Sustained local delivery of bioactive nerve growth factor in the central nervous system via tunable diblock copolypeptide hydrogel depots

Synthesis and Self-Assembly of Well-Defined Block Copolypeptides via Controlled NCA Polymerization

“…In comparison with NGF injected in buffer, depots of NGF dissolved in either K 180 L 20 or E 180 L 20 provided significantly longer delivery of NGF bioactivity, maintaining hypertrophy of local forebrain cholinergic neurons for at least 4 weeks and inducing hypertrophy a further distance away (up to 5 mm) from injection sites [115]. These findings show that depots of block copolypeptide hydrogels injected into CNS can provide sustained delivery within the blood brain barrier of a bioactive protein growth factor that exerts a predicted, quantifiable effect on local cells over a prolonged subacute time.…”

“…Insert Figure 8 In a follow up study, Sofroniew and Deming examined the loading and release of bioactive hydrophilic molecules from K 180 L 20 and E 180 L 20 hydrogels in vitro and in vivo [115]. In vitro tests demonstrated sustained release from dialysis cassettes of the representative protein, lysozyme, dissolved in K 180 L 20 or E 180 L 20 hydrogels.…”

Dynamic and Responsive Growth Factor Delivery from Electrospun and Hydrogel Tissue Engineering Materials

“…This study demonstrated prolonged hypertrophy and a larger region of effect compared to NGF injected in a buffer solution. [54] Although the loading is simple, the release profile of drugs and growth factors from hydrogels is dependent on interactions between the two materials. From MAX8 peptide hydrogels, for example, positively charged proteins diffuse out while negatively charged proteins adsorb to the hydrogel showing little diffusion.…”

Triggered Copolypeptide Hydrogel Degradation Using Photolabile Lysine Protecting Groups

“…20 We have previously shown that these physical hydrogels are injectable for minimally invasive application, can entrap and passively release both protein and small molecule cargos, and can form deposits and are well tolerated in central nervous system tissues in vivo in mice. [21][22][23][24] To create photodegradable DCH, we envisioned replacement of hydrophobic leucine residues with lysine residues containing photolabile protecting groups, where the protected residues would be hydrophobic to promote gelation, and once deprotected the lysine residues would become hydrophilic resulting in dissolution (Scheme 1).…”

“…Since the dyes were anionic, they were expected to complex the cationic poly(L-lysine) segments of the gels and only slowly diffuse from the gels. 22 Red and blue dyed gels were placed in contact, and then allowed to stand for 48 hours, either with or without irradiation (Figure 3). In the control sample with no irradiation, only minimal dye diffusion across the red/blue interface was observed, which showed good dye entrapment within the hydrogels.…”