Excipients, drug release mechanism and physicochemical characterization methods of Solid lipid nanoparticles
From last thirty years, solid lipid nanoparticles (SLNs) gain much importance as drug delivery vehicle for enhanced delivery of the drugs, proteins, nutraceuticals and cosmetics. SLNs defined as a submicron size range nanoparticle with below 1000 nm and are mainly composed of lipids and surfactants, capable of incorporating both lipophilic and hydrophilic drugs. SLNs also used as controlled systems, targeted delivery and altered therapeutic efficacy purpose. A wide variety of methods such as double emulsion, solvent evaporation, ultra sonication, high-pressure homogenization and microemulsion used for SLNs production. This review provides the significance of SLNs in drug delivery with highlighting on selection of excipients, drug release mechanism, principles and limitations associated with their physicochemical and surface morphological characterization.
Keywords: Solid lipid nanoparticles, enhanced delivery, preparation, characterization, application.
2. Dudhipala N. A Comprehensive Review on Solid Lipid Nanoparticles as Delivery Vehicle for Enhanced Pharmacokinetic and Pharmacodynamic Activity of Poorly Soluble Drugs. Int J Pharm Sci Nanotech. 2019; 12:4421-40.
3. Müller, R.H., Mäder, K., Gohla, S. Solid lipid nanoparticles (SLN) for controlled drug delivery a review of the state of the art. Eur J Pharm Biopharm. 2000; 50:161-177.
4. Scheffel U., B.A. Rhodes, T.K. Natajaran, H.N. Wagner Jr., Albumin microspheres for study of the reticuloendothelial system , J. Nucl. Med. 1970; 13: 498–503.
5. Smith A., Hunneyball I.M. Evaluation of poly(lactic acid) as a biodegradable drug delivery system for parenteral administration. International Journal of Pharmaceutics, 1986; 30:215-220.
6. Mehnert, W., Mäder, K. Solid lipid nanoparticles production, characterization and applications. Adv Drug Deliv Rev. 2012; 64:83-101.
7. Mei Z, Chen H, Weng T, et al. Solid lipid nanoparticle and microemulsion for topical delivery of triptolide. Eur J Pharm Biopharm, 2003; 56:189–96.
8. Gasco MR. Method for producing solid lipid microspheres having a narrow size distribution. United States Patent, 1993, USS 188837.
9. Müller R.H., Mehnert W., Lucks J.S., Schwarz .C, ZurMühlen A., Weyhers H., Freitas C., Ruhl D. Solid lipid nanoparticles (SLN)—An alternative colloidal carrier system for controlled drug delivery. European Journal of Pharmaceutics and Biopharmaceutics, 1995; 41:62–69.
10. Müller RH, Keck CM. Challenges and solutions for the delivery of biotech drugs – a review of drug nanocrystal technology and lipid nanoparticles. J Biotech, 2004; 113:151–70.
11. Dudhipala N. Influence of Solid Lipid Nanoparticles on pharmacodynamic Activity of Poorly Oral Bioavailable Drugs. International Journal of Pharmaceutical Sciences and Nanotechnology. 2020 Jul 11; 13(4):4979-83.
12. Müller RH. Colloidal carriers for controlled drug delivery and targeting: Modification, characterization and in vivo distribution. Taylor & Francis; 1991.
13. Fasano A. Innovative strategies for the oral delivery of drugs and peptides. Trends in biotechnology. 1998 Apr 1; 16(4):152-7.
14. Doodipala R. A review of novel formulation strategies to enhance oral delivery of zaleplon. J Bioequvi avail. 2016; 8(5):211-213.
15. Rajitha R, Narendar D, Arjun N, Mahipal D and Nagaraj B. Colon delivery of naproxen: preparation, characterization and in vivo evaluation. IJPSN, 2016; 9(3):1-10.
16. Plapied L, Duhem N, des Rieux A, Préat V. Fate of polymeric nanocarriers for oral drug delivery. Current opinion in colloid & interface science. 2011 Jun 1; 16(3):228-37.
17. Alekya T, Narendar D, Mahipal D, Arjun N, Nagaraj B. Design and evaluation of chronomodulated drug delivery of tramadol hydrochloride. Drug research. 2018 Mar; 68(03):174-80.
18. Thanki K, Gangwal RP, Sangamwar AT, Jain S. Oral delivery of anticancer drugs: challenges and opportunities. Journal of controlled release. 2013 Aug 28; 170(1):15-40.
19. Narendar D, Arjun N, Sunitha K, Harika K, Nagaraj B. Development of osmotically controlled oral drug delivery systems of tramadol hydrochloride: effect of formulation variables on in-vitro release kinetics. Asian J Pharm. 2016; 10(3):1-10.
20. Arjun N, Narendar D, Sunitha K, Harika K, Madhusudan Rao Y and Nagaraj B. Development, evaluation and influence of formulation and process variables on in vitro performance of oral elementary osmotic device of atenolol. Int J Pharm Invest, 2016; 6(4):1-9.
21. Andrew J. Humberstone, William N. Charman. Lipid-based vehicles for the oral delivery of poorly water soluble drugs. Advanced Drug Delivery Reviews 1997; 25:103- 128.
22. Dudhipala N. Influence of Solid Lipid Nanoparticles on Pharmaco-dynamic Activity of Poorly Oral Bioavailable Drugs. International Journal of Pharmaceutical Sciences and Nanotechnology. 2020 Jul 11; 13(4):4979-83.
23. Damgé C., Michel C., Aprahamian M. Nanocapsules as carriers for oral peptide delivery. Journal of Controlled Release, 1990; 13:233–239.
24. Narendar D and Kishan V. Candesartan cilexetil nanoparticles for improved oral bioavailability. Ther deli, 2017; 8(2):79-88.
25. Florence AT. The oral absorption of micro-and nanoparticulates: neither exceptional nor unusual. Pharm Res 1997; 14:259-66.
26. Ettireddy S, Dudhipala N. Influence of β-Cyclodextrin and Hydroxypropyl-β-Cyclodextrin on Enhancement of Solubility and Dissolution of Isradipine. Int J Pharma Sci and Nanotech. 2017; 10(3):3752-7.
27. Palem CR, Reddy ND, Satyanarayana G, Varsha BP. Development and optimization of Atorvastatin calcium-cyclodextrin inclusion complexed oral disintegrating tablets for enhancement of solubility, dissolution, pharmacokinetic and pharmacodynamic activity by central composite design. Int J Pharm Sci Nanotech 2016; 9(2): 1-11.
28. Butreddy A, Narendar D. Enhancement of solubility and dissolution rate of trandolapril sustained release matrix tablets by liquisolid compact approach. Asian J Pharm 2015; 9 (4):290-297.
29. Palem CR, Gannu R, Narender D, Vamshi Vishnu Yamsani, and Madhusudan Rao Yamsani. Transmucosal Delivery of Domperidone from Bilayered Buccal Patches: In Vitro, Ex Vivo and In Vivo Characterization. Arch Pharm Res. 2011; 34(10):1701-1710.
30. Chinna Reddy Palem, Narendar D, Sunil Kumar Battu, Michael A. Repka and Madhusudan Rao Yamsani. Development, Optimization and in vivo Characterization of Domperidone Controlled Release Hot Melt Extruded Films for Buccal Delivery. Drug Dev Ind Pharm, 2016; 42(3):473-484.
31. Chinna Reddy Palem, Narendar D, Sunil Kumar Battu, Satyanarayana Goda, and Madhusudan Rao Yamsani. Combined dosage form of pioglitazone and felodipine as mucoadhesive pellets via hot melt extrusion for improved buccal delivery with application of quality by design approach. J Drug Del Sci Tech. 2015; 30:209-219.
32. Narendar D, Arjun N and Ramesh B. Recent Updates in the Formulation Strategies to Enhance the Bioavailability of Drugs Administered via Intranasal Route. J bioequ avail. 2016; 8(5):204-207.
33. Reddy, N.D., Chinna R. P., Sunil, R., & & Madhusudan, R. Y. Development of floating matrix tablets of Ofloxacin and Ornidazole in combined dosage form: in vitro and in vivo evaluation in healthy human volunteers. Int J Drug Deli, 2012; 4:462-469.
34. Reddy AB, Reddy ND. Development of multiple-unit floating drug delivery system of clarithromycin: formulation, in vitro dissolution by modified dissolution apparatus, in vivo radiographic studies in human volunteers. Drug research. 2017 Jul; 67(07):412-8.
35. Dudipala R, Palem, C.R., Reddy, S., & Rao, Y.M. Pharmaceutical development and clinical pharmacokinetic evaluation of gastroretentive floating matrix tablets of levofloxacin. Int J Pharma Sci and Nanotech, 2011; 4(3):1461-1467.
36. Narendar D, K. Someshwar, N. Arjun and Y. Madhusudan Rao. Quality by design approach for development and optimization of Quetiapine Fumarate effervescent floating matrix tablets for improved oral delivery. J Pharm Investigation., 2016; 46(3):253-263.
37. Donthi MR, Dudhipala NR, Komalla DR, Suram D, Banala N. Preparation and Evaluation of Fixed Combination of Ketoprofen Enteric Coated and Famotidine Floating Mini Tablets by Single Unit Encapsulation System. Journal of Bioequivalence & Bioavailability. 2015; 7(6):279.
38. Donthi MR, Dudipala N, Komalla DR, Suram D, Banala N. Design and Evaluation of Floating Multi Unit Mini Tablets (MUMTS) Muco Adhesive Drug Delivery System of Famotidine to Treat Upper Gastro Intestinal Ulcers. Journal of Pharmacovigilance. 2015 Oct 12.
39. Banala N, Peddapalli H, Dudhipala N, Chinnala KM. Transmucosal Delivery of Duloxetine Hydrochloride for Prolonged Release: Preparation, in vitro, ex vivo Characteri-zation and in vitro-ex vivo Correlation. International Journal of Pharmaceutical Sciences and Nanotechnology. 2018 Sep 30; 11(5):4249-58.
40. Narendar D, Arjun N, Karthik Yadav J and Ramesh Bomma. Amoxycillin Trihydrate Floating-Bioadhesive Drug Delivery System for Eradication of Helicobacter pylori: Preparation, In Vitro and Ex Vivo Evaluation. J bioequ avail. 2016; 8(3):118-124.
41. Nagaraj B, Anusha K, Narendar D, Sushma P. Formulation and evaluation of microemulsion-based transdermal delivery of duloxetine hydrochloride. International Journal of Pharmaceutical Sciences and Nanotechnology. 2020 Jan 31; 13(1):4773-82.
42. Shruthi K, Narendar D, Arjun N, Kishan V. Development and Antimicrobial Evaluation of Binary Ethosomal Topical Gel of Terbinafine Hydrochloride for the Treatment of Onychomycosis. Int. J. Pharm. Sci. Nanotechnol. 2018; 11:3998-4005.
43. Hu FQ, Jiang SP, Du YZ, et al. Preparation and characterization of stearic acid nanostructured lipid carriers by solvent diffusion method in an aqueous system. Coll Surf B: Biointerf, 2005; 45:167–73.
44. Vamshi KM, Vijay K B, Narendar D. In-situ Intestinal Absorption and Pharmacokinetic Investigations of Carvedilol Loaded Supersaturated Self-Emulsifying Drug System. Pharm Nanotechnol. 2020 May 17. doi: 10.2174/2211738508666200517121637.
45. Pitta S, Dudhipala N, Narala A and Veerabrahma K. Development and evaluation of zolmitriptan transfersomes by Box-Behnken design for improved bioavailability by nasal delivery. Drug Dev Ind Pharm. 2018; 44(3):484-492.
46. Narendar D, Riyaz PMD, Ahmed AY, Nagaraj B. Effect of lipid and edge activator concentration on development of Aceclofenac loaded transfersomes gel for transdermal application: in vitro and ex vivo skin permeation. Dru Dev Ind Pharm. 2020; 46(8):1334-1344.
47. Tirumalesh C, Suram, D.; Dudhipala, N.; Banala, N. Enhanced pharmacokinetic activity of Zotepine via nanostructured lipid carrier system in Wistar rats for oral application. Pharm. Nanotechnol. 2020; 8(2):158-160.
48. Karri V, Butreddy A, Narender R. Fabrication of Efavirenz Freeze Dried Nanocrystals: Formulation, Physicochemical Characterization, In Vitro and Ex Vivo Evaluation. Advanced Science, Engineering and Medicine. 2015; 7(5):385-392.
49. Nagaraj K, D. Narendar and V. Kishan. Development of olmesartan medoxomil optimized nanosuspension using the Box–Behnken design to improve oral bioavailability. Drug Dev Ind Pharm, 2017; 43(7):1186-1196.
50. Butreddy A, Narala A, Dudhipala N. Formulation and characterization of Liquid Crystalline Hydrogel of Agomelatin: In vitro and Ex vivo evaluation. Journal of Applied Pharmaceutical Science. 2015 Sep; 5(09):110-4.
51. Schwarz, C. Solid lipid nanoparticles (SLN) for controlled drug delivery II. Drug incorporation and physicochemical characterization. J Microencapsul. 1999; 16(2):205-213.
52. Jenning V, Gysler A, Schafer-Korting M, et al. Vitamin A-loaded solid lipid nanoparticles for topical use: occlusive properties and drug targeting to the upper skin. Eur J Pharm Biopharm, 2000a ; 49:211–8.
53. Narendar D and Kishan V. Improved anti-hyperlipidemic activity of Rosuvastatin Calcium via lipid nanoparticles: pharmacokinetic and pharmacodynamic evaluation. Euro J Pharm Biopharm. 2017; 110(1):47-57.
54. Arun B, Narendar D and Kishan V. Development of olmesartanmedoxomil lipid based nanoparticles and nanosuspension: Preparation, characterization and comparative pharmacokinetic evaluation. Artificial cells, nanomed and biotech, 2018; 46(1):126-137.
55. Akshaya T, Narendar D, Karthik YJ, Sai PB, Bharathi A, Monica M. Jablonski SM. In Situ Gel of Triamcinolone Acetonide-Loaded Solid Lipid Nanoparticles for Improved Topical Ocular Delivery: Tear Kinetics and Ocular Disposition Studies. Nanomaterials (Basel). 2018 Dec 27; 9(1). pii: E33. doi: 10.3390/nano9010033.
56. Ahmed AAY, Narendar D, Mujumdar S. Ciprofloxacin Loaded Nanostructured Lipid Carriers Incorporated into In-Situ Gels to Improve Management of Bacterial Endophthalmitis. Pharmaceutics, 2020; 12(6):572.
57. Manjunath, K., Venkateswarlu, V. Pharmacokinetics, tissue distribution and bioavailability of clozapine solid lipid nanoparticles after intravenous and intraduodenal administration. J Contr Rel. 2005; 107:215-228.
58. Usha K G, Narendar D and VeerabrahmaKishan. Preparation, characterization and in vivo evaluation of felodipine solid lipid nanoparticles to improve the oral bioavailability. International Journal of Pharmaceutical Sciences and Nanotechnology. 2015; 8 (4):1-8.
59. Wissing SA, Kayser O, Muller RH. Solid lipid nanoparticles for parenteral drug delivery. Adv Drug Deliv Rev, 2004; 56:1257–72.
60. Siekmann B, Westesen K. Submicron-sized parenteral carrier systems based on solid lipids. Pharm Pharmacol Lett, 1992; 1:123–6.
61. Cavalli R, Bargoni A, Podio V, et al. Duodenal administration of solid lipid nanoparticles loaded with different percentages of tobramycin. J Pharm Sci 2003; 92:1085-95.
62. Shahgaldian P, Gualbert J, Aïssa K, Coleman AW. A study of the freeze-drying conditions of calixarene based solid lipid nanoparticles. Eur J Pharm Biopharm. 2003; 55(2):181-4.
63. Quintanar-Guerrero D, Tamayo-Esquivel D, Ganem-Quintanar A, et al. Adaptation and optimization of the emulsifi cation-diffusion technique to prepare lipidic nanospheres. Eur J Pharm Sci, 2005; 26:211–8.
64. Hu FQ, Jiang SP, Du YZ, et al. Preparation and characterization of stearic acid nanostructured lipid carriers by solvent diffusion method in an aqueous system. Coll Surf B: Biointerf, 2005; 45:167–73.
65. Schubert MA, Muller-Goyman CC. Solvent injection as a new approach for manufacturing lipid nanoparticles – evaluation of the method and process parameters. Eur J Pharm Biopharm, 2003; 55:125–31.
66. Morel S, Terreno E, Ugazio E, et al. NMR relaxometric investigations of solid lipid nanoparticles (SLN) containing gadolinium (III) complexes. Eur J Pharm Biopharm, 1998; 45:157–63.
67. Banala, N, Tirumalesh C, Suram, D. Dudhipala, N. Zotepine loaded lipid nanoparticles for oral delivery: preparation, characterization, and in vivo pharmacokinetic studies. Fut J Pharm Sci, 2020; 6(1):37.
68. Banala N, Cernam T, Suram D, Dudhipala N. Design, development and in vivo pharmacokinetic evaluation of zotepine loaded solid lipid nanoparticles for enhanced oral bioavailability. ACTA Pharmaceutica Sciencia.
69. Narendar Dudhipala, Kishan Veerabrahma. Pharmacokinetic and pharmacodynamic studies of nisoldipine loaded solid lipid nanoparticles by central composite design. Drug Dev Ind Pharm. 2015. (doi:10.3109/03639045.2015.1024685).
70. Narendar D, Karthik Yadav J, Thirupathi G. Comparative study of nisoldipine-loaded nanostructured lipid carriers and solid lipid nanoparticles for oral delivery: preparation, characterization, permeation and pharmacokinetic evaluation. Artificial cells, nanomed and biotech. Early online 11 April, 2018, doi.org/10.1080/21691401.2018.1465068.
71. Thirupathi G, Swetha E and Narendar D. Role of isradipine loaded solid lipid nanoparticles in the pharmacodynamic effect of isradipine in rats. Drug res, 2017; 67(03): 163-169.
72. Guguloth S, D. Narender and V. Kishan. Preparation, Characterization and In vivo Evaluation of Rosuvastatin Calcium Loaded Solid Lipid Nanoparticles. International Journal of Pharmaceutical Sciences and Nanotechnology, 2015; 8(1):2779-2785.
73. Narendar D and Karthik yadav J. Lipid nanoparticles of zaleplon for improved oral delivery by Box-Behnken design: Optimization, in vitro and in vivo evaluation. Drug Dev Ind Pharm, 2017; 43(7):1205-1214.
74. Charcosset C, Assma Ahmed El-Harati, Hatem Fessi. A membrane contactor for the preparation of solid lipid nanoparticles. Desalination, 2006; 200:570–571.
75. Zur Muhlen A, Mehnert W. Drug release and release mechanisms of prednisolone loaded solid lipid nanoparticles. Pharmazie, 1998; 53:552–5.
76. Jenning V, M. Scha¨fer-Korting, S. Gohla,Vitamin A-loaded solid lipid nanoparticles for topical use: drug release properties, J. Controlled Rel. 2000a ; 66:115–126.
77. Narendar D, Thirupathi G. Neuroprotective effect of ropinirole loaded lipid nanoparticles hydrogel for Parkinson’s disease: preparation, in vitro, ex vivo, pharmacokinetic and pharmacodynamic evaluation. Pharmaceutics, 2020; 12(5):448.
78. Heiati H., Tawashi R., Phillips N.C. Solid lipid nanoparticles as drug carriers: plasma stability and biodistribution of solid lipid nanoparticles containing the lipophilic prodrug 3'-azido-3'-deoxythymidine palmitate in mice. International Journal of Pharmaceutics, 1998; 174:71–80.
79. Igartua M, Saulnier P, Heurtault B, et al. Development and characterization of solid lipid nanoparticles loaded with magnetite. Int J Pharm, 2002; 233:149–57.
80. Jores K, Mehnert W, Dreschler M, et al. Investigations on the structure of solid lipid nanoparticles (SLN) and oil-loaded solid lipid nanoparticles by photon correlation spectroscopy, fi eld-flow fractionation and transmission electron microscopy. J Control Release, 2004; 95:217–7.
81. Narendar D, Youssef AAA, and Banala N. Colloidal lipid nanodispersion enriched hydrogel of antifungal agent for management of fungal infections: comparative in-vitro, ex-vivo and in-vivo evaluation for oral and topical application. Chemistry and Physics of Lipids 2020); 104981.
82. Liedtke S, Wissing SA, Muller RH, et al. Inflence of high pressure homogenisation equipment on nanodispersions characteristics. Int J Pharm, 2000; 196:183–5.
83. Mühlen, A.Z., Schwarz, C., Mehnert, W. Solid lipid nanoparticles (SLN) for controlled release drug delivery-drug release and release mechanism. Eur J Pharm Biopharm. 1998; 45:149-155.
84. Narendar D, Govardhan K. Capecitabine lipid nanoparticles for anti-colon cancer activity in 1, 2-dimethylhydrazine induced colon cancer: Preparation, cytotoxic, pharmacokinetic and pathological evaluation. Drug dev Ind pharm, Eraly online, March 2018. doi: 10.1080/03639045.2018.1445264.
85. Paliwal R, Rai S, Vaidya B, et al. Effect of lipid core material on characteristics of solid lipid nanoparticles designed for oral lymphatic delivery. Nanomedicine: NBM 2009; 5:184-91.
86. Shahgaldian P, Da Silva E, Coleman AW, et al. Para-acyl-calix-arene based solid lipid nanoparticles (SLNs): a detailed study of preparation and stability parameters. Int J Pharm, 2003; 253:23–38.
87. Narendar D, Youssef AAA, Banala N. Colloidal lipid nanodispersion enriched hydrogel of antifungal agent for management of fungal infections: comparative in-vitro, ex-vivo and in-vivo evaluation for oral and topical application. Chemistry and Physics of Lipids 2020; 104981.
88. Uner M, Wissing SA, Yener G, et al. Investigation of skin moisturizing effect and skin penetration of ascorbyl palmitate entrapped in solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) incorporated into hydrogel. Pharmazie, 2005b; 60:751–5.
89. Venkateswarlu V, Manjunath K. Preparation, characterization and in vitro release kinetics of clozapine solid lipid nanoparticles. J Control Release, 2004; 95:627–38.
90. Zur Mühlen A, Zur Mühlen E, Niehus H, Mehnert W. Atomic force microscopy studies of solid lipid nanoparticles. Pharmaceutical research. 1996 Sep 1; 13(9):1411-6.
91. Dubes A, Parrot-Lopez H, Abdelwahed W, Degobert G, Fessi H, Shahgaldian P, Coleman AW. Scanning electron microscopy and atomic force microscopy imaging of solid lipid nanoparticles derived from amphiphilic cyclodextrins. European journal of pharmaceutics and biopharmaceutics. 2003 May 1; 55(3):279-82.
92. Chen H, Chang X, Du D, Liu W, Liu J, Weng T, Yang Y, Xu H, Yang X. Podophyllotoxin-loaded solid lipid nanoparticles for epidermal targeting. Journal of controlled release. 2006 Jan 10; 110(2):296-306.
93. Narendar D, Arjun N, Dinesh S, Karthik J. Biopharmaceutical and preclinical studies of efficient oral delivery of zaleplon as semisolid dispersions with self-emulsifying lipid surfactants. Int J Pharm Sci Nanotech. 2016; 9(1):1-8.
94. Shah R, Eldridge D, Palombo E, Harding I. Optimisation and stability assessment of solid lipid nanoparticles using particle size and zeta potential. Journal of Physical Science. 2014 Jan 1; 25(1).
95. Senapati S, Mehraj T, Dudhipala N, Majumdar S. R12. Preparation and characterization of ligand attached new 8-aminoquinoline derivative loaded nanostructured lipid carriers for liver targeting. 2020. Annual Poster Session. 12. https://egrove.olemiss.edu/pharm_annual_posters/12.
96. Freitas C, Müller RH. Effect of light and temperature on zeta potential and physical stability in solid lipid nanoparticle (SLN™) dispersions. International journal of pharmaceutics. 1998 Jun 15; 168(2):221-9.
97. Tabish M, Samir S, , Sushrut M, Narendar D, Babulal T, Soumyajit M, "R21. Preparation, characterization and stability evaluation of ligand anchored primaquine loaded nanostructured lipid carrier systems for liver targeting" (2020). Annual Poster Session. 21. https://egrove.olemiss.edu/pharm_annual_posters/21.
98. Rohit B, Pal KI. A method to prepare solid lipid nanoparticles with improved entrapment efficiency of hydrophilic drugs. Current Nanoscience. 2013 Apr 1; 9(2):211-20.
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. that allows others to share the work with an acknowledgment of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).