Neuropeptide in microcapsules
Biodegradable microcapsules will deliver nerve growth factor for neuronal regeneration
Skoltech researchers and their colleagues conducted an in vitro experiment in which they demonstrated the ability to stimulate the growth of neurons in the hippocampus using biodegradable microcapsules to deliver to neurons the neuropeptide necessary for this, nerve growth factor (NGF). An article describing the results of the study was published in the journal Pharmaceuticals (Kopach et al., Biodegradable Microcapsules Loaded with Nerve Growth Factor Enable Neurite Guidance and Synapse Formation).
In medicine, there are many neurodegenerative conditions that can lead to the development of serious diseases and associated with a decrease in the levels of so-called growth factors in the brain. Growth factors – neuropeptides – contribute to the growth, development and survival of neurons. In some clinical studies of Alzheimer's and Parkinson's diseases, it has been shown that a therapeutic effect can be achieved by delivering these growth factors to specific degenerating neurons, but it turned out to be quite difficult to solve this problem in practice. Getting into the systemic circulation like conventional medications, they may not overcome the blood-brain barrier and cause serious side effects. If viruses for gene therapy are used to deliver neuropeptides, then it is not so easy to stop the treatment that has begun, which also raises concerns about its safety.
Researchers from Skoltech and Queen Mary University of London Olga Sindeeva and Gleb Sukhorukov and their colleagues proposed a method of targeted delivery of one of the neuropeptides, nerve growth factor, in a microcapsule with an average size of 2 to 3 microns exactly to the "destination". Poly-L-arginine and dextran were used as materials for the capsule, and layered technology was used for its manufacture: the thinnest films were applied layer by layer, gradually forming a capsule. In previous studies, it was shown that such capsules have biocompatibility: when used on human tissue slices and on rodents, no noticeable side effects were detected.
"The main advantage of Layer-by-Layer (LbL) encapsulation technology is its versatility, and, consequently, the ability to adapt the capsule shell to various functions and different types of cargo. In addition, unlike many other encapsulation methods, LbL encapsulation can be carried out in an aqueous medium, which is especially important for such fragile molecules as peptides, proteins and growth factors," notes Gleb Sukhorukov.
Scientists conducted an experiment on cultures of rat hippocampal neurons and analyzed the result of delivery of microcapsules with neuropeptides to neurons: it turned out that the growth of neurons noticeably increased, and new neutrons began to appear precisely near microcapsules with NGF. It was also found that NGF promotes more active branching of neurites: the result of this process is the formation of the main functional elements of the neuron – axons and dendrites. Finally, it has been shown that neurons treated with NGF microcapsules have the ability to form functional synapses. If the proposed method works in clinical conditions, then the process of neurodegeneration, characteristic of many diseases, can become reversible.
"The properties of LbL microcapsules can be customized for specific applications. Microcapsule features such as biocompatibility, biodegradability and controllability of NGF delivery are determined by the type of polymer from which the capsule shell is created. It is also possible to ensure controlled delivery by acting on the capsule using, for example, ultrasound, laser radiation or a magnetic field," explains Gleb Sukhorukov.
The researchers plan to test the proposed NGF controlled delivery technology for its use for accelerated recovery after injuries that cause damage to nervous tissue. As has been shown in previous studies, a similar approach can be applied to other growth factors, in particular, the main fibroblast growth factor – a protein involved in many biological processes, including embryonic development and tissue repair.
The study was conducted with the participation of specialists from University College London and Saratov State University.
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