Scopus
🔓 Açık Erişim YÖKSİS Eşleşti
Polyphosphate coated nanoparticles: Enzyme-activated charge-reversal gene delivery systems
International Journal of Pharmaceutics · Kasım 2023
YÖKSİS Kayıtları
Polyphosphate coated nanoparticles: Enzyme-activated charge-reversal gene delivery systems
International Journal of Pharmaceutics · 2023 SCI-Expanded
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Makale Bilgileri
DergiInternational Journal of Pharmaceutics
Yayın TarihiKasım 2023
Cilt / Sayfa646
Scopus ID2-s2.0-85173279201
Erişim🔓 Açık Erişim
Özet
Aim: The current study aimed to develop enzyme-activated charge-reversal lipid nanoparticles (LNPs) as novel gene delivery systems. Methods: Palmitic acid was covalently bound to protamine being utilised as transfection promoter to anchor it on the surfaces of LNPs. Green fluorescent protein (GFP) encoding plasmid DNA (pDNA) was ion paired with various cationic counter ions to achieve high encapsulation in LNPs. Protamine-decorated LNPs were prepared by solvent injection method followed by coating with sodium tripolyphosphate (TPP) to generate a bio-inert anionic outer surface. Resulting LNPs were characterised regarding size, polydispersity, zeta potential and encapsulation efficiency. Enzyme-triggered charge-reversal of LNPs was investigated using isolated alkaline phosphatase (ALP) monitoring changes in zeta potential as well as monophosphate release. Furthermore, monophosphate release, cell viability and transfection efficiency were evaluated on a human alveolar epithelial (A549) cell line. Results: Protamine-decorated and TPP-coated (Prot-pDNA/DcChol-TPP) LNPs displayed a mean size of 298.8 ± 17.4 nm and a zeta potential of −13.70 ± 0.61 mV. High pDNA encapsulation was achieved with hydrophobic ion pairs of pDNA with 3ß-[N-(N',N'-dimethylaminoethane)-carbamoyl]cholesterol hydrochloride (DcChol). Zeta potential of Prot-pDNA/DcChol-TPP LNPs reversed to positive values with a total Δ26.8 mV shift upon incubation with ALP. Conformably, a notable amount of monophosphate was released upon incubation of Prot-pDNA/DcChol-TPP LNPs with isolated as well as cell-associated ALP. A549 cells well tolerated LNPs displaying more than 95 % viability. Compared with naked pDNA, unmodified LNPs and control LNPs, Prot-pDNA/DcChol-TPP LNPs showed a significantly increased transfection efficiency. Conclusion: Prot-pDNA/DcChol-TPP LNPs can be regarded as promising gene delivery systems.
Yazarlar (6)
1
Zeynep Burcu Akkuş-Dağdeviren
2
Sema Arisoy
ORCID: 0000-0003-2798-1884
3
Julian David Friedl
4
Andrea Fürst
5
Ahmad Saleh
6
Andreas Bernkop-Schnürch
ORCID: 0000-0003-4187-8277
Anahtar Kelimeler
Charge-reversal
Gene delivery
Lipid nanoparticles
Polyphosphate coating
Protamine
Transfection
Kurumlar
Selçuk Üniversitesi
Selçuklu Turkey
Universitas Mandala Waluya
Kendari Indonesia
Universität Innsbruck
Innsbruck Austria
Metrikler
2
Atıf
6
Yazar
6
Anahtar Kelime