Polylactic Acid-Based Patterned Matrixes for Site-Specific Delivery of Neuropeptides On-Demand: Functional NGF Effects on Human Neuronal Cells

Abstract

The patterned microchamber arrays based on biocompatible polymers are a versatile cargo delivery system for drug storage and site-/time-specific drug release on demand. However, functional evidence of their action on nerve cells, in particular their potential for enabling patterned neuronal morphogenesis, remains unclear. Recently, we have established that the polylactic acid (PLA)-based microchamber arrays are biocompatible with human cells of neuronal phenotype and provide safe loading for hydrophilic substances of low molecular weight, with successive site-specific cargo release on-demand to trigger local cell responses. Here, we load the nerve growth factor (NGF) inside microchambers and grow N2A cells on the surface of patterned microchamber arrays. We find that the neurite outgrowth in local N2A cells can be preferentially directed towards opened microchambers (upon-specific NGF release). These observations suggest the PLA-microchambers can be an efficient drug delivery system for the sitespecific delivery of neuropeptides on-demand, potentially suitable for the migratory or axonal guidance of human nerve cells.

Patterned Drug-Eluting Coatings for Tracheal Stents Based on PLA, PLGA, and PCL for the Granulation Formation Reduction: In Vivo Studies

“…We have successfully used and described this method earlier in our previous works with epinephrine hydrochloride [ 34 ] and glutamate hydrochloride [ 36 ]. At the same time, the solution poorly wets the polymer surface; therefore, the drop cannot be uniformly distributed over the surface for free drying, as in the case of the nerve growth factor solution [ 37 ].…”

“…The shell of such coatings can be synthesized by the adsorption of hydrophilic oppositely charged polyelectrolytes (layer-by-layer method) [ 31 , 32 , 33 ], as well as from hydrophobic polymers: PLA [ 33 ], PLGA [ 34 ], and PCL [ 35 ]. Microchamber arrays are suitable for loading a wide range of both poorly and well-water-soluble substances with low [ 34 , 36 ] and high [ 37 , 38 ] molecular weight. Such coatings have been demonstrated to be sensitive to ultrasound [ 33 , 34 ] and NIR-laser radiation [ 39 ] after shells were modified with photo adsorbent agents such as gold coating [ 40 , 41 ] or nanoparticles [ 37 ] and carbon dots aggregates [ 38 , 42 ].…”

“…Microchamber arrays are suitable for loading a wide range of both poorly and well-water-soluble substances with low [ 34 , 36 ] and high [ 37 , 38 ] molecular weight. Such coatings have been demonstrated to be sensitive to ultrasound [ 33 , 34 ] and NIR-laser radiation [ 39 ] after shells were modified with photo adsorbent agents such as gold coating [ 40 , 41 ] or nanoparticles [ 37 ] and carbon dots aggregates [ 38 , 42 ]. The site-specific laser-induced release of glutamate hydrochloride stimulated the response from neuronal-type cells (N2A) located near the open chambers [ 36 ], controlled nerve growth factor release stimulated the growth and proliferation [ 37 ].…”

“…Such coatings have been demonstrated to be sensitive to ultrasound [ 33 , 34 ] and NIR-laser radiation [ 39 ] after shells were modified with photo adsorbent agents such as gold coating [ 40 , 41 ] or nanoparticles [ 37 ] and carbon dots aggregates [ 38 , 42 ]. The site-specific laser-induced release of glutamate hydrochloride stimulated the response from neuronal-type cells (N2A) located near the open chambers [ 36 ], controlled nerve growth factor release stimulated the growth and proliferation [ 37 ]. It was shown in vivo that ultrasound-indicated adrenaline release from PLGA-based microchamber arrays led to the immediate vascular reaction [ 34 ].…”

“Smart” Polylactic Acid Films with Ceftriaxone Loaded Microchamber Arrays for Personalized Antibiotic Therapy

“…PLA polymer-made MCAs exhibit sufficient mechanical properties to keep structural parameters avoiding unnecessary deformation, facilitate loading due to smooth surface, and improve cargo retain compared to PCL and PLGA [31]. In vitro and in vivo studies have shown that such PLA-based MCAs are completely biocompatible and biodegradable [29,34,35]. MCAs are suitable for carrying a wide range of substances with different molecular weights, in particular, enzymes [30], polysaccharides [36], fluorescent dyes [37], neurotransmitters [34], hormones [31,32], and growth factors [35].…”