| Full text | |
| Author(s): |
Garcia, Bianca B. M.
;
Mertins, Omar
;
da Silva, Emerson R.
;
Han, Sang W.
Total Authors: 4
|
| Document type: | Journal article |
| Source: | JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY; v. 92, p. 10-pg., 2024-01-25. |
| Abstract | |
The exploration of lipid-biopolymer hybrid systems has opened new avenues for enhancing nucleic acid delivery in gene therapy. Chitosan-N-arginine (CSA), due to its increased hydrophilicity and intracellular penetration resulting from arginine conjugation, holds promise in such formulations. Despite significant advances in developing novel hybrid systems, the influence of the degree of substitution (DS) in CSA on lipid-CSA hybrid systems (chitosomes) and their complexation with pDNA remains unclear. This study aimed to fill this knowledge gap by examining how the DS in CSA influences chitosome formation and function. We synthesized two CSA variants with different DSs and subsequently produced chitosomes to assess their physicochemical properties and transfection potential. The ligation of arginine to chitosan in CSA preparations was confirmed by FTIR and H1NMR spectroscopy, whereas elemental analysis indicated the DS at 5.7 % (CSA-6) and 3.4 % (CSA-3). Long-term stability was assessed in aqueous dispersions under storage temperatures of 25 degrees C or 4 degrees C, and we observed that CSA-3 and CSA-6 maintained their integrity for 11 and 12 months, respectively. Both chitosomes were successfully complexed with pDNA with the assistance of electrostatic interactions. Thermodynamic parameters indicated an exothermic interaction and a major contribution from the entropy change. Moreover, the chitosomes could protect pDNA from nucleases for 24 h, and the transfection efficiency in HeLa cells reached 21 %. Our findings suggest that while the DS in CSA influences pDNA complexation and compaction, it is not a determinant of the transfection efficiency. These findings will help in the design of improved hybrid nanosystems based on lipids and chitosan derivatives for nucleic acid delivery. (AU) | |
| FAPESP's process: | 20/06913-1 - Development of chitosomes' nanoparticles for modulation of inflammation and angiogenesis by dual delivery: an approach to gene therapy for limb ischemia |
| Grantee: | Bianca Bonetto Moreno Garcia |
| Support Opportunities: | Scholarships in Brazil - Doctorate |
| FAPESP's process: | 21/00971-2 - Crystalline-phase nano cubosome functionalized with biopolymers: development as a drug carrier and in vivo studies in zebrafish (Danio rerio) |
| Grantee: | Omar Mertins |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 15/20206-8 - Modulation of monocytes, macrophages and pericytes by the colony stimulating factor genes to treat murine limb ischemia |
| Grantee: | Sang Won Han |
| Support Opportunities: | Research Projects - Thematic Grants |
| FAPESP's process: | 22/04361-7 - Development of chitosomes for mRNA Delivery to NK cells |
| Grantee: | Bianca Bonetto Moreno Garcia |
| Support Opportunities: | Scholarships abroad - Research Internship - Doctorate |
| FAPESP's process: | 23/03903-3 - Investigation of the role of ANXA1 in limb ischemia recovery and development of gene therapy with non-viral vectors |
| Grantee: | Sang Won Han |
| Support Opportunities: | Regular Research Grants |