Nanoparticulate devices for brain drug delivery

Abstract

The blood-brain barrier (BBB) limits the transport of therapeutic molecules from the blood compartment into the brain, thus greatly reducing the species of therapeutic compounds that can be efficiently accumulated in the central nervous system (CNS). Various strategies have been proposed for improving the delivery of drugs to this tissue, and numerous invasive and noninvasive methods have been proposed by different scientists in an attempt to circumvent the BBB and to increase the delivery of drug compounds into the brain. An interesting alternative, in the solution of this problem and also that of reaching a suitable target in the CNS, has recently been provided through the use of nanoparticulate colloidal devices as a noninvasive technique for brain drug delivery. These systems offer diverse advantages over invasive strategies, because (1) they are designed using biocompatible and biodegradable materials; (2) they avoid the disruption and/or modification of the BBB; and (3) they modulate the biopharmaceutical properties of the entrapped drugs. Moreover, the possibility of targeting specific brain tissue, thanks to ligands linked to the surface of the nanoparticulate colloidal devices, confers the necessary characteristics for the treatment of CNS pathologies to these drug carriers. The aim of this review is to focus on describing the main strategies in use for designing nanoparticulate colloidal devices for CNS delivery, their potentiality as noninvasive strategies in the delivery of drugs to the cerebral tissues, and their biological and clinical applications in cerebral drug delivery.

Characterization of cellular uptake and toxicity of aminosilane-coated iron oxide nanoparticles with different charges in central nervous system-relevant cell culture models

“…One involves various surface modifications using specific ligands to overcome BBB by receptormediated transcytosis. 21,22 For example, apolipoprotein E-modified human serum albumin nanoparticles cross the BBB via low-density lipoprotein-mediated endocytosis. 23 Another strategy involves magnetic targeting of long circulating magnetic nanoparticles and disruption of the BBB.…”

“…The bEnd.3 cells (passage number [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] were cultured in Dulbecco's Modified Eagle Medium (DMEM) (Hyclone, Logan, UT) supplemented with 10% heat-inactivated fetal bovine serum (FBS; Hyclone), 50 U/ mL penicillin and streptomycin (MP Biomedicals, Solon, OH, USA) at 37°C and 5% CO 2 . Cells were expanded in T-75 tissue culture flasks and seeded at 2 × 10 4 cells per cm 2 on six-or twelve-well plates for uptake and cytotoxicity studies, respectively.…”

Physicochemical features and transfection properties of chitosan/poloxamer 188/poly(D,L-lactide-co-glycolide) nanoplexes

“…8 PLGA nanoparticles have been extensively investigated for their capacity to deliver various agents, including anticancer drugs, 9,10 proteins, and peptides 11 in a sustained and targeted manner. They have also demonstrated efficiency as drug delivery devices that are able to overcome obstacles, such as the blood-brain barrier 12,13 and other barriers in gastrointestinal, 14 nasal, 15 and ocular 16 tissues. Unfortunately, PLGA has a negative charge, which limits its interaction with DNA/RNA, so cationic compounds have been combined with this polymer in order to condense genetic material efficiently.…”

<i>In Situ</i> Hydrogel Formulation for Intra-Articular Application of Diclofenac Sodium-Loaded Polymeric Nanoparticles

“…When the zeta potential value of nanoparticles is between ±30 mV, the colloidal systems show no aggregation and they form stable dispersions that depends on the repulsion forces between particles. 27,28 From this point of view, nanoparticles' stability confirmed via zeta potential analysis. The zeta potential value of F6 coded formulation was found as -29.6±2.7 mV which is in the theoretical ±30 mV stability range and no aggregation was observed after three months storage at 25°C and 60% relative humidity.…”