Nose-To-Brain Delivery of PLGA-Diazepam Nanoparticles

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• 作者：Deepak Sharma ; Rakesh Kumar Sharma ; Navneet Sharma ; Reema Gabrani…
• 关键词：controlled release ; nanoparticles ; process optimization ; scintigraphy
• 刊名：AAPS PharmSciTech
• 出版年：2015
• 出版时间：October 2015
• 年：2015
• 卷：16
• 期：5
• 页码：1108-1121
• 全文大小：1,811 KB
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• 作者单位：Deepak Sharma (1)
  Rakesh Kumar Sharma (2)
  Navneet Sharma (2)
  Reema Gabrani (1)
  Sanjeev K. Sharma (1)
  Javed Ali (3)
  Shweta Dang (1)
  
  1. Department of Biotechnology, Jaypee Institute of Information Technology, A-10, Sector 62, Noida, UP, 201307, India
  2. Division of CBRN Defence, Institute of Nuclear Medicine and Allied Sciences, Brig SK Mazumdar Marg, Delhi, 110054, India
  3. Faculty of Pharmacy, Jamia Hamdard, Hamdard Nagar, New Delhi, 110062, India
  
• 刊物主题：Pharmacology/Toxicology; Biotechnology; Biochemistry, general; Pharmacy;
• 出版者：Springer US
• ISSN：1530-9932

文摘

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 148-37 d.nm, polydispersity index 0.04-.45, drug entrapment 69-2%, and zeta potential in the range of ?5 to ?9.24 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 (99mTc) 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-.45, 258, and 61% for 99mTc-DNP (i.n) compared to 99mTc-DS (i.n) (0.38-.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. KEY WORDS controlled release nanoparticles process optimization scintigraphy