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Table 2 Synthetic polymers for BDNF modification or BDNF delivery system

From: Brain-derived neurotrophic factor in Alzheimer’s disease and its pharmaceutical potential

Polymer

Formulation or modification

Preparation

Results

References

PEG

BDNF-PEG2000, BDNF-PEG5000

Coupled PEG to BDNF carboxyls using carbodiimide

PEG conjugation at the C-terminus of BDNF retains the biologic activity and reduces systemic clearance in vivo

[451]

BDNF-PEG mixtures

Covalently attached BDNF to PEG

Mixtures with one and two conjugate products maintain high bioactivity in vitro; improve half-life of BDNF in CSF; enhance the penetration into spinal cord tissue

[452]

BDNF-PEG2000-biotin/SA-OX26 (BDNF chimeric peptide)

(1) Attached a hydrazide to one end of PGE and a biotin moiety to the other end; (2) Prepared OX26/SA by thiol-ether linkage; (3) Coupled PEG to BDNF via hydrazide linkers; (4) Conjugated BDNF-PEG-biotin to OX26/SA

The bioactivity of the BDNF chimeric peptide is identical to native BDNF; transported through BBB after intravenous administration; minimizes rapid clearance of BDNF; increases brain uptake of BDNF to about twofold

[453, 454]

BDNF-PEG2000

BDNF in pH 8.0 borate buffer was reacted with PEG

Enhances the diffusion of BDNF into brain tissues

[427]

BDNF-PEG

N-terminal pegylated form of BDNF

Improves the penetration of BDNF into the spinal cord

[428]

PLGA

BDNF-immobilized PLGA membrane

Incorporated BDNF onto the surfaces of PLGA membrane by heparin immobilization

Controlled release of BDNF for 4 weeks;

protects against cavernous nerve; improves angiogenesis in the corpus cavernosum

[455]

PLA

BDNF/PLA macroporous tubular scaffolds (foams)

(1) Dissolved BDNF in BSA solution and then lyophilized to powder; (2) Dispersed BDNF/BSA powder into PLA/DMC solution

PLA tubular macroporous scaffolds with BDNF enhance cell survival and angiogenesis

[456]

Composite materials

PLGA-PLL-PEG microspheres

(1) Conjugated PLGA-PLL-PEG polymer; (2) Dissolved BDNF/BSA into polymer/DCM solution; (3) Fabricated microspheres by double emulsion technique

Yields greater loading and longer-term delivery of BDNF for more than 60 days; maintains the bioactivity of BDNF

[436]

PLGA microparticles/ PEG hydrogel

(1) Prepared BDNF-loaded PLGA microparticles via water/oil/water emulsion technique; (2) Polymerized PLGA microparticles and PEG hydrogel by UV exposure

Sustained release of BDNF over a period of 56 days; alleviates the reactive glial response; increases the recruitment of astrocytes

[434]

  1. BDNF brain-derived neurotrophic factor, CSF cerebrospinal fluid, BBB brain–blood barrier, HA hyaluronic acid, PEG polyethylene glycol, PLL poly-l-lysine, PLGA poly (lac-co-glycolic acid), SA streptavidin, ADSCs adipose-derived stem cells, PLA poly(d,l-lactic acid), DMC dimethylcarbonate, BSA bovine serum albumin