Epidermal lipoxygenase enzyme extracted from Ambystoma mexicanum (AmbLOXe) is known to accelerate the wound-healing process. AmbLOXe as a protein suffers from inactivation and losing its activity during formulation. Therefore, a delivery system that protects AmbLOXe from inactivation and preserves its activity is needed. We prepared AmbLOXe-loaded pectin nanoparticles (AmbLOXe Pec-NPs) and placed them into an alginate hydrogel. AmbLOXe Pec-NPs incorporation into the alginate hydrogel provides a means for controlled and sustained delivery of AmbLOXe to the wound site. Furthermore, the suitable swelling behavior and mechanical properties of AmbLOXe Pec-NPs alginate hydrogel make it feasible for clinical use. AmbLOXe Pec-NPs alginate hydrogel significantly enhanced the wound-healing process on the rat full-thickness excisional wounds, increased the rate of wound closure, enhanced the re-epithelialization and decreased the incidence of abnormal scarring. AmbLOXe Pec-NPs alginate hydrogel can be proposed as an effective wound hydrogel for improving wound healing with minimal scarring.
DreifkeMBJayasuriyaAAJayasuriyaAC.Current wound healing procedures and potential care. Mater Sci Eng C Mater Biol Appl2015;
48: 651–662.
2.
VowdenPVowdenK.The economic impact of hard-to-heal wounds: promoting practice change to address passivity in wound management. Int Wound J2016;
7: 10–15.
3.
VelnarTBaileyTSmrkoljV.The wound healing process: an overview of the cellular and molecular mechanisms. J Int Med Res2009;
37: 1528–1542.
4.
ReesiFMinaiyanMTaheriA.A novel lignin-based nanofibrous dressing containing arginine for wound-healing applications. Drug Deliv Transl Res2018;
8: 111–122.
5.
Hoseinpour NajarMMinaiyanMTaheriA.Preparation and in vivo evaluation of a novel gel-based wound dressing using arginine–alginate surface-modified chitosan nanofibers. J Biomater Appl2018;
32: 689–701.
6.
KhanbanhaNAtyabiFTaheriA, et al.
Healing efficacy of an EGF impregnated triple gel based wound dressing: in vitro and in vivo studies. Biomed Res Int2014;
2014: 1–10.
7.
BoatengJSMatthewsKHStevensHN, et al.
Wound healing dressings and drug delivery systems: a review. J Pharm Sci2008;
97: 2892–2923.
8.
ChiuCTLeeJSChuCS, et al.
Development of two alginate-based wound dressings. J Mater Sci Mater Med2008;
19: 2503–2013.
9.
PaulWSharmaCP.Chitosan and alginate wound dressings: a short review. Trends Biomater Artif Organs2004;
18: 18–23.
10.
SmithHM. Developmental biology of the axolotl. In: ArmstrongJBMalacinskiGM (eds) Discovery of the axolotl and its early history in biological research.
New York:
Oxford University Press, 1989, pp. 3–12.
11.
MengerBVogtPMAllmelingC, et al.
AmbLOXe – an epidermal lipoxygenase of the Mexican axolotl in the context of amphibian regeneration and its impact on human wound closure in vitro. Ann Surg2011;
253: 410–418.
12.
StammAStraußSVogtP, et al.
Positive in vitro wound healing effects of functional inclusion bodies of a lipoxygenase from the Mexican axolotl. Microb Cell Fact2018;
17: 57.
13.
VogtPMengerBReimers-FadhlaouiK. Lipoxygenase and its use in wound healing. Medizinische Hochschule Hannover, US 9,066,937, 2015.
14.
MengerBVogtPMKuhbierJW, et al.
Applying amphibian limb regeneration to human wound healing: a review. Ann Plast Surg2010;
65: 504–510.
15.
LosiPBrigantiEErricoC, et al.
Fibrin-based scaffold incorporating VEGF-and bFGF-loaded nanoparticles stimulates wound healing in diabetic mice. Acta Biomater2013;
9: 7814–7821.
16.
KatasHWenCYSiddiqueMI, et al.
Thermoresponsive curcumin/DsiRNA nanoparticle gels for the treatment of diabetic wounds: synthesis and drug release. Ther Deliv2017;
8: 137–150.
17.
Dos SantosMAGrenhaA.Polysaccharide nanoparticles for protein and peptide delivery: exploring less-known materials. In: RossenD (ed) Advances in protein chemistry and structural biology.
Vol. 98.
Cambridge, UK:
Academic Press, 2015, pp.223–261.
18.
SaghazadehSRinoldiCSchotM, et al.
Drug delivery systems and materials for wound healing applications. Adv Drug Deliv Rev2018;
127: 138–166.
19.
TahanMMovahedian-AttarAAbbasianM, et al.
Cloning and expression of epidermal lipoxygenase from Ambystoma mexicanum (LOXe) in Escherichia coli. J Isfahan Med Sch2014;
31: 2162–2170.
20.
SharmaRAhujaMKaurH.Thiolated pectin nanoparticles: preparation, characterization and ex vivo corneal permeation study. Carbohydr Polym2012;
87: 1606–1610.
21.
KrugerNJ.The Bradford method for protein quantitation. In: WalkerJM (ed.) The protein protocols handbook.
New Jersey:
Humana Press, 2002, pp.15–21.
22.
MohandasAAnishaBSChennazhiKP, et al.
Chitosan–hyaluronic acid/VEGF loaded fibrin nanoparticles composite sponges for enhancing angiogenesis in wounds. Colloids Surf B Biointerf2015;
127: 105–113.
23.
KochRBSternBFerrariCG.Linoleic acid and trilinolein as substrates for soybean lipoxidase (s). Arch Biochem Biophys1958;
78: 165–179.
24.
SingerAJChoiYRashelM, et al.
The effects of topical nitric oxide on healing of partial thickness porcine burns. Burns2018;
44: 423–428.
25.
LiYPPeiYYZhangXY, et al.
PEGylated PLGA nanoparticles as protein carriers: synthesis, preparation and biodistribution in rats. J Control Release2001;
71: 203–211.
26.
PatelAPatelMYangX, et al.
Recent advances in protein and peptide drug delivery: a special emphasis on polymeric nanoparticles. Protein Pept Lett2014;
21: 1102–1120.
27.
MundargiRCBabuVRRangaswamyV, et al.
Nano/micro technologies for delivering macromolecular therapeutics using poly (D, L-lactide-co-glycolide) and its derivatives. J Control Release2008;
125: 193–209.
28.
AshtikarMWackerMG.Nanopharmaceuticals for wound healing – lost in translation?Adv Drug Deliv Rev2018;
129: 194–218.
29.
KheiriAJorfSMMalihipourA, et al.
Synthesis and characterization of chitosan nanoparticles and their effect on Fusarium head blight and oxidative activity in wheat. Int J Biol Macromol2017;
102: 526–538.
30.
SullivanDJCruz-RomeroMCollinsT, et al.
Synthesis of monodisperse chitosan nanoparticles. Food Hydrocoll2018;
83: 355–364.
31.
MitriKShegokarRGohlaS, et al.
Lipid nanocarriers for dermal delivery of lutein: preparation, characterization, stability and performance. Int J Pharm2011;
414: 267–275.
32.
JiFLiJQinZ, et al.
Engineering pectin-based hollow nanocapsules for delivery of anticancer drug. Carbohydr Polym2017;
177: 86–96.
33.
GhasemiSJafariSMAssadpourE, et al.
Production of pectin-whey protein nano-complexes as carriers of orange peel oil. Carbohydr Polym2017;
177: 369–377.
34.
TaheriAAtyabiFNouriFS, et al.
Nanoparticles of conjugated methotrexate-human serum albumin: preparation and cytotoxicity evaluations. J Nanomater2011;
2011: 5.
35.
DingRLXieFHuY, et al.
Preparation of endostatin-loaded chitosan nanoparticles and evaluation of the antitumor effect of such nanoparticles on the Lewis lung cancer model. Drug Deliv2017;
24: 300–308.
36.
HenninkWEvan NostrumCF.Novel crosslinking methods to design hydrogels. Adv Drug Deliv Rev2012;
64: 223–236.
37.
MunarinFTanziMCPetriniP.Advances in biomedical applications of pectin gels. Int J Biol Macromol2012;
51: 681–689.
38.
NešićAOnjiaADavidovićS, et al.
Design of pectin-sodium alginate based films for potential healthcare application: study of chemico-physical interactions between the components of films and assessment of their antimicrobial activity. Carbohydr Polym2017;
157: 981–990.
39.
RezvanianMAminMCNgSF.Development and physicochemical characterization of alginate composite film loaded with simvastatin as a potential wound dressing. Carbohydr Polym2016;
137: 295–304.
40.
LeeSMParkIKKimYS, et al.
Physical, morphological, and wound healing properties of a polyurethane foam-film dressing. Biomater Res2016;
20: 15.
41.
UmorenSAObotIBMadhankumarA, et al.
Performance evaluation of pectin as ecofriendly corrosion inhibitor for X60 pipeline steel in acid medium: experimental and theoretical approaches. Carbohydr Polym2015;
124: 280–291.
42.
BarthA.Infrared spectroscopy of proteins. Biochim Biophys Acta Bioenerg2007;
1767: 1073–1101.
43.
RathPBouschéOMerrillAR, et al.
Fourier transform infrared evidence for a predominantly alpha-helical structure of the membrane bound channel forming COOH-terminal peptide of colicin E1. Biophys J1991;
59: 516.
44.
NelsonMJSeitzSP.The structure and function of lipoxygenase. Curr Opin Struct Biol1994;
4: 878–884.
45.
DongXLiLZhaoC, et al.
Controllable synthesis of RGO/Fe x O y nanocomposites as high-performance anode materials for lithium ion batteries. J Mater Chem A2014;
2: 9844–9850.
46.
BawaPPillayVChoonaraYE, et al.
A composite polyelectrolytic matrix for controlled oral drug delivery. AAPS Pharm Sci Tech2011;
12: 227–238.
47.
TavakoliNTaymouriSSaeidiA, et al.
Thermosensitive hydrogel containing sertaconazole loaded nanostructured lipid carriers for potential treatment of fungal keratitis. Pharm Dev Technol2019;
24: 891–901.
48.
BlancoMDAlonsoMJ.Development and characterization of protein-loaded poly (lactide-co-glycolide) nanospheres. Eur J Pharm Biopharm1997;
43: 287–294.
49.
PachuauL.Recent developments in novel drug delivery systems for wound healing. Expert Opin Drug Deliv2015;
12: 1895–1909.
50.
HaywardSCilliersTSwartP.Lipoxygenases: from isolation to application. Comprehensive Rev Food Sci Food Safe2017;
16: 199–211.
51.
LuWZhaoXXuZ, et al.
Development of a new colorimetric assay for lipoxygenase activity. Anal Biochem2013;
441: 162–168.
52.
SalehiFBehboudiHKavoosiG, et al.
Oxidative DNA damage induced by ROS-modulating agents with the ability to target DNA: a comparison of the biological characteristics of citrus pectin and apple pectin. Sci Rep2018;
8: 13902.
53.
OpanasopitPApirakaramwongANgawhirunpatT, et al.
Development and characterization of pectinate micro/nanoparticles for gene delivery. AAPS Pharm Sci Tech2008;
9: 67–74.
54.
VermaAKKumarA.Pharmacokinetics and biodistribution of negatively charged pectin nanoparticles encapsulating paclitaxel. Cancer Nanotechnol2013;
4: 99–102.
55.
FülbierASchnabelRMichaelS, et al.
Successful nucleofection of rat adipose-derived stroma cells with Ambystoma mexicanum epidermal lipoxygenase (AmbLOXe). Stem Cell Res Ther2014;
5: 113.
56.
StracciaMCd'AyalaGGRomanoI, et al.
Alginate hydrogels coated with chitosan for wound dressing. Mar Drugs2015;
13: 2890–2908.
57.
ChandaAAdhikariJGhoshA, et al.
Electrospun chitosan/polycaprolactone-hyaluronic acid bilayered scaffold for potential wound healing applications. Int J Biol Macromol2018;
116: 774–785.
58.
FeizabadiFMinaiyanMTaheriA.Arginine functionalized bacterial cellulose nanofibers containing gel as an effective wound dressing: in vitro and in vivo evaluation. Curr Drug Deliv2018;
15: 840–849.
59.
FarokhiMMottaghitalabFFatahiY, et al.
Overview of silk fibroin use in wound dressings. Trends Biotechnol2018;
36: 907–922.
60.
KujathPMichelsenA.Wounds – from physiology to wound dressing. Dtsch Arztebl Int2008;
105: 239.
61.
MiguelSPFigueiraDRSimõesD, et al.
Electrospun polymeric nanofibres as wound dressings: a review. Colloids Surf B Biointerf2018;
169: 60–71.
62.
MurawalaPTanakaEMCurrieJD.Regeneration: the ultimate example of wound healing. Semin Cell Dev Biol2012;
23: 954–962.
