4°C (n = 3).Note:Figure 2B is an enlarged version of Figure 2A.Abbreviations: HSYA, hydroxysafflor yellow A; NP, nanoparticle.
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f2-ijn-8-2709: HSYA release from nanoparticles in double-distilled water at 4°C (n = 3).Note:Figure 2B is an enlarged version of Figure 2A.Abbreviations: HSYA, hydroxysafflor yellow A; NP, nanoparticle.

Mentions: In this study, we developed a hydrophobic nanoparticle oil solution, the novel formulation of which could be a nanocarrier for hydrophilic drugs with the drug dispersed in the oil phase. Actually, a clear and transparent nanoparticles oil solution was formed when organic solutions A and B were mixed, which means HSYA could be dissolved in organic solvent with soybean phospholipids. After the evaporation of organic solvent, the nanoparticles of HSYA/ soybean phospholipids dispersed in GTCC were formed with the structure of a hydrophilic core and hydrophobic surface. As a water soluble drug, HSYA was wrapped in the core of nanoparticles. No deposition could be observed. The formulation composition and preparation process in the present study was determined after some experimental optimization, as not all kinds of oil and surfactant could form the nanoparticles of “hydrophilic drug dispersed in hydrophobic oil”. Due to its pure anhydrous environment, the nanoparticle was more stable for HSYA when compared to SDEDDS. From the pharmacokinetic results (Figure 6 and Table 1), we can see that the nanoparticles increased the absolute bioavailability and relative bioavailability to 23.6- and 23.3-fold, respectively. Figure 1 shows that the nanoparticles exhibited an irregular structure, with a particle size of 49.2 nm ± 5.8 nm. The polydispersity of HSYA nanoparticles was 0.38, which indicated that the particle size distribution of nanoparticles is relatively non-uniform. In the future, we will optimize the prescription of nanoparticles in order to get uniform size, and to shape rounded particles. In this article, the reversed-dialysis bag method was applied to the in vitro release studies,23 and sustained in vitro release was achieved (Figure 2). However, the nanoparticles did not exhibit a sustained release effect in vivo. We speculate that there are significant differences between in vivo and in vitro environments.


Mechanism of enhanced oral absorption of hydrophilic drug incorporated in hydrophobic nanoparticles.

Lv LZ, Tong CQ, Yu J, Han M, Gao JQ - Int J Nanomedicine (2013)

HSYA release from nanoparticles in double-distilled water at 4°C (n = 3).Note:Figure 2B is an enlarged version of Figure 2A.Abbreviations: HSYA, hydroxysafflor yellow A; NP, nanoparticle.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3735274&req=5

f2-ijn-8-2709: HSYA release from nanoparticles in double-distilled water at 4°C (n = 3).Note:Figure 2B is an enlarged version of Figure 2A.Abbreviations: HSYA, hydroxysafflor yellow A; NP, nanoparticle.
Mentions: In this study, we developed a hydrophobic nanoparticle oil solution, the novel formulation of which could be a nanocarrier for hydrophilic drugs with the drug dispersed in the oil phase. Actually, a clear and transparent nanoparticles oil solution was formed when organic solutions A and B were mixed, which means HSYA could be dissolved in organic solvent with soybean phospholipids. After the evaporation of organic solvent, the nanoparticles of HSYA/ soybean phospholipids dispersed in GTCC were formed with the structure of a hydrophilic core and hydrophobic surface. As a water soluble drug, HSYA was wrapped in the core of nanoparticles. No deposition could be observed. The formulation composition and preparation process in the present study was determined after some experimental optimization, as not all kinds of oil and surfactant could form the nanoparticles of “hydrophilic drug dispersed in hydrophobic oil”. Due to its pure anhydrous environment, the nanoparticle was more stable for HSYA when compared to SDEDDS. From the pharmacokinetic results (Figure 6 and Table 1), we can see that the nanoparticles increased the absolute bioavailability and relative bioavailability to 23.6- and 23.3-fold, respectively. Figure 1 shows that the nanoparticles exhibited an irregular structure, with a particle size of 49.2 nm ± 5.8 nm. The polydispersity of HSYA nanoparticles was 0.38, which indicated that the particle size distribution of nanoparticles is relatively non-uniform. In the future, we will optimize the prescription of nanoparticles in order to get uniform size, and to shape rounded particles. In this article, the reversed-dialysis bag method was applied to the in vitro release studies,23 and sustained in vitro release was achieved (Figure 2). However, the nanoparticles did not exhibit a sustained release effect in vivo. We speculate that there are significant differences between in vivo and in vitro environments.

Bottom Line: Hydroxysafflor yellow A (HSYA) is an effective ingredient of the Chinese herb Carthamus tinctorius L, which has high water solubility and low oral bioavailability.This research aims to develop a hydrophobic nanoparticle that can enhance the oral absorption of HSYA.Both enhanced uptake in Caco-2 cells monolayer and increased bioavailability in rats for HSYA nanoparticles indicated that the formulation could improve bioavailability of HSYA significantly after oral administration both in vitro and in vivo.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacy, Zhejiang Provincial People's Hospital, Hangzhou, People's Republic of China.

ABSTRACT
Hydroxysafflor yellow A (HSYA) is an effective ingredient of the Chinese herb Carthamus tinctorius L, which has high water solubility and low oral bioavailability. This research aims to develop a hydrophobic nanoparticle that can enhance the oral absorption of HSYA. Transmission electron microscopy and freeze-fracture replication transmission election microscopy showed that the HSYA nanoparticles have an irregular shape and a narrow size distribution. Zonula occludens 1 protein (ZO-1) labeling showed that the nanoparticles with different dilutions produced an opening in the tight junctions of Caco-2 cells without inducing cytotoxicity to the cells. Both enhanced uptake in Caco-2 cells monolayer and increased bioavailability in rats for HSYA nanoparticles indicated that the formulation could improve bioavailability of HSYA significantly after oral administration both in vitro and in vivo.

Show MeSH
Related in: MedlinePlus