Dendrimer grafted albumin nanoparticles for the treatment of post cerebral stroke damages: A proof of concept study.

Abstract

Stroke is the second largest disease of mortality. The biggest hurdle in designing effective brain drug delivery systems is offered by the blood-brain barrier (BBB), which is highly impermeable to many drugs. Albumin nanoparticles (NP) have gained attention due to their multiple ligand binding sites and long circulatory half-life. Citicoline (CIT) is reported to enhance the acetylcholine secretion in the brain and also helps in membrane repair and regeneration. However, the poor BBB permeation of CIT results in lower levels of CIT in the brain. This demands the development of a suitable delivery platform to completely realize the therapeutic benefit of CIT in stroke therapy. This investigation reports the synthesis and characterization of second generation (2.0 G) dendrimer Amplified Albumin (dAA) biopolymer by FTIR, MALDI-TOF, and surface charge (mV). Further, the synthesized biopolymer has been utilized to develop a CIT nanoformulation using a commercially translatable one-pot process. Release of CIT from biopolymer was performed within an acetate buffer at pH 5 and Phosphate buffer at pH 7.4. Further, we investigated the ability of biopolymer to permeate BBB by in vitro permeability assay in bEnd.3 cells. MTT assay of CIT-dAA-NP, CIT-ANP, and 2.0 G PAMAM dendrimers was performed in bEnd.3 cells. Therapeutic efficacy of the synthesized biopolymer was determined by VEGF gene expression within an in vitro hypoxia model in PC12 cells. Thus, this investigation resulted in biopolymers that can be used to deliver any therapeutic agent by altering the permeability of the BBB. Also, cationization by dendrimer grafting is one such strategy that may be used to cationize any other negatively charged polymer, such as albumin. The synthesized biopolymer is not limited to deliver molecules to the brain, but can also be used to increase the loading of negatively-charged drug molecules, siRNA, or any other oligonucleotide.

• Authors: Deepak Pradhan, Vishakha Tambe, Nidhi Raval, Piyush Gondalia, Pallab Bhattacharya, Kiran Kalia, Rakesh K Tekade
• Journal: Colloids and surfaces. B, Biointerfaces (Colloids Surf B Biointerfaces) Vol. 184 Pg. 110488 (Dec 01 2019) ISSN: 1873-4367 [Electronic] Netherlands
• PMID: 31541894 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 Elsevier B.V. All rights reserved.

Chemical References

• Albumins
• Dendrimers
• Drug Carriers
• Nootropic Agents
• PAMAM Starburst
• Cytidine Diphosphate Choline

Topics

• Albumins (chemistry)
• Animals
• Biological Transport (drug effects)
• Blood-Brain Barrier (metabolism)
• Cytidine Diphosphate Choline (administration & dosage, chemistry, pharmacokinetics)
• Dendrimers (chemistry)
• Drug Carriers (administration & dosage, chemistry, pharmacokinetics)
• Drug Delivery Systems (methods)
• Humans
• Mice, Inbred BALB C
• Nanoparticles (chemistry)
• Nootropic Agents (administration & dosage, chemistry, pharmacokinetics)
• PC12 Cells
• Proof of Concept Study
• Rats
• Stroke (drug therapy, metabolism)