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. 2018 Dec 4;19(1):79.
doi: 10.1186/s40360-018-0275-5.

Enhancement of saquinavir absorption and accumulation through the formation of solid drug nanoparticles

Gabriel Kigen  1   2 , Geoffrey Edwards  3
Affiliations

Enhancement of saquinavir absorption and accumulation through the formation of solid drug nanoparticles

Gabriel Kigen et al. BMC Pharmacol Toxicol. .

Abstract

Background: Nanotechnology is now considered a promising drug delivery method for orally administered hydrophobic drugs to their sites of action. The effect of nanodispersion on cellular transport and accumulation of saquinavir (SQV) was investigated.

Methods: The transport of five solid drug nanoparticle (SDN) SQV formulations along Caco-2 cell monolayers (CCM) was compared to that of standard SQV. The SDNs were prepared using SQV mesylate (20%), Pluronic F127 (10%) plus five other excipients (HPMC, PVP, PVA, Lecithin S75 and Span 80) in different proportions. Cellular accumulation in CEM parental and CEMVBL (P-gp overexpressing) cells was conducted to ascertain the effect of nanodispersion on P-gp mediated efflux of SQV. All SDN formulations were dissolved in water, whereas SQV in DMSO to improve solubility. Quantification was via HPLC.

Results: From transport results, an SDN sample composed of SQV mesylate/Pluronic F127 plus HPMC (70%) and had a 24% increase in apparent absorption compared to standard SQV, largely driven by a 38% reduction in basolateral to apical permeation. Additionally, the formulation and two others (SQV mesylate/Pluronic F127 alone; and + HPMC (65%)/Lecithin [5%]) accumulated more significantly in CEM cells, suggesting enhanced delivery to these cells. Moreover, accumulation and transport of the three SDNs compared well to that of SQV despite being dissolved in water, suggestive of improved dissolution. The inclusion of PVA resulted in increased efflux.

Conclusion: The use of HPMC and Pluronic F127 produced SQV SDNs with improved permeation in Caco-2 cells and improved accumulation in CEM cells, but negative effects with PVA.

Keywords: Caco-2 cell monolayers; Saquinavir; accumulation; nanodispersion; solid drug nanoparticles; transport.

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Figures

Fig. 1
Fig. 1
Apparent absorption of standard SQV and five SQV SDNs across the differentiated Caco-2 monolayers after 1 hour of incubation (n=5)
Fig. 2
Fig. 2
Apparent permeability of standard SQV and five SQV SDNs across the differentiated Caco-2 monolayers after 1 hour of incubation (n=5)
Fig. 3
Fig. 3
Cellular accumulation ratios [CAR] (Mean ± SD, n=5), * p <0.05, ** p <0.01
See this image and copyright information in PMC

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References

    1. Fletcher CV, Staskus K, Wietgrefe SW, Rothenberger M, Reilly C, Chipman JG, Beilman GJ, Khoruts A, Thorkelson A, Schmidt TE, et al. Persistent HIV-1 replication is associated with lower antiretroviral drug concentrations in lymphatic tissues. Proceedings of the National Academy of Sciences of the United States of America. 2014;111:2307–2312. doi: 10.1073/pnas.1318249111. - DOI - PMC - PubMed
    1. Kumar A, Abbas W, Herbein G. HIV-1 latency in monocytes/macrophages. Viruses. 2014;6:1837–1860. doi: 10.3390/v6041837. - DOI - PMC - PubMed
    1. Curley Paul, Liptrott Neill J, Owen Andrew. Advances in nanomedicine drug delivery applications for HIV therapy. Future Science OA. 2018;4(1):FSO230. doi: 10.4155/fsoa-2017-0069. - DOI - PMC - PubMed
    1. Choi JY, Thapa RK, Yong CS, Kim JO. Nanoparticle-based combination drug delivery systems for synergistic cancer treatment. Journal of Pharmaceutical Investigation. 2016;46:325–339. doi: 10.1007/s40005-016-0252-1. - DOI
    1. Dizaj SM, Vazifehasl Z, Salatin S, Adibkia K, Javadzadeh Y. Nanosizing of drugs: Effect on dissolution rate. Research in pharmaceutical sciences. 2015;10:95–108. - PMC - PubMed

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