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Improved oral bioavailability and brain transport of Saquinavir upon administration in novel nanoemulsion formulations
Open accessAbstract
The aim of this investigation was to develop novel oil-in-water (o/w) nanoemulsions containing Saquinavir (SQV), an anti-HIV protease inhibitor, for enhanced oral bioavailability and brain disposition. SQV was dissolved in different types of edible oils rich in essential polyunsaturated fatty acids (PUFA) to constitute the internal oil phase of the nanoemulsions. The external phase consisted of surfactants Lipoid-80 and deoxycholic acid dissolved in water. The nanoemulsions with an average oil droplet size of 100-200 nm, containing tritiated [(3)H]-SQV, were administered orally and intravenously to male Balb/c mice. The SQV bioavailability as well as distribution in different organ systems was examined. SQV concentrations in the systemic circulation administered in flax-seed oil nanoemulsions were threefold higher as compared to the control aqueous suspension. The oral bioavailability and distribution to the brain, a potential sanctuary site for HIV, were significantly enhanced with SQV delivered in nanoemulsion formulations. In comparing SQV in flax-seed oil nanoemulsion with aqueous suspension, the maximum concentration (C(max)) and the area-under-the-curve (AUC) values were found to be five- and threefold higher in the brain, respectively, suggesting enhanced rate and extent of SQV absorption following oral administration of nanoemulsions. The results of this study show that oil-in-water nanoemulsions made with PUFA-rich oils may be very promising for HIV/AIDS therapy, in particular, for reducing the viral load in important anatomical reservoir sites.
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“Lecithin (phosphatidylcholine) [36], sodium deoxycholate (bile salt) [37], polyoxyethlene sorbitan monolaurate (Tween 20, 40, 60, 80) [38] and sorbitan monolaurate (Span 20, 40, 60, 80) [39] are commonly employed in the preparation of NEs. Other surfactants proposed are poloxamers [40], sodium dodecyl sulfate [41], amphiphilic proteins like casein [42], polysaccharides (starch derivatives, gums) [”
From Nanoemulsions for “Nose-to-Brain” Drug Delivery (2019) · cites this paper as [37]
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Nanoemulsions in CNS drug delivery: recent developments, impacts and challenges
Karami, Z., Zanjani, M. R. S., & Hamidi, M. (2019) · Drug Discovery Today · doi:10.1016/j.drudis.2019.03.021 · Cited by 102
Evaluation of chitosan nanoformulations as potent anti-HIV therapeutic systems
Ramana, L. N., Sharma, S., Sethuraman, S., Ranga, U., & Krishnan, U. M. (2013) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2013.10.002 · Cited by 83
“Oil in water emulsions of saquinavir were found to exhibit superior oral bioavailability [18].”
BackgroundYadav, S., Gattacceca, F., Panicucci, R., & Amiji, M. M. (2015) · Molecular Pharmaceutics · doi:10.1021/mp5008376 · Cited by 76
Self-citationGonçalves, A., Nikmaram, N., Roohinejad, S., Estevinho, B. N., Rocha, F. A., Greiner, R., & McClements, D. J. (2017) · Colloids and Surfaces A Physicochemical and Engineering Aspects · doi:10.1016/j.colsurfa.2017.10.076 · Cited by 98
Cao, X., Luo, J.-W., Gong, T., Zhang, Z.-R., Sun, X., & Fu, Y. (2015) · Molecular Pharmaceutics · doi:10.1021/mp500637b · Cited by 72
Shinde, R. L., Bharkad, G. P., & Devarajan, P. V. (2015) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/j.ejpb.2015.08.008 · Cited by 72
Sarmento, B., Gomes, M. J., & das Neves, J. (2014) · International Journal of Nanomedicine · doi:10.2147/ijn.s45886 · Cited by 70
Parthasarathy, S., Tang, S., & Manickam, S. (2013) · doi:10.1021/ie4008858 · Cited by 70
Preclinical Formulations: Insight, Strategies, and Practical Considerations
Shah, S. M., Jain, A. S., Kaushik, R., Nagarsenker, M. S., & Nerurkar, M. J. (2014) · AAPS PharmSciTech · doi:10.1208/s12249-014-0156-1 · Cited by 80
Towards nanomedicines for neuroAIDS
Sagar, V., Pilakka‐Kanthikeel, S., Pottathil, R., Saxena, S. K., & Nair, M. (2014) · Reviews in Medical Virology · doi:10.1002/rmv.1778 · Cited by 71
“[93] demonstrated that the oral administration of saquinavir loaded oil-in-water nanoemulsions to BALB/c mice improved the brain uptake in comparison with the aqueous formulation.”
BackgroundMethodDehelean, C. A., Feflea, S., Ganta, S., & Amiji, M. M. (2011) · Journal of Biomedical Nanotechnology · doi:10.1166/jbn.2011.1297 · Cited by 72
Self-citationPreparation of nanoemulsions by phase inversion temperature (PIT)
Jintapattanakit, A. (2018) · doi:10.29090/psa.2018.01.001 · Cited by 68
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Effects of silymarin nanoemulsion against carbon tetrachloride-induced hepatic damage
Parveen, R., Baboota, S., Ali, J., Ahuja, A., Vasudev, S. S., & Ahmad, S. (2011) · Archives of pharmacal research · doi:10.1007/s12272-011-0510-8 · Cited by 64
“The nanoemulsion approach is a versatile technique that has been utilized to increase the solubility of poorly aqueous-soluble drug molecules for better oral bioavailability and therapeutic activity (Tiwari and Amiji, 2006; Khandavilli and Panchagnula, 2007; Vyas et al., 2008; Javed et al., 2010).”
MethodCritical Review of Lipid-Based Nanoparticles as Carriers of Neuroprotective Drugs and Extracts
Fernandes, F., Dias-Teixeira, M., Delerue-Matos, C. M., & Grosso, C. (2021) · Nanomaterials · doi:10.3390/nano11030563 · Cited by 81
“Saquinavir Flaxseed or safflower oil Egg PC: deoxycholic acid 60 ◦C Oil, drug, ethanol 10 min, 21% amplitude Continuous DLS, TEM, in vivo studies [86]”
BackgroundNanotechnology for CNS delivery of bio-therapeutic agents
Shah, L. K., Yadav, S. K., & Amiji, M. M. (2013) · Drug Delivery and Translational Research · doi:10.1007/s13346-013-0133-3 · Cited by 64
“Lastly, hydrophobic payloads and imaging agents can be readily incorporated in the oil phase of the nanoemulsions [24, 25].”
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“demonstrated higher efficacy of PTX and saquinavir from microemulsions containing PUFA rich owing to enhanced oral drug absorption [25,26].”
BackgroundMicroemulsions and Nanoemulsions for Targeted Drug Delivery to the Brain
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“, report significant enhancement in absorption of paclitaxel and saquinavir following oral administration of NE comprising oils rich in PUFA [18, 210].”
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“Our results are in agreement with the observations by Vyas and coworkers, who reported higher brain permeability of saquinavir following its oral administration using nanoemulsion formulation approach (Vyas et al., 2008).”
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Qhattal, H. S. S., Wang, S. F., Salihima, T., Srivastava, S., & Liu, X. (2011) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf202612b · Cited by 50
Dodiya, S., Chavhan, S., Sawant, K., & Korde, A. G. (2011) · Journal of Microencapsulation · doi:10.3109/02652048.2011.590612 · Cited by 48
“For saquinavir, enhanced oral bioavailability and brain disposition using formulation such as nanoemulsion has been reported (Vyas et al., 2008).”
BackgroundAn Excellent Delivery System for Improving the Oral Bioavailability of Natural Vitamin E in Rats
Gong, Y.-H., Wu, Y.-K., Zheng, C., Fan, L.-Y., Xiong, F., & Zhu, J.-B. (2012) · AAPS PharmSciTech · doi:10.1208/s12249-012-9819-y · Cited by 47
Carvalho, V. F. M., Salata, G. C., de Matos, J. K. R., Costa-Fernandez, S., Chorilli, M., Steiner, A., de Araújo, G. D., Silveira, E., Costa-Lotufo, L., & Lopes, L. B. (2019) · International journal of pharmaceutics · doi:10.1016/j.ijpharm.2019.118460 · Cited by 46
Nanotechnology approaches to eradicating HIV reservoirs
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“[228,229], nanogel [230], nanosuspensions [231], and polymeric nanoparticles [232–234].”
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“Edible oil has been used to prepare NE for oral administration; for instance the human immunodeficiency virus protease inhibitor saquinavir has increased its brain bioavailability fivefold with no signs of toxicity [32].”
MethodMohammadi, K., Sani, M. A., Azizi-lalabadi, M., & Mcclements, D. (2022) · Advances in Colloid and Interface Science · doi:10.1016/j.cis.2022.102734 · Cited by 44
Ramires, O., Alves, B. M. D. S., Barros, P., Rodrigues, J. L., Ferreira, S. P., Monteiro, L. K. S., Araújo, G. D. M. S., Fernandes, S. S., Vaz, G., Dora, C. L., et al. (2021) · Neurotoxicity research · doi:10.1007/s12640-021-00362-w · Cited by 44
“In another study, the oral bioavailability and distribution to the brain were significantly enhanced with saquinavir delivered in nanoemulsions (Vyas et al. 2008).”
BackgroundKandadi, P., Afzal, S. M., Kumar, P. U., Ajumeera, R., & Veerabrahma, K. (2011) · Colloids and Surfaces B Biointerfaces · doi:10.1016/j.colsurfb.2011.04.013 · Cited by 44
Ghalamfarsa, G., Hojjat‐Farsangi, M., Mohammadnia‐Afrouzi, M., Anvari, E., Farhadi, S., Yousefi, M., & Jadidi‐Niaragh, F. (2016) · Journal of Immunotoxicology · doi:10.3109/1547691x.2016.1159264 · Cited by 53
“The size of nano-emulsions is <500 nm in diameter; these can successfully incorporate poorly soluble drugs (Ganta et al. 2008; Vyas et al. 2008).”
Background
Metadata
- Authors
- Vyas, T. K., Shahiwala, A., & Amiji, M. M.
- Affiliations
- Northeastern University (US)
- Corresponding author
- Amiji, Mansoor M.
- Venue
- International Journal of Pharmaceutics
- Publisher
- Elsevier BV
- Published
- 2008-01
- Volume
- 347
- Issue
- 1-2
- Pages
- 93-101
- ISSN
- 0378-5173 (ISSN-L)
- PMC
- PMC2213794
- OpenAlex
- W2069726112
- Cited by
- 264
- References
- 25
- Citations by year
- 2026: 1 · 2025: 8 · 2024: 5 · 2023: 8 · 2022: 8 · 2021: 18 · 2020: 18 · 2019: 18 · 2018: 22 · 2017: 19 · 2016: 23 · 2015: 16 · 2014: 16 · 2013: 23 · 2012: 21
- FWCI
- 5.44
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- International Journal of Pharmaceutics (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (R01CA119617)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Drug Solubulity and Delivery Systems
- Life Sciences › Agricultural and Biological Sciences › Food Science › Proteins in Food Systems
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Keywords
- saquinavir, nanoemulsions, oral bioavailability, brain distribution, HIV protease inhibitors, polyunsaturated fatty acids, linseed oil, deoxycholic acid, drug absorption, HIV/AIDS treatment, drug delivery
- MeSH terms
- Sunflower Oil, Administration, Oral, Animals, Biological Availability, Brain, Deoxycholic Acid, Emulsions, Injections, Intravenous, Linseed Oil, Male, Mice, Inbred BALB C, Particle Size, Phosphatidylcholines, Plant Oils, Sonication, Surface Properties, HIV Protease Inhibitors, Saquinavir, Area Under Curve, Nanotechnology, Microscopy, Electron, Transmission, Mice, Static Electricity
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