Oftalmol Zh.2014;2:17-21
https://doi.org/10.31288/oftalmolzh201421721
The sustained delivery system of the antiinfection peptide LL37 system — a potentially new treatment method of ocular infections. Report 1. Testing of different nano- and microparticles as carriers of LL37
Buznyk0.
State Institution The Filatov Institute of Eye Diseases and Tissue Therapy of the NAMS of Ukraine, Odessa, (Ukraine)
Purpose. To develop anti-infective peptide (AIP) LL37sustained delivery system that can be used for ocular infections treatment.
Methods. AIPLL37(cathelicidin) was encapsulated in different particles (alginate, chitosan, silica) under magnetic stirring. Encapsulation efficacy (EE) and LL37 release from particles was checked using the ELISA method. The particle morphology was studied by transmission electron or light microscopy. Cytotoxicity of particles with encapsulated LL37was assessed using WST-1 based colorimetric assay.
Results. EE of LL37in the alginate microparticles (AMPs) was 13.8 %. AMP size was 15—20 um. EE of LL37in silica nanoparticles (SiNPs) was 54.4 %. SNPsize was 10—20 nm. Sustained release of LL37in AMPs occurred up to the 7th day and in SNP's — up to the 21st day. No LL37 release occurred from chitosan particles. WST-1 based colorimetric assay showed no increased cytotoxicity regarding human corneal epithelial cells of particles with encapsulated LL37compared to control clear particles.
Conclusion. For the first time micro - and nanoparticle based AIP LL37 sustaineddelivery system was developed. Sustained release of LL37 from AMPs and SiNPs was proved. No cell toxicity was found. SiNP encapsulated LL37showed better EE and longer release of AIP compared to AMP encapsulated LL37.
Key words. Ocular infection, LL37, antiinfection peptide sustained delivery system
References
1.Bareiss B, Ghorbani M, Li F, et al. Controlled release of acyclovir through bioengineered corneal implants with silica nanoparticle carriers. Open Tissue Eng. Regen. Med. J. 2010;3:10-7.
Crossref
2.Barlow PG, Svoboda P, Mackellar A, et al. Antiviral activity and increased host defense against influenza infection elicited by the human cathelicidin LL-37. PLoS ONE. 2011;6(10):e25333.
Crossref
3.Bertino JS Jr. Impact of antibiotic resistance in the management of ocular infections: the role of current and future antibiotics. Clin. Ophthalmol. 2009;3:507-21.
Crossref
4.Brogden K. A. Antimicrobial peptides: pore formers or metabolic inhibitors in bacteria? Nature Rev. Microbiol. 2005;3:238-50.
Crossref
5.Chetoni P, Rossi S, Burgalassi S et al. Comparison of li-posome-encapsulated acyclovir with acyclovir ointment: ocular pharmacokinetics in rabbits. J. Ocul. Pharmacol. Ther. 2004;20(2):169-77.
Crossref
6.Donadio S, Maffioli S, Monciardini P, Sosio M, Jabes D. Antibiotic discovery in the twenty-first century: Current trends and future perspectives. J. Antibiot. (Tokyo). 2010; 63(8):423-30.
Crossref
7.Fresta M, Fontana G, Bucolo C et al. Ocular tolerability and in vivo bioavailability of poly (ethyleneglycol) (PEG)-coated polyethyl-2-cyanoacrylate nanosphere-encapsulat-ed acyclovir. J. Pharm. Sci. 2001;90(3):288- 97.
Crossref
8.Gordon YJ, Huang LC, Romanowski EG et al. Human cathelicidin (LL-37), a multifunctional peptide, is expressed by ocular surface epithelia and has potent antibacterial and antiviral activity. Curr. Eye Res. 2005; 30(5):385- 94.
9.Izquierdo-Barba I, Vallet-RegH M, Kupferschmidt N, et al. Incorporation of antimicrobial compounds in mesoporous silica film monolith. Biomaterials. 2009; 30(29):5729-36.
10.Newman H, Gooding C. Viral ocular manifestations: a broad overview. Rev. Med. Virol. 2013;23(5):281- 94.
11.Ramos R, Domingues L, Gama M. LL37, a human antimicrobial peptide with immunomodulatory properties. Science against microbial pathogens: communicating current research and technological advances: Microbiology Book Series [edit. A. Mnndez-Vilas]. Badajoz : Formatex Research Center. 2011;2:915-25.
12.Steinstraesser L, Tippler B, Mertens J et al. Inhibition of early steps in the lentiviral replication cycle by cathelicidin host defense peptides. Retrovirology. 2005;2:2.