Heparin-based, injectable microcarriers for controlled delivery of interleukin-13 to the brain

Abstract

The anti-inflammatory cytokine IL-13 can be loaded and released from heparin-based cryogel biomaterials for sustained delivery to the brain.

Injectable Cryogels in Biomedicine

“…Macro-scale protein drug delivery systems are used to control the delivery of drugs to specific tissues. Careful material selection is often required for establishing an effective polymer drug delivery system for a particular protein, achieving the desired protein release profile, and maintaining bioactivity [ 56 ]. In drug-loaded cryogels, because the porous structure triggers the burst release of the drug, the use of a nanocarrier to overcome this situation could be a potential candidate for both controlling the drug release rate and enhancing the cryogels [ 57 ].…”

“…Here, microscale cryogels (microcarriers) containing heparin and PEG were employed, and characterization processes were carried out. Immunomodulatory activity of IL-13 loaded microcarriers was evaluated in vitro on bone marrow-derived macrophages and in vivo in mouse brain, and it was emphasized that a slow and sustained IL-13 release was achieved with microcryogels for at least seven days [ 56 ].…”

Glycosaminoglycan-Based Cryogels as Scaffolds for Cell Cultivation and Tissue Regeneration

“…An overview of different cryogels prepared on the basis of HA, CS, and HE and their derivatives, respectively, is provided in Tables 1 and 2. Carrier for pancreative islets [41] Cancer immunotherapy [42] Cytokine release to the brain [43] stem cell culture; RGD-modification-mediated cell adhesion Neural cell cultivation [44,45]…”

“…Due to the known disadvantages of physical crosslinking, such as poor mechanical stability, difficult adjustability of the pore size, and the often-rapid degradation behavior, many researchers use chemical methods of crosslinking [ 53 , 54 ]. Several common low-molecular crosslinking agents such as diepoxides [ 15 ], glutar dialdehyde [ 23 , 37 , 49 ], divinylsulfone [ 17 ], or water-soluble carbodiimides (e.g., 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide) [ 18 , 19 , 20 , 35 , 36 ], mostly in the presence of N-Hydroxysulfosuccinimide (Sulfo-NHS) [ 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 ], have also been used for the preparation of GAG-based cryogels. Besides those low-molecular-weight crosslinkers, also oligomeric bifunctional crosslinkers, for example a polycaprolactone-based diisocyanate (PCl-di-NCO) and poly(ethylene glycol)bis-maleimide (PEG-bis(maleimide)), have been used to initiate crosslinking by urethane formation [ 23 ] and a Diels−Alder click-crosslinked reaction with a furan-modified HA [ 33 , 34 ], respectively.…”

Growth Factor Therapy for Parkinson’s Disease: Alternative Delivery Systems

“…Although numerous studies have shown that intracerebral injection of microencapsulated growth factors including GDNF [33][34][35][36][37][38][39] and vascular endothelial growth factor (VEGF) [34,35,40] can improve parkinsonism in both rodent [34][35][36][37][38][39][40][41][42] and primate [33] models of PD, the main limitation of this approach is that the growth factor release in the brain is rapid and not sustained, a major issue if biomaterial-aided growth factor therapy is to provide meaningful benefit in the decades-long pathogenesis of PD in patients. One potential solution to this could be the use of highly charged microscale depot systems that provide strong electrostatic attraction between the therapeutic protein(s) and the microcarrier [43]. Not only does this result in slower release of the therapeutic protein, but it also has the potential to be refillable or reloadable, although this too is limited as each refill would require intracerebral injection of the growth factor.…”