Nose-To-Brain Delivery of PLGA-Diazepam Nanoparticles
Open accessAbstract
The objective of the present investigation was to optimize diazepam (Dzp)-loaded poly(lactic-co-glycolic acid) nanoparticles (NP) to achieve delivery in the brain through intranasal administration. Dzp nanoparticles (DNP) were formulated by nanoprecipitation and optimized using Box-Behnken design. The influence of various independent process variables (polymer, surfactant, aqueous to organic (w/o) phase ratio, and drug) on resulting properties of DNP (z-average and drug entrapment) was investigated. Developed DNP showed z-average 148-337 d.nm, polydispersity index 0.04-0.45, drug entrapment 69-92%, and zeta potential in the range of -15 to -29.24 mV. Optimized DNP were further analyzed by differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), ex-vivo drug release, and in-vitro cytotoxicity. Ex-vivo drug release study via sheep nasal mucosa from DNP showed a controlled release of 64.4% for 24 h. 3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay performed on Vero cell line showed less toxicity for DNP as compared to Dzp suspension (DS). Gamma scintigraphy and biodistribution study of DNP and DS was performed on Sprague-Dawley rats using technetium-99m-labeled ((99m)Tc) Dzp formulations to investigate the nose-to-brain drug delivery pathway. Brain/blood uptake ratios, drug targeting efficiency, and direct nose-to-brain transport were found to be 1.23-1.45, 258, and 61% for (99m)Tc-DNP (i.n) compared to (99m)Tc-DS (i.n) (0.38-1.06, 125, and 1%). Scintigraphy images showed uptake of Dzp from nose-to-brain, and this observation was in agreement with the biodistribution results. These results suggest that the developed poly(D,L-lactide-co-glycolide) (PLGA) NP could serve as a potential carrier of Dzp for nose-to-brain delivery in outpatient management of status epilepticus.
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Nose-to-brain drug delivery is a painless, non-invasive administration route that can deliver therapeutic agents into the brain by bypassing the blood-brain barrier.
“Nose-to-brain drug delivery is a painless, non-invasive administration route that can be used to deliver therapeutic agents into the brain by bypassing the BBB [10,14,15,16,17].”
From Nanoemulsions for “Nose-to-Brain” Drug Delivery (2019) · cites this paper as [15]
The Introduction describes nasal delivery as noninvasive and says drugs can reach the brain while bypassing the BBB. The Discussion contrasts it with intravenous administration, which can cause local pain, but our copy does not establish that nasal administration itself is painless. (LLM, conf=0.85)
Experimental — accuracy not yet measuredNasal administration of drugs using the nose-to-brain pathway allows direct drug targeting into the brain, avoiding the first-pass effect and bypassing the BBB.
“The nasal administration of drugs using the nose-to-brain pathway allows direct drug targeting into the brain, avoiding the first-pass effect and bypassing the BBB.”
From Nanoemulsions for “Nose-to-Brain” Drug Delivery (2019) · cites this paper as [15]
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References 53 · Cited by 127
Research works printed but not linked: 4
- Fessi et al. Process for the preparation of dispersible colloidal systems of a substance in the form of nanoparticles. US Patent 1992; 5,118,528.
- Sharma D, Gabrani R, Sharma SK, Ali J, Dang S. Development of midazolam loaded PLGA nanoparticles for treatment of status epilepticus. Adv Sci Lett. 2014;20:1526-30.
- Prajapati RK, Mahajan HS, Surana SJ. PLGA based mucoadhesive microspheres for nasal delivery: in vitro/ex vivo studies. Indian J Novel Drug Deliv. 2011;3:9-16.
- Sylaja B, Srinivasan S. Experimental and theoretical investigation of spectroscopic properties of diazepam. Int J Chem Tech Res. 2012;4:361-76.
- Authors
- Sharma, D., Sharma, R. K., Sharma, N., Gabrani, R., Sharma, S. K., Ali, J., & Dang, S.
- Affiliations
- Jaypee Institute of Information Technology (IN)
- Institute of Nuclear Medicine & Allied Sciences (IN)
- Jamia Hamdard (IN)
- Corresponding author
- Dang, Shweta
- Venue
- AAPS PharmSciTech
- Published
- 2015-02-21
- Volume
- 16
- Issue
- 5
- Pages
- 1108-1121
- ISSN
- 1530-9932 (ISSN-L)
- PMC
- PMC4674633
- OpenAlex
- W2035838068
- Cited by
- 127
- References
- 53
- Citations by year
- 2026: 4 · 2025: 12 · 2024: 14 · 2023: 15 · 2022: 12 · 2021: 16 · 2020: 21 · 2019: 8 · 2018: 12 · 2017: 5 · 2016: 5 · 2015: 3
- FWCI
- 4.61
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- AAPS PharmSciTech (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Department of Biotechnology, Ministry of Science and Technology, India
- National Institute of Immunology
- Jaypee Institute of Information Technology
- 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
- diazepam, PLGA nanoparticles, nose-to-brain delivery, intranasal drug delivery, nanoprecipitation, Box-Behnken design, technetium-99m radiolabeling, tissue distribution, encapsulation efficiency, nanoparticle cytotoxicity, status epilepticus
- MeSH terms
- Polylactic Acid-Polyglycolic Acid Copolymer, Administration, Intranasal, Animals, Brain, Calorimetry, Differential Scanning, Cell Survival, Chlorocebus aethiops, Diazepam, Drug Carriers, Drug Compounding, Male, Nasal Mucosa, Particle Size, Polyglycolic Acid, Chemical Precipitation, Solubility, Surface-Active Agents, Tissue Distribution, Vero Cells, Rats, Sprague-Dawley, Spectroscopy, Fourier Transform Infrared, Radiopharmaceuticals, Lactic Acid, Nanotechnology, Nanoparticles, Nasal Absorption
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