A State-of-the-art Review on Keratin Biomaterial as Eminent Nanocarriers
for Drug Delivery Applications

Venkataramanan      Srinivasan; Ponnusamy      Palanisamy
doi:10.2174/1570180819666220620094943
Abstract

The utilization of biomaterials in the human body was first practiced several years ago to restore normal functional activities by replacing the impaired organs with bio-inspired materials without devastating the cells and tissues. Today, many advanced technologies are reported to be worthwhile to effectively prepare different categories of biomaterials with amplified properties and characteristics for therapeutic applications. When considering the prosperous aspects of biomaterials, keratin has proved to be a fascinating material and has allured many researchers in various novel scientific studies, especially in drug delivery systems. Keratin is a naturally derived fibrous protein with cysteine, proline, serine, and glycine as the main amino acid constituents and has been found to have remarkable properties. Although keratin exhibits excellence and loss of distinction, it is utilized effectively in drug delivery for treating various diseases. Certainly, keratin nanoparticles (KNPs) showed remarkable features, such as optimistic surface area, good encapsulation efficiency, and controlled release of drugs. However, there is a need for more research to know about the cell interaction with keratin nanoparticles in novel drug delivery management. Indeed, certain biological and mechanical factors in alpha and beta keratins are still ambiguous, and higher attentiveness is required. The major purpose of this review is to assess the prospective utility and outstanding features of keratin nanoparticles in drug delivery systems. Keratin types, source of extraction, and properties are reviewed in this article. The characteristics and development of KNP are highlighted. Furthermore, the importance of nanoparticles in drug delivery, drug release mechanisms, challenges, and the need for future research are discussed.
Keywords: Alpha keratin, beta keratin, biomaterials, drug delivery system, keratin nanoparticles, metallic nanoparticles.
[1]
Park, JB; Bronzino, JD Biomaterials: Principles and applications. 2002.

[2]
Adeosun, SO.; Ilomuanya, MO.; Gbenebor, OP.; Dada, MO.; Odili, CC. iomaterials for drug delivery: Sources, classification, synthesis,  processing, and applications. Advanced Functional MaterialsIntechOpen, 2020.

[3]
Fenton, O.S.; Olafson, K.N.; Pillai, P.S.; Mitchell, M.J.; Langer, R. Advances in biomaterials for drug delivery. Adv. Mater.,  2018, 30(29)e1705328
 [http://dx.doi.org/10.1002/adma.201705328] [PMID:  29736981]

[4]
Giannelli, M.; Guerrini, A.; Ballestri, M.; Aluigi, A.; Zamboni, R.; Sotgiu, G.; Posati, T. Bioactive keratin and fibroin nanoparticles: An overview of their preparation strategies. Nanomaterials (Basel),  2022, 12(9), 1406.
 [http://dx.doi.org/10.3390/nano12091406]

[5]
Sharma, S.; Kumar, A. 2019.

[6]
DeFrates, K.; Markiewicz, T.; Gallo, P.; Rack, A.; Weyhmiller, A.; Jarmusik, B.; Hu, X. Protein polymer-based nanoparticles: Fabrication and medical applications. Int. J. Mol. Sci.,  2018, 19(6), 1717.
 [PMID:  29890756] [http://dx.doi.org/10.3390/ijms19061717]

[7]
Yang, G.; Yao, Y.; Wang, X. Comparative study of kerateine and keratose based composite nanofibers for biomedical applications. Mater. Sci. Eng. C,  2018, 83, 1-8.
 [PMID:  29208266] [http://dx.doi.org/10.1016/j.msec.2017.07.057]

[8]
Luo, T.; Hao, S.; Chen, X.; Wang, J.; Yang, Q.; Wang, Y.; Weng, Y.; Wei, H.; Zhou, J.; Wang, B. Development and assessment of kerateine nanoparticles for use as a hemostatic agent. Mater. Sci. Eng. C,  2016, 63, 352-358.
 [PMID:  27040229] [http://dx.doi.org/10.1016/j.msec.2016.03.007]

[9]
Singh, S. Keratin-based materials in Biomedical engineering. IOP Conf. Series Mater. Sci. Eng.,  2021, 1116(1)012024
 [http://dx.doi.org/10.1088/1757-899X/1116/1/012024]

[10]
Reddy, N. Keratin-based Biomaterials and Bioproducts; Smithers Rapra, 2017. 

[11]
Curcio, M.; Blanco-Fernandez, B.; Diaz-Gomez, L.; Concheiro, A.; Alvarez-Lorenzo, C. Hydrophobically modified keratin vesicles for GSH-responsive intracellular drug release. Bioconjug. Chem.,  2015, 26(9), 1900-1907.
 [PMID:  26287808] [http://dx.doi.org/10.1021/acs.bioconjchem.5b00289]

[12]
Li, W.; Gao, F.; Kan, J.; Deng, J.; Wang, B.; Hao, S. Synthesis and fabrication of a keratin-conjugated insulin hydrogel for the enhancement of wound healing. Colloids Surf. B Biointerfaces,  2019, 175, 436-444.
 [PMID:  30562718] [http://dx.doi.org/10.1016/j.colsurfb.2018.12.020]

[13]
Li, Y.; Zhi, X.; Lin, J.; You, X.; Yuan, J. Preparation and characterization of DOX loaded keratin nanoparticles for pH/GSH dual responsive release. Mater. Sci. Eng. C,  2017, 73, 189-197.
 [PMID:  28183597] [http://dx.doi.org/10.1016/j.msec.2016.12.067]

[14]
Tran, C.D.; Prosenc, F.; Franko, M. Facile synthesis, structure, biocompatibility and antimicrobial property of gold nanoparticle composites from cellulose and keratin. J. Colloid Interface Sci.,  2018, 510, 237-245.
 [PMID:  28950170] [http://dx.doi.org/10.1016/j.jcis.2017.09.006]

[15]
Zhang, H.; Pei, M.; Liu, P. Keratin-based drug-protein conjugate with acid-labile and reduction-cleavable linkages in series for tumor intracellular DOX delivery. J. Ind. Eng. Chem.,  2019, 80, 739-748.
 [http://dx.doi.org/10.1016/j.jiec.2019.05.041]

[16]
Peng, Z.; Zhang, J.; Du, G.; Chen, J. Keratin waste recycling based on microbial degradation: Mechanisms and prospects. ACS Sustain. Chem.& Eng.,  2019, 7(11), 9727-9736.
 [http://dx.doi.org/10.1021/acssuschemeng.9b01527]

[17]
Zhang, H.; Su, F.; Ma, X.; Zhao, G. Brief introduction of keratin and its biological application, especially in drug delivery., 2021.

[18]
Krishnan, U.M. Protein and peptide nanostructures for drug and gene delivery.Artificial Protein and Peptide Nanofibers; Woodhead Publishing, 2020, pp. 279-325.

[19]
Shah, A.; Tyagi, S.; Bharagava, R.N.; Belhaj, D.; Kumar, A.; Saxena, G.; Saratale, G.D.; Mulla, S.I. 2019.

[20]
Wang, B.; Yang, W.; McKittrick, J.; Meyers, M.A. Keratin: Structure, mechanical properties, occurrence in biological organisms, and efforts at bioinspiration. Prog. Mater. Sci.,  2016, 76, 229-318.
 [http://dx.doi.org/10.1016/j.pmatsci.2015.06.001]

[21]
Shetty, S.; Gokul, S. Keratinization and its disorders. Oman Med. J.,  2012, 27(5), 348-357.
 [PMID:  23074543] [http://dx.doi.org/10.5001/omj.2012.90]

[22]
Feroz, S.; Muhammad, N.; Ranayake, J.; Dias, G. Keratin - Based materials for biomedical applications. Bioact. Mater.,  2020, 5(3), 496-509.
 [PMID:  32322760] [http://dx.doi.org/10.1016/j.bioactmat.2020.04.007]

[23]
Nakata, R.; Osumi, Y.; Miyagawa, S.; Tachibana, A.; Tanabe, T. Preparation of keratin and chemically modified keratin hydrogels and their evaluation as cell substrate with drug releasing ability. J. Biosci. Bioeng.,  2015, 120(1), 111-116.
 [PMID:  25561327] [http://dx.doi.org/10.1016/j.jbiosc.2014.12.005]

[24]
Moll, R.; Divo, M.; Langbein, L. The human keratins: Biology and pathology. Histochem. Cell Biol.,  2008, 129(6), 705-733.
 [PMID:  18461349] [http://dx.doi.org/10.1007/s00418-008-0435-6]

[25]
Makar, I.A.; Havryliak, V.V.; Sedilo, H.M. Genetic and biochemical aspects of keratin synthesis by hair follicles. Tsitol. Genet.,  2007, 41(1), 75-79.
 [PMID:  17427419] [http://dx.doi.org/10.3103/S0095452707010094]

[26]
Donato, R.K.; Mija, A. Keratin associations with synthetic, biosynthetic and natural polymers: An extensive review. Polymers (Basel),  2019, 12(1), 32.
 [PMID:  31878054] [http://dx.doi.org/10.3390/polym12010032]

[27]
Norell, M.; Ji, Q.; Gao, K.; Yuan, C.; Zhao, Y.; Wang, L. Palaeontology: ‘modern’ feathers on a non-avian dinosaur. Nature,  2002, 416(6876), 36-37.
 [PMID:  11882883] [http://dx.doi.org/10.1038/416036a]

[28]
Bragulla, H.H.; Homberger, D.G. Structure and functions of keratin proteins in simple, stratified, keratinized and cornified epithelia. J. Anat.,  2009, 214(4), 516-559.
 [PMID:  19422428] [http://dx.doi.org/10.1111/j.1469-7580.2009.01066.x]

[29]
Ullah, A.; Vasanthan, T.; Bressler, D.; Elias, A.L.; Wu, J. Bioplastics from feather quill. Biomacromolecules,  2011, 12(10), 3826-3832.
 [PMID:  21888378] [http://dx.doi.org/10.1021/bm201112n]

[30]
Xiao, X.; Hu, J.; Gui, X.; Lu, J.; Luo, H. Is biopolymer hair a multi-responsive smart material? Polym. Chem.,  2017, 8(1), 283-294.
 [http://dx.doi.org/10.1039/C6PY01283C]

[31]
Idris, A.; Vijayaraghavan, R.; Rana, U.A.; Fredericks, D.; Patti, A.F.; Macfarlane, D.R. Dissolution of feather keratin in ionic liquids. Green Chem.,  2013, 15(2), 525-534.
 [http://dx.doi.org/10.1039/C2GC36556A]

[32]
Agarwal, V.; Panicker, A.G.; Indrakumar, S.; Chatterjee, K. Comparative study of keratin extraction from human hair. Int. J. Biol. Macromol.,  2019, 133, 382-390.
 [PMID:  31002909] [http://dx.doi.org/10.1016/j.ijbiomac.2019.04.098]

[33]
Osborne, C.S.; Leitner, I.; Favre, B.; Ryder, N.S. Antifungal drug response in an in vitro model of dermatophyte nail infection. Med. Mycol.,  2004, 42(2), 159-163.
 [PMID:  15124869] [http://dx.doi.org/10.1080/13693780310001656803]

[34]
Khumalo, M.; Tesfaye, T.; Sithole, B. Possible beneficiation of waste chicken feathers via conversion into biomedical applications. Int. J. Chem. Sci.,  2019, 17(1), 29830.

[35]
Guidotti, G.; Soccio, M.; Posati, T.; Sotgiu, G.; Tiboni, M.; Barbalinardo, M.; Valle, F.; Casettari, L.; Zamboni, R.; Lotti, N.; Aluigi, A. Regenerated wool keratin-polybutylene succinate nanofibrous mats for drug delivery and cells culture. Polym. Degrad. Stabil.,  2020, 179109272
 [http://dx.doi.org/10.1016/j.polymdegradstab.2020.109272]

[36]
Danalev, D.; Koleva, M.; Ivanova, D.; Vezenkov, L.; Vassilev, N. Synthesis of two peptide mimetics as markers for chemical changes of wool’s keratin during skin unhairing process. Protein Pept. Lett.,  2008, 15(4), 353-355.
 [http://dx.doi.org/10.2174/092986608784246489]

[37]
Tachibana, A.; Furuta, Y.; Takeshima, H.; Tanabe, T.; Yamauchi, K. Fabrication of wool keratin sponge scaffolds for long-term cell cultivation. J. Biotechnol.,  2002, 93(2), 165-170.
 [PMID:  11738723] [http://dx.doi.org/10.1016/S0168-1656(01)00395-9]

[38]
Bousquet, O.; Ma, L.; Yamada, S.; Gu, C.; Idei, T.; Takahashi, K.; Wirtz, D.; Coulombe, P.A. The nonhelical tail domain of keratin 14 promotes filament bundling and enhances the mechanical properties of keratin intermediate filaments in vitro. J. Cell Biol.,  2001, 155(5), 747-754.
 [PMID:  11724817] [http://dx.doi.org/10.1083/jcb.200104063]

[39]
Meyers, M.A.; Chen, P.Y.; Lin, A.Y.; Seki, Y. Biological materials: Structure and mechanical properties. Prog. Mater. Sci.,  2008, 53(1), 1-206.
 [http://dx.doi.org/10.1016/j.pmatsci.2007.05.002]

[40]
Cameron, G.J.; Wess, T.J.; Bonser, R.H. Young’s modulus varies with differential orientation of keratin in feathers. J. Struct. Biol.,  2003, 143(2), 118-123.
 [http://dx.doi.org/10.1016/S1047-8477(03)00142-4]

[41]
Butler, M.; Johnson, A.S. Are melanized feather barbs stronger? J. Exp. Biol.,  2004, 207(Pt 2), 285-293.
 [PMID:  14668312] [http://dx.doi.org/10.1242/jeb.00746]

[42]
Meyers, M.A.; McKittrick, J. Chen, PY Structural biological materials: Critical mechanics-materials connections. Science,  2013, 339(6121), 773-779.

[43]
Ashby, M.F.; Gibson, L.J.; Wegst, U.; Olive, R. The mechanical properties of natural materials. I. Material property charts. Proc. R. Soc. Lond. A Math. Phys. Sci.,  1938, 1995(450), 123-140.

[44]
Kunchi, C.; Venkateshan, K.C.; Reddy, N.D.; Adusumalli, R.B. Correlation between mechanical and thermal properties of human hair. Int. J. Trichology,  2018, 10(5), 204-210.
 [PMID:  30607039] [http://dx.doi.org/10.4103/ijt.ijt_24_18]

[45]
Yamada, S.; Wirtz, D.; Coulombe, P.A. Pairwise assembly determines the intrinsic potential for self-organization and mechanical properties of keratin filaments. Mol. Biol. Cell,  2002, 13(1), 382-391.
 [PMID:  11809846] [http://dx.doi.org/10.1091/mbc.01-10-0522]

[46]
Chou, C.C.; Buehler, M.J. Structure and mechanical properties of human trichocyte keratin intermediate filament protein. Biomacromolecules,  2012, 13(11), 3522-3532.
 [PMID:  22963508] [http://dx.doi.org/10.1021/bm301254u]

[47]
Flores-Hernández, C.G.; Colin-Cruz, A.; Velasco-Santos, C.; Castaño, V.M.; Almendarez-Camarillo, A.; Olivas-Armendariz, I.; Martínez-Hernández, A.L. Chitosan-starch-keratin composites: Improving thermo-mechanical and degradation properties through chemical modification. J. Polym. Environ.,  2018, 26(5), 2182-2191.
 [http://dx.doi.org/10.1007/s10924-017-1115-1]

[48]
Panorchan, P.; Lee, J.S.; Daniels, B.R.; Kole, T.P.; Tseng, Y.; Wirtz, D. Probing cellular mechanical responses to stimuli using ballistic intracellular nanorheology. Methods Cell Biol.,  2007, 83, 113-140.
 [http://dx.doi.org/10.1016/S0091-679X(07)83006-8]

[49]
Abou El-Kheir, A.; Popescu, C.; Mowafi, S.; Salama, M.; El-Sayed, H. Physico-chemical properties of keratin-polyvinyl alcohol composite. Fibers Polym.,  2015, 16(3), 537-542.
 [http://dx.doi.org/10.1007/s12221-015-0537-4]

[50]
Garrido, T.; Leceta, I.; de la Caba, K.; Guerrero, P. Chicken feathers as a natural source of sulphur to develop sustainable protein films with enhanced properties. Int. J. Biol. Macromol.,  2018, 106, 523-531.
 [PMID:  28801097] [http://dx.doi.org/10.1016/j.ijbiomac.2017.08.043]

[51]
Zhang, Q.; Shan, G.; Cao, P.; He, J.; Lin, Z.; Huang, Y.; Ao, N. Mechanical and biological properties of oxidized horn keratin. Mater. Sci. Eng. C,  2015, 47, 123-134.
 [PMID:  25492180] [http://dx.doi.org/10.1016/j.msec.2014.11.051]

[52]
Kunjiappan, S.; Theivendren, P.; Pavadai, P.; Govindaraj, S.; Sankaranarayanan, M.; Somasundaram, B.; Arunachalam, S.; Ram Kumar Pandian, S.; Ammunje, D.N. Design and in silico modeling of Indoloquinoxaline incorporated keratin nanoparticles for modulation of glucose metabolism in 3T3-L1 adipocytes. Biotechnol. Prog.,  2020, 36(1)e2904
 [PMID:  31496124] [http://dx.doi.org/10.1002/btpr.2904]

[53]
Chilakamarry, CR; Mahmood, S; Saffe, SN; Arifin, MA; Gupta, A; Sikkandar, MY; Begum, SS; Narasaiah, B 2021.

[54]
Sharma, S.; Gupta, A. Sustainable management of keratin waste biomass: Applications and future perspectives. Braz. Arch. Biol. Technol.,  2016, 59(0), 59.
 [http://dx.doi.org/10.1590/1678-4324-2016150684]

[55]
Kim, S.Y.; Wong, A.H.; Abou Neel, E.A.; Chrzanowski, W.; Chan, H.K. The future perspectives of natural materials for pulmonary drug delivery and lung tissue engineering. Expert Opin. Drug Deliv.,  2015, 12(6), 869-887.
 [PMID:  25522669] [http://dx.doi.org/10.1517/17425247.2015.993314]

[56]
Hill, P.; Brantley, H.; Van Dyke, M. Some properties of keratin biomaterials: Kerateines. Biomaterials,  2010, 31(4), 585-593.
 [PMID:  19822360] [http://dx.doi.org/10.1016/j.biomaterials.2009.09.076]

[57]
Katoh, K.; Shibayama, M.; Tanabe, T.; Yamauchi, K. Preparation and physicochemical properties of compression-molded keratin films. Biomaterials,  2004, 25(12), 2265-2272.
 [PMID:  14741591] [http://dx.doi.org/10.1016/j.biomaterials.2003.09.021]

[58]
Thakur, G.; Rodrigues, F.C.; Singh, K. 2018.

[59]
Iqbal, H.M.; Keshavarz, T. Bioinspired polymeric carriers for drug delivery applications., 2018.

[60]
Varanko, A.; Saha, S.; Chilkoti, A. Recent trends in protein and peptide-based biomaterials for advanced drug delivery. Adv. Drug Deliv. Rev.,  2020, 156, 133-187.
 [PMID:  32871201] [http://dx.doi.org/10.1016/j.addr.2020.08.008]

[61]
Ledford, B.; Barron, C.; Van Dyke, M.; He, J.Q. Keratose hydrogel for tissue regeneration and drug delivery.Seminars in Cell & Developmental Biology; Academic Press, 2021. 

[62]
Hashim, A.A. 2012.

[63]
Vega-Vásquez, P.; Mosier, N.S.; Irudayaraj, J. Nanoscale drug delivery systems: From medicine to agriculture. Front. Bioeng. Biotechnol.,  2020, 8, 79.
 [PMID:  32133353] [http://dx.doi.org/10.3389/fbioe.2020.00079]

[64]
Haider, S. Nanoparticles: The future of drug delivery. J. Young Investig.,  2020, 38(1)

[65]
Rizvi, S.A.A.; Saleh, A.M. Applications of nanoparticle systems in drug delivery technology. Saudi Pharm. J.,  2018, 26(1), 64-70.
 [PMID:  29379334] [http://dx.doi.org/10.1016/j.jsps.2017.10.012]

[66]
Deng, Y.; Zhang, X.; Shen, H.; He, Q.; Wu, Z.; Liao, W.; Yuan, M. Application of the nano-drug delivery system in treatment of cardiovascular diseases. Front. Bioeng. Biotechnol.,  2020, 7, 489.
 [PMID:  32083068] [http://dx.doi.org/10.3389/fbioe.2019.00489]

[67]
Patra, J.K.; Das, G.; Fraceto, L.F.; Campos, E.V.R.; Rodriguez-Torres, M.D.P.; Acosta-Torres, L.S.; Diaz-Torres, L.A.; Grillo, R.; Swamy, M.K.; Sharma, S.; Habtemariam, S.; Shin, H.S. Nano based drug delivery systems: Recent developments and future prospects. J. Nanobiotechnology,  2018, 16(1), 71.
 [PMID:  30231877] [http://dx.doi.org/10.1186/s12951-018-0392-8]

[68]
Mirza, A.Z.; Siddiqui, F.A. Nanomedicine and drug delivery: A mini review. Int. Nano Lett.,  2014, 4(1), 94.
 [http://dx.doi.org/10.1007/s40089-014-0094-7]

[69]
Suri, S.S.; Fenniri, H.; Singh, B. Nanotechnology-based drug delivery systems. J. Occup. Med. Toxicol.,  2007, 2(1), 16.
 [PMID:  18053152] [http://dx.doi.org/10.1186/1745-6673-2-16]

[70]
De Jong, W.H.; Borm, P.J. Drug delivery and nanoparticles: applications and hazards. Int. J. Nanomedicine,  2008, 3(2), 133-149.
 [PMID:  18686775] [http://dx.doi.org/10.2147/IJN.S596]

[71]
Mitchell, M.J.; Billingsley, M.M.; Haley, R.M.; Wechsler, M.E.; Peppas, N.A.; Langer, R. Engineering precision nanoparticles for drug delivery. Nat. Rev. Drug Discov.,  2021, 20(2), 101-124.
 [PMID:  33277608] [http://dx.doi.org/10.1038/s41573-020-0090-8]

[72]
Lombardo, D.; Kiselev, M.A.; Caccamo, M.T. 2019.

[73]
Chavanpatil, M.D.; Khdair, A.; Panyam, J. Nanoparticles for cellular drug delivery: Mechanisms and factors influencing delivery. J. Nanosci. Nanotechnol.,  2006, 6(9-10), 2651-2663.
 [PMID:  17048473] [http://dx.doi.org/10.1166/jnn.2006.443]

[74]
Hans, M.L.; Lowman, A.M. Biodegradable nanoparticles for drug delivery and targeting. Curr. Opin. Solid State Mater. Sci.,  2002, 6(4), 319-327.
 [http://dx.doi.org/10.1016/S1359-0286(02)00117-1]

[75]
Kawashima, Y.; Yamamoto, H.; Takeuchi, H.; Fujioka, S.; Hino, T. Pulmonary delivery of insulin with nebulized DL-lactide/glycolide copolymer (PLGA) nanospheres to prolong hypoglycemic effect. J. Control. Release,  1999, 62(1-2), 279-287.
 [http://dx.doi.org/10.1016/S0168-3659(99)00048-6]

[76]
Zhang, C.; Zhao, L.; Dong, Y.; Zhang, X.; Lin, J.; Chen, Z. Folate-mediated poly (3-hydroxybutyrate-co-3-hydroxyoctanoate) nanoparticles for targeting drug delivery. Eur. J. Pharm. Biopharm.,  2010, 76(1), 10-16.
 [PMID:  20472060] [http://dx.doi.org/10.1016/j.ejpb.2010.05.005]

[77]
Bhatia, S. Nanoparticles types, classification, characterization, fabrication methods and drug delivery applications. InNatural polymer drug delivery systems; Springer: Cham, 2016, pp. 33-93.

[78]
Kunjiappan, S.; Pavadai, P.; Vellaichamy, S.; Ram Kumar Pandian, S.; Ravishankar, V.; Palanisamy, P.; Govindaraj, S.; Srinivasan, G.; Premanand, A.; Sankaranarayanan, M.; Theivendren, P. Surface receptor-mediated targeted drug delivery systems for enhanced cancer treatment: A state-of-the-art review. Drug Dev. Res.,  2021, 82(3), 309-340.
 [PMID:  33170541] [http://dx.doi.org/10.1002/ddr.21758]

[79]
Maiti, S. Sen, KK Introductory chapter: Drug delivery concepts; Adv Technol Deliv Ther, 2017, pp. 1-2.

[80]
Bazak, R.; Houri, M.; Achy, S.E.; Hussein, W.; Refaat, T. Passive targeting of nanoparticles to cancer: A comprehensive review of the literature. Mol. Clin. Oncol.,  2014, 2(6), 904-908.
 [PMID:  25279172] [http://dx.doi.org/10.3892/mco.2014.356]

[81]
Patel, J.K.; Patel, A.P. Passive targeting of nanoparticles to cancer. InSurface Modification of Nanoparticles for Targeted Drug Delivery; Springer: Cham, 2019, pp. 125-143.

[82]
Clemons, T.D.; Singh, R.; Sorolla, A.; Chaudhari, N.; Hubbard, A.; Iyer, K.S. Distinction between active and passive targeting of nanoparticles dictate their overall therapeutic efficacy. Langmuir,  2018, 34(50), 15343-15349.
 [PMID:  30441895] [http://dx.doi.org/10.1021/acs.langmuir.8b02946]

[83]
Rosenblum, D.; Joshi, N.; Tao, W.; Karp, J.M.; Peer, D. Progress and challenges towards targeted delivery of cancer therapeutics. Nat. Commun.,  2018, 9(1), 1410.
 [PMID:  29650952] [http://dx.doi.org/10.1038/s41467-018-03705-y]

[84]
Bazak, R.; Houri, M.; El Achy, S.; Kamel, S.; Refaat, T. Cancer active targeting by nanoparticles: A comprehensive review of literature. J. Cancer Res. Clin. Oncol.,  2015, 141(5), 769-784.
 [PMID:  25005786] [http://dx.doi.org/10.1007/s00432-014-1767-3]

[85]
Attia, M.F.; Anton, N.; Wallyn, J.; Omran, Z.; Vandamme, T.F. An overview of active and passive targeting strategies to improve the nanocarriers efficiency to tumour sites. J. Pharm. Pharmacol.,  2019, 71(8), 1185-1198.
 [PMID:  31049986] [http://dx.doi.org/10.1111/jphp.13098]

[86]
Kumar Khanna, V. Targeted delivery of nanomedicines., 2012.

[87]
Pearce, A.K.; O’Reilly, R.K. Insights into active targeting of nanoparticles in drug delivery: Advances in clinical studies and design considerations for cancer nanomedicine. Bioconjug. Chem.,  2019, 30(9), 2300-2311.
 [PMID:  31441642] [http://dx.doi.org/10.1021/acs.bioconjchem.9b00456]

[88]
Amini, S.; Salehi, H.; Setayeshmehr, M.; Ghorbani, M. Natural and synthetic polymeric scaffolds used in peripheral nerve tissue engineering: Advantages and disadvantages. Polym. Adv. Technol.,  2021, 32(6), 2267-2289.
 [http://dx.doi.org/10.1002/pat.5263]

[89]
Varma, G.G.; Sonawane, P.R. 

[90]
Han, S.; Ham, T.R.; Haque, S.; Sparks, J.L.; Saul, J.M. Alkylation of human hair keratin for tunable hydrogel erosion and drug delivery in tissue engineering applications. Acta Biomater.,  2015, 23, 201-213.
 [PMID:  25997587] [http://dx.doi.org/10.1016/j.actbio.2015.05.013]

[91]
Muhamad, I.I.; Selvakumaran, S.; Lazim, N.A. Designing polymeric nanoparticles for targeted drug delivery system. Nanomed.,  2014, 287, 287.

[92]
Sharma, L.A.; Love, R.M. 

[93]
Vasconcelos, A.; Cavaco-Paulo, A. The use of keratin in biomedical applications. Curr. Drug Targets,  2013, 14(5), 612-619.
 [PMID:  23410124] [http://dx.doi.org/10.2174/1389450111314050010]

[94]
Shavandi, A.; Silva, T.H.; Bekhit, A.A.; Bekhit, A.E.A. Keratin: Dissolution, extraction and biomedical application. Biomater. Sci.,  2017, 5(9), 1699-1735.
 [PMID:  28686242] [http://dx.doi.org/10.1039/C7BM00411G]

[95]
Du, J.; Wu, Q.; Li, Y.; Liu, P.; Han, X.; Wang, L.; Yuan, J.; Meng, X.; Xiao, Y. Preparation and characterization of Keratin-PEG conjugate-based micelles as a tumor microenvironment-responsive drug delivery system. J. Biomater. Sci. Polym. Ed.,  2020, 31(9), 1163-1178.
 [PMID:  32204684] [http://dx.doi.org/10.1080/09205063.2020.1747044]

[96]
Nanthavanan, P.; Arungandhi, K.; Sunmathi, D.; Niranjana, J. Biological synthesis of keratin nanoparticles from dove feather (Columba livia) and its applications. Asian J. Pharm. Clin. Res.,  2019, 12(10), 142-146.
 [http://dx.doi.org/10.22159/ajpcr.2019.v12i10.34572]

[97]
Liebeck, B.M.; Hidalgo, N.; Roth, G.; Popescu, C.; Böker, A. Synthesis and characterization of methyl cellulose/keratin hydrolysate composite membranes. Polymers (Basel),  2017, 9(3), 91.
 [PMID:  30970770] [http://dx.doi.org/10.3390/polym9030091]

[98]
Van Gheluwe, L.; Chourpa, I.; Gaigne, C.; Munnier, E. Polymer-based smart drug delivery systems for skin application and demonstration of stimuli-responsiveness. Polymers (Basel),  2021, 13(8), 1285.
 [PMID:  33920816] [http://dx.doi.org/10.3390/polym13081285]

[99]
Saha, S.; Arshad, M.; Zubair, M.; Ullah, A. Keratin as a Biopolymer. InKeratin as a Protein Biopolymer; Springer: Cham, 2019, pp. 163-185.

[100]
Jin, M.; Wang, J.; Chu, M.X.; Piao, J.; Piao, J.A.; Zhao, F.Q. The study on biological function of keratin 26, a novel member of Liaoning cashmere goat keratin gene family. PLoS One,  2016, 11(12)e0168015
 [PMID:  27997570] [http://dx.doi.org/10.1371/journal.pone.0168015]

[101]
Lee, H.; Noh, K.; Lee, S.C.; Kwon, I.K.; Han, D.W.; Lee, I.S.; Hwang, Y.S. Human hair keratin and its-based biomaterials for biomedical applications. Tissue Eng. Regen. Med.,  2014, 11(4), 255-265.
 [http://dx.doi.org/10.1007/s13770-014-0029-4]

[102]
Dou, Y.; Zhang, B.; He, M.; Yin, G.; Cui, Y.; Savina, I.N. Keratin/polyvinyl alcohol blend films cross-linked by dialdehyde starch and their potential application for drug release. Polymers (Basel),  2015, 7(3), 580-591.
 [http://dx.doi.org/10.3390/polym7030580]

[103]
Wang, J.; Hao, S.; Luo, T.; Yang, Q.; Wang, B. Development of feather keratin nanoparticles and investigation of their hemostatic efficacy. Mater. Sci. Eng. C,  2016, 68, 768-773.
 [PMID:  27524078] [http://dx.doi.org/10.1016/j.msec.2016.07.035]

[104]
Guo, T.; Yang, X.; Deng, J.; Zhu, L.; Wang, B.; Hao, S. Keratin nanoparticles-coating electrospun PVA nanofibers for potential neural tissue applications. J. Mater. Sci. Mater. Med.,  2018, 30(1), 9.
 [PMID:  30594975] [http://dx.doi.org/10.1007/s10856-018-6207-5]

[105]
Kunjiappan, S.; Panneerselvam, T.; Prasad, P.; Sukumaran, S.; Somasundaram, B.; Sankaranarayanan, M.; Murugan, I.; Parasuraman, P. Design, graph theoretical analysis and in silico modeling of Dunaliella bardawil biomass encapsulated keratin nanoparticles: A scaffold for effective glucose utilization. Biomed. Mater.,  2018, 13(4)045012
 [PMID:  29727301] [http://dx.doi.org/10.1088/1748-605X/aabcea]

[106]
Zhi, X.; Wang, Y.; Li, P.; Yuan, J.; Shen, J. Preparation of keratin/chlorhexidine complex nanoparticles for long-term and dual stimuli-responsive release. RSC Advances,  2015, 5(100), 82334-82341.
 [http://dx.doi.org/10.1039/C5RA16253J]

[107]
Zhai, M.; Xu, Y.; Zhou, B.; Jing, W. Keratin-chitosan/n-ZnO nanocomposite hydrogel for antimicrobial treatment of burn wound healing: Characterization and biomedical application. J. Photochem. Photobiol. B,  2018, 180, 253-258.
 [PMID:  29476966] [http://dx.doi.org/10.1016/j.jphotobiol.2018.02.018]

[108]
Shanmugasundaram, O.L.; Syed Zameer Ahmed, K.; Sujatha, K.; Ponnmurugan, P.; Srivastava, A.; Ramesh, R.; Sukumar, R.; Elanithi, K. Fabrication and characterization of chicken feather keratin/polysaccharides blended polymer coated nonwoven dressing materials for wound healing applications. Mater. Sci. Eng. C,  2018, 92, 26-33.
 [PMID:  30184750] [http://dx.doi.org/10.1016/j.msec.2018.06.020]

[109]
Kunjiappan, S.; Chowdhury, A.; Somasundaram, B.; Bhattacharjee, C.; Periyasamy, S. Optimization, preparation and characterization of rutin-quercetin dual drug loaded keratin nanoparticles for biological applications. Nanomed. J.,  2016, 3(4), 253-267.

[110]
Gao, C.; Zhao, K.; Lin, L.; Wang, J.; Liu, Y.; Zhu, P. Preparation and characterization of biomimetic hydroxyapatite nanocrystals by using partially hydrolyzed keratin as template agent. Nanomaterials (Basel),  2019, 9(2), 241.
 [PMID:  30754714] [http://dx.doi.org/10.3390/nano9020241]

[111]
Mousavi, S.Z.; Manteghian, M.; Shojaosadati, S.A.; Pahlavanzadeh, H. Preparation and characterization of magnetic keratin nanocomposite. Mater. Chem. Phys.,  2018, 215, 40-45.
 [http://dx.doi.org/10.1016/j.matchemphys.2018.05.003]

[112]
Mody, V.V.; Siwale, R.; Singh, A.; Mody, H.R. Introduction to metallic nanoparticles. J. Pharm. Bioallied Sci.,  2010, 2(4), 282-289.
 [PMID:  21180459] [http://dx.doi.org/10.4103/0975-7406.72127]

[113]
Yaqoob, A.A.; Ahmad, H.; Parveen, T.; Ahmad, A.; Oves, M.; Ismail, I.M.I.; Qari, H.A.; Umar, K.; Mohamad Ibrahim, M.N. Recent advances in metal decorated nanomaterials and their various biological applications: A review. Front Chem.,  2020, 8, 341.
 [PMID:  32509720] [http://dx.doi.org/10.3389/fchem.2020.00341]

[114]
He, M.; Chen, M.; Dou, Y.; Ding, J.; Yue, H.; Yin, G.; Chen, X.; Cui, Y. Electrospun silver nanoparticles-embedded feather keratin/poly (vinyl alcohol)/poly (ethylene oxide) antibacterial composite nanofibers. Polymers (Basel),  2020, 12(2), 305.
 [PMID:  32028586] [http://dx.doi.org/10.3390/polym12020305]

[115]
Zhang, Q.; Hu, C.; Yan, K. Preparation and characterization of silver nanoparticles from the super-heated water degraded keratin solutions. J. Nanosci. Nanotechnol.,  2015, 15(9), 6790-6797.
 [PMID:  26716245] [http://dx.doi.org/10.1166/jnn.2015.10486]

[116]
Martin, J.J.; Cardamone, J.M.; Irwin, P.L.; Brown, E.M. Keratin capped silver nanoparticles--synthesis and characterization of a nanomaterial with desirable handling properties. Colloids Surf. B Biointerfaces,  2011, 88(1), 354-361.
 [PMID:  21831609] [http://dx.doi.org/10.1016/j.colsurfb.2011.07.013]

[117]
Konop, M.; Czuwara, J.; Kłodzińska, E.; Laskowska, A.K.; Sulejczak, D.; Damps, T.; Zielenkiewicz, U.; Brzozowska, I.; Sureda, A.; Kowalkowski, T.; Schwartz, R.A.; Rudnicka, L. Evaluation of keratin biomaterial containing silver nanoparticles as a potential wound dressing in full-thickness skin wound model in diabetic mice. J. Tissue Eng. Regen. Med.,  2020, 14(2), 334-346.
 [PMID:  31825159] [http://dx.doi.org/10.1002/term.2998]

[118]
Lü, X.; Cui, S. Wool keratin-stabilized silver nanoparticles. Bioresour. Technol.,  2010, 101(12), 4703-4707.
 [PMID:  20163959] [http://dx.doi.org/10.1016/j.biortech.2010.01.110]

[119]
Wang, Y.; Li, P.; Xiang, P.; Lu, J.; Yuan, J.; Shen, J. Electrospun polyurethane/keratin/AgNP biocomposite mats for biocompatible and antibacterial wound dressings. J. Mater. Chem. B Mater. Biol. Med.,  2016, 4(4), 635-648.
 [PMID:  32262945] [http://dx.doi.org/10.1039/C5TB02358K]

[120]
Madapally, V.D. 2019.

[121]
Thilagam, R.; Gnanamani, A. Preparation, characterization and stability assessment of keratin and albumin functionalized gold nanoparticles for biomedical applications. Appl. Nanosci.,  2020, 10(6), 1-4.
 [http://dx.doi.org/10.1007/s13204-020-01250-z]

[122]
Gupta, S.; Singh, S.P.; Singh, R. Synergistic effect of reductase and keratinase for facile synthesis of protein-coated gold nanoparticles. J. Microbiol. Biotechnol.,  2015, 25(5), 612-619.
 [PMID:  25502826] [http://dx.doi.org/10.4014/jmb.1411.11022]

[123]
Annesi, F.; Pane, A.; Pezzi, L.; Pagliusi, P.; Losso, M.A.; Stamile, B.; Qualtieri, A.; Desiderio, G.; Contardi, M.; Athanassiou, A.; Perotto, G.; De Sio, L. Biocompatible and biomimetic keratin capped Au nanoparticles enable the inactivation of mesophilic bacteria via photo-thermal therapy. Colloids Surf. A Physicochem. Eng. Asp.,  2021, 625126950
 [http://dx.doi.org/10.1016/j.colsurfa.2021.126950]

[124]
Shankar, S.; Rhim, J.W. Eco-friendly antimicrobial nanoparticles of keratin-metal ion complex. Mater. Sci. Eng. C,  2019, 105110068
 [PMID:  31546417] [http://dx.doi.org/10.1016/j.msec.2019.110068]

[125]
Li, Y.; Cao, Y.; Wei, L.; Wang, J.; Zhang, M.; Yang, X.; Wang, W.; Yang, G. The assembly of protein-templated gold nanoclusters for enhanced fluorescence emission and multifunctional applications. Acta Biomater.,  2020, 101, 436-443.
 [PMID:  31672583] [http://dx.doi.org/10.1016/j.actbio.2019.10.035]

[126]
Recent advances in novel drug carrier systems.Tech; Sezer, A.D., Ed.; Open: London, UK, 2012. 

[127]
Almutairi, F.M. Biopolymer Nanoparticles: A Review of Prospects for Application as Carrier for Therapeutics and Diagnostics., 2019.

[128]
Liu, P.; Wu, Q.; Li, Y.; Li, P.; Yuan, J.; Meng, X.; Xiao, Y. DOX-Conjugated keratin nanoparticles for pH-Sensitive drug delivery. Colloids Surf. B Biointerfaces,  2019, 181, 1012-1018.
 [PMID:  31382328] [http://dx.doi.org/10.1016/j.colsurfb.2019.06.057]

[129]
Sun, Z.; Yi, Z.; Zhang, H.; Ma, X.; Su, W.; Sun, X.; Li, X. Bio-responsive alginate-keratin composite nanogels with enhanced drug loading efficiency for cancer therapy. Carbohydr. Polym.,  2017, 175, 159-169.
 [PMID:  28917852] [http://dx.doi.org/10.1016/j.carbpol.2017.07.078]

[130]
Xu, H.; Shi, Z.; Reddy, N.; Yang, Y. Intrinsically water-stable keratin nanoparticles and their in vivo biodistribution for targeted delivery. J. Agric. Food Chem.,  2014, 62(37), 9145-9150.
 [PMID:  25174826] [http://dx.doi.org/10.1021/jf502242h]

[131]
Li, Y.; Lin, J.; Zhi, X.; Li, P.; Jiang, X.; Yuan, J. Triple stimuli-responsive keratin nanoparticles as carriers for drug and potential nitric oxide release. Mater. Sci. Eng. C,  2018, 91, 606-614.
 [PMID:  30033293] [http://dx.doi.org/10.1016/j.msec.2018.05.073]

[132]
Zhi, X.; Liu, P.; Li, Y.; Li, P.; Yuan, J.; Lin, J. One-step fabricated keratin nanoparticles as pH and redox-responsive drug nanocarriers. J. Biomater. Sci. Polym. Ed.,  2018, 29(15), 1920-1934.
 [PMID:  30183550] [http://dx.doi.org/10.1080/09205063.2018.1519987]

[133]
Posati, T.; Giuri, D.; Nocchetti, M.; Sagnella, A.; Gariboldi, M.; Ferroni, C.; Sotgiu, G.; Varchi, G.; Zamboni, R.; Aluigi, A. Keratin-hydrotalcites hybrid films for drug delivery applications. Eur. Polym. J.,  2018, 105, 177-185.
 [http://dx.doi.org/10.1016/j.eurpolymj.2018.05.030]

[134]
Aluigi, A.; Ballestri, M.; Guerrini, A.; Sotgiu, G.; Ferroni, C.; Corticelli, F.; Gariboldi, M.B.; Monti, E.; Varchi, G. Organic solvent-free preparation of keratin nanoparticles as doxorubicin carriers for antitumour activity. Mater. Sci. Eng. C,  2018, 90, 476-484.
 [PMID:  29853116] [http://dx.doi.org/10.1016/j.msec.2018.04.088]

[135]
Gaio, E.; Guerrini, A.; Ballestri, M.; Varchi, G.; Ferroni, C.; Martella, E.; Columbaro, M.; Moret, F.; Reddi, E. Keratin nanoparticles co-delivering Docetaxel and Chlorin e6 promote synergic interaction between chemo- and photo-dynamic therapies. J. Photochem. Photobiol. B,  2019, 199111598
 [PMID:  31465971] [http://dx.doi.org/10.1016/j.jphotobiol.2019.111598]

[136]
Martella, E.; Ferroni, C.; Guerrini, A.; Ballestri, M.; Columbaro, M.; Santi, S.; Sotgiu, G.; Serra, M.; Donati, D.M.; Lucarelli, E.; Varchi, G.; Duchi, S. Functionalized keratin as nanotechnology-based drug delivery system for the pharmacological treatment of osteosarcoma. Int. J. Mol. Sci.,  2018, 19(11), 3670.
 [PMID:  30463350] [http://dx.doi.org/10.3390/ijms19113670]

[137]
Avancini, G.; Guerrini, A.; Ferroni, C.; Tedesco, D.; Ballestri, M.; Columbaro, M.; Menilli, L.; Reddi, E.; Costa, R.; Leanza, L.; Varchi, G.; Moret, F. Keratin nanoparticles and photodynamic therapy enhance the anticancer stem cells activity of salinomycin. Mater. Sci. Eng. C,  2021, 122111899
 [PMID:  33641902] [http://dx.doi.org/10.1016/j.msec.2021.111899]

[138]
Pasut, G. Grand challenges in nano-based drug delivery. Front. Med. Technol.,  2019, 1, 1.
 [PMID:  35047870] [http://dx.doi.org/10.3389/fmedt.2019.00001]

[139]
Prabhakar, P.; Banerjee, M. Nanotechnology in drug delivery system: Challenges and opportunities. J. Pharmaceut. Sci. Res.,  2020, 12(4), 492-498.

[140]
Hamid, R.; Manzoor, I. , 2020. 

[141]
Yetisgin, A.A.; Cetinel, S.; Zuvin, M.; Kosar, A.; Kutlu, O. Therapeutic nanoparticles and their targeted delivery applications. Molecules,  2020, 25(9), 2193.
 [PMID:  32397080] [http://dx.doi.org/10.3390/molecules25092193]

[142]
Kroll, A.; Pillukat, M.H.; Hahn, D.; Schnekenburger, J. Current in vitro methods in nanoparticle risk assessment: Limitations and challenges. Eur. J. Pharm. Biopharm.,  2009, 72(2), 370-377.
 [PMID:  18775492] [http://dx.doi.org/10.1016/j.ejpb.2008.08.009]

[143]
Mirza, Z.; Karim, S. , 2021. 

[144]
Cho, E.J.; Holback, H.; Liu, K.C.; Abouelmagd, S.A.; Park, J.; Yeo, Y. Nanoparticle characterization: State of the art, challenges, and emerging technologies. Mol. Pharm.,  2013, 10(6), 2093-2110.
 [PMID:  23461379] [http://dx.doi.org/10.1021/mp300697h]

[145]
Couvreur, P. Nanoparticles in drug delivery: Past, present and future. Adv. Drug Deliv. Rev.,  2013, 65(1), 21-23.
 [PMID:  22580334] [http://dx.doi.org/10.1016/j.addr.2012.04.010]
Rights & Permissions Print Cite
Article Metrics
3
Explore Articles
Open Access
Open Access Articles
DOI https://dx.doi.org/10.2174/1570180819666220620094943	Print ISSN 1570-1808
Publisher Name Bentham Science Publisher	Online ISSN 1875-628X
Letters in Drug Design & Discovery

A State-of-the-art Review on Keratin Biomaterial as Eminent Nanocarriers for Drug Delivery Applications

Abstract

Graphical Abstract

Letters in Drug Design & Discovery

A State-of-the-art Review on Keratin Biomaterial as Eminent Nanocarriers for Drug Delivery Applications

Abstract Play Pause

Graphical Abstract

Abstract
