Nanoemulsion-based intranasal drug delivery system of saquinavir mesylate for brain targeting
Open accessAbstract
The central nervous system (CNS) is an immunological privileged sanctuary site-providing reservoir for HIV-1 virus. Current anti-HIV drugs, although effective in reducing plasma viral levels, cannot eradicate the virus completely from the body. The low permeability of anti-HIV drugs across the blood-brain barrier (BBB) leads to insufficient delivery. Therefore, developing a novel approaches enhancing the CNS delivery of anti-HIV drugs are required for the treatment of neuro-AIDS. The aim of this study was to develop intranasal nanoemulsion (NE) for enhanced bioavailability and CNS targeting of saquinavir mesylate (SQVM). SQVM is a protease inhibitor which is a poorly soluble drug widely used as antiretroviral drug, with oral bioavailability is about 4%. The spontaneous emulsification method was used to prepare drug-loaded o/w nanoemulsion, which was characterized by droplet size, zeta potential, pH, drug content. Moreover, ex-vivo permeation studies were performed using sheep nasal mucosa. The optimized NE showed a significant increase in drug permeation rate compared to the plain drug suspension (PDS). Cilia toxicity study on sheep nasal mucosa showed no significant adverse effect of SQVM-loaded NE. Results of in vivo biodistribution studies show higher drug concentration in brain after intranasal administration of NE than intravenous delivered PDS. The higher percentage of drug targeting efficiency (% DTE) and nose-to-brain drug direct transport percentage (% DTP) for optimized NE indicated effective CNS targeting of SQVM via intranasal route. Gamma scintigraphy imaging of the rat brain conclusively demonstrated transport of drug in the CNS at larger extent after intranasal administration as NE.
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Nanoemulsions can be used to solve problems of drug solubility and/or drug stability, including oxidation, pH, hydrolysis and enzymatic degradation at the mucosal level under physiological conditions.
“NEs can be used to solve problems of drug solubility and/or of drug stability (oxidation, pH, hydrolysis and enzymatic degradation at the mucosal level, under physiological conditions) [24,28].”
From Nanoemulsions for “Nose-to-Brain” Drug Delivery (2019) · cites this paper as [28]
The Introduction says saquinavir has poor water solubility and that nanoemulsions can protect encapsulated drugs from biological or chemical degradation; the Preparation section describes dissolving saquinavir in the formulation. The paper does not specify protection against oxidation, pH changes, hydrolysis, or enzymatic degradation at the mucosal level under physiological conditions. Page numbers are unavailable in our copy. (LLM, conf=0.86)
Experimental — accuracy not yet measuredSaquinavir mesylate is a protease inhibitor with activity against HIV-1; its bioavailability is low due to low water solubility, and its permeability through the blood-brain barrier is poor because it is a P-glycoprotein and cytochrome P450 substrate.
“Saquinavir mesylate is a protease inhibitor with activity against HIV-Type 1 (HIV-1). However, its bioavailability is low, owing to its low solubility in water. Furthermore, saquinavir permeability through the BBB is poor and is a P-glycoprotein and cytochrome P450 substrate.”
From Nanoemulsions for “Nose-to-Brain” Drug Delivery (2019) · cites this paper as [28]
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Experimental — accuracy not yet measuredAfter initial HIV infection, the CNS is a region in which HIV viruses constitute an anatomic reservoir and from which they can reactivate infection; brain infection from HIV can determine neuro-AIDS, a form of dementia and cognitive impairment.
“It is known that after the initial infection, CNS is the region in which HIV viruses constitute a sort of “anatomic reservoir”, and from which they can reactivate the infection. Furthermore, the brain infection from HIV can determine neuro-AIDS, a form of dementia and cognitive impairment.”
From Nanoemulsions for “Nose-to-Brain” Drug Delivery (2019) · cites this paper as [28]
Nanoemulsions showed an increase in drug permeation compared to plain drug suspension, and cilia toxicity was low.
“NEs showed an increase in drug permeation compared to plain drug suspension. Cilia toxicity was low.”
From Nanoemulsions for “Nose-to-Brain” Drug Delivery (2019) · cites this paper as [28]
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- Authors
- Mahajan, H. S., Mahajan, M. S., Nerkar, P. P., & Agrawal, A.
- Affiliations
- Shri Siddhivinayak Ganapati Cancer Hospital (IN)
- Corresponding author
- Mahajan, Hitendra S.
- Venue
- Drug Delivery
- Publisher
- Informa UK Limited
- Published
- 2013-10-16
- Volume
- 21
- Issue
- 2
- Pages
- 148-154
- ISSN
- 1071-7544 (ISSN-L)
- 1521-0464
- OpenAlex
- W2120063106
- Cited by
- 212
- References
- 23
- Citations by year
- 2026: 8 · 2025: 12 · 2024: 17 · 2023: 21 · 2022: 26 · 2021: 28 · 2020: 20 · 2019: 26 · 2018: 15 · 2017: 15 · 2016: 9 · 2015: 12 · 2014: 3
- FWCI
- 4.81
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Drug Delivery (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Inhalation and Respiratory Drug Delivery
- Keywords
- nanoemulsions, intranasal drug delivery, blood-brain barrier, brain targeting, neuroAIDS, HIV-1, antiretroviral drugs, nasal mucosa permeation, tissue distribution, nose-to-brain transport, scintigraphy, poorly water-soluble drugs
- MeSH terms
- Administration, Intranasal, Animals, Blood-Brain Barrier, Brain, Emulsions, Male, Nasal Mucosa, Sheep, Drug Delivery Systems, Rats, Sprague-Dawley, Saquinavir, Rats, Nanoparticles
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