scholarly journals Cationic bovine serum albumin (CBA) conjugated poly lactic-co-glycolic acid (PLGA) nanoparticles for extended delivery of methotrexate into brain tumors

RSC Advances ◽  
2016 ◽  
Vol 6 (92) ◽  
pp. 89040-89050 ◽  
Author(s):  
Prashant Kesharwani ◽  
Ashay Jain ◽  
Atul Jain ◽  
Amit K. Jain ◽  
Neeraj Kumar Garg ◽  
...  

Current strategies for the treatment of brain tumors have been hindered primarily by the presence of the highly lipophilic, insurmountable blood–brain barrier (BBB).

1991 ◽  
Vol 261 (2) ◽  
pp. R478-R483
Author(s):  
M. Shimon-Hophy ◽  
K. C. Wadhwani ◽  
K. Chandrasekaran ◽  
D. Larson ◽  
Q. R. Smith ◽  
...  

Regional blood-brain barrier permeability-surface area products (PAs) of cationized bovine serum albumin (cBSA) with isoelectric point (pI) approximately 8 or greater than or equal to 11 and of native bovine serum albumin (nBSA;pI approximately 4) were determined in awake male Sprague-Dawley rats after bolus intravenous injection. The albumins were labeled with 125I. Brain uptakes were assessed by autoradiography and by direct assay of radioactivity in brain regions. nBSA uptake into brain was statistically insignificant over 3 h, whereas cBSA uptake was significantly even at 6 min. Mean PA values of cBSA with pI approximately 11 (1.69-2.65 x 10(-5) ml.s-1.g-1) in most brain regions were twofold higher than PAs of cBSA with pI approximately 8 (0.98-1.37 x 10(-5) ml.s-1.g-1), whereas mean PA for nBSA did not differ significantly from zero. Autoradiographs of brain slices and net distributions in brain compartments at 6 and 30 min after injection suggested that cBSA entered the brain parenchyma via blood vessels and cerebrospinal fluid but that the former was the main route. The results quantitate for the first time regional brain PA values for cationized proteins and suggest specific mechanisms at cerebral blood vessels that distinguish transport of cationized from noncationized macromolecules.


Pharmaceutics ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 72 ◽  
Author(s):  
Gina P. Hoyos-Ceballos ◽  
Barbara Ruozi ◽  
Ilaria Ottonelli ◽  
Federica Da Ros ◽  
Maria Angela Vandelli ◽  
...  

The treatment of diseases that affect the central nervous system (CNS) represents a great research challenge due to the restriction imposed by the blood–brain barrier (BBB) to allow the passage of drugs into the brain. However, the use of modified nanomedicines engineered with different ligands that can be recognized by receptors expressed in the BBB offers a favorable alternative for this purpose. In this work, a BBB-penetrating peptide, angiopep-2 (Ang–2), was conjugated to poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles through pre- and post-formulation strategies. Then, their ability to cross the BBB was qualitatively assessed on an animal model. Proof-of-concept studies with fluorescent and confocal microscopy studies highlighted that the brain-targeted PLGA nanoparticles were able to cross the BBB and accumulated in neuronal cells, thus showing a promising brain drug delivery system.


2020 ◽  
Vol 29 (11) ◽  
pp. 1956-1975
Author(s):  
Alberto Martínez ◽  
Mai Zahran ◽  
Miguel Gomez ◽  
Johnny Guevara ◽  
Rosemary Pichardo-Bueno ◽  
...  

2010 ◽  
Vol 18 (10) ◽  
pp. 842-848 ◽  
Author(s):  
Anja Zensi ◽  
David Begley ◽  
Charles Pontikis ◽  
Celine Legros ◽  
Larisa Mihoreanu ◽  
...  

1996 ◽  
Vol 84 (3) ◽  
pp. 494-502 ◽  
Author(s):  
Bernhard Zünkeler ◽  
Richard E. Carson ◽  
Jeffrey Olson ◽  
Ronald G. Blasberg ◽  
Mary Girton ◽  
...  

✓ Hyperosmolar blood-brain barrier (BBB) disruption remains controversial as an adjuvant therapy to increase delivery of water-soluble compounds to extracellular space in the brain in patients with malignant brain tumors. To understand the physiological effects of BBB disruption more clearly, the authors used positron emission tomography (PET) to study the time course of BBB permeability in response to the potassium analog rubidium-82 (82Rb, halflife 75 seconds) following BBB disruption in anesthetized adult baboons. Mannitol (25%) was injected into the carotid artery and PET scans were performed before and serially at 8- to 15-minute intervals after BBB disruption. The mean influx constant (K1), a measure of permeability-surface area product, in ipsilateral, mannitol-perfused mixed gray- and white-matter brain regions was 4.9 ± 2.4 µl/min/ml (± standard deviation) at baseline and increased more than 100% (ΔK1 = 9.4 ± 5.1 µl/min/ml, 18 baboons) in brain perfused by mannitol. The effect of BBB disruption on K1 correlated directly with the total amount of mannitol administered (p < 0.005). Vascular permeability returned to baseline with a halftime of 24.0 ± 14.3 minutes. The mean brain plasma volume rose by 0.57 ± 0.34 ml/100 ml in ipsilateral perfused brain following BBB disruption. This work provides a basis for the in vivo study of permeability changes induced by BBB disruption in human brain and brain tumors.


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