Research Article

Surface-tailored nanomixed micelles containing quercetin–salicylic acid physical complex for enhanced cellular and in vivo activities: a quality by design perspective

***Author for correspondence:

;

E-mail Address: premjeetsandhu27@gmail.com

UGC-Centre of Excellence in Applications of Nanomaterials, Nanoparticles & Nanocomposites, Panjab University, Chandigarh 160014, India

Division of Pharmaceutics, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India

UGC-Centre of Advanced Studies (CAS), Panjab University, Chandigarh 160014, India

Search for more papers by this author

Rajendra Kumar

UGC-Centre of Excellence in Applications of Nanomaterials, Nanoparticles & Nanocomposites, Panjab University, Chandigarh 160014, India

Post Graduate Institute of Medical Research & Education (PGIMER) Hospital, Chandigarh 160015, India

Search for more papers by this author

OP Katare

**Author for correspondence:

E-mail Address: dropkatare@yahoo.com

;

E-mail Address: director_research@pu.ac.in

Division of Pharmaceutics, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India

Research Promotion Cell, Panjab University, Chandigarh 160014, India

Search for more papers by this author

Bhupinder Singh

*Author for correspondence:

E-mail Address: bsbhoop@pu.ac.in

;

E-mail Address: bsbhoop@gmail.com

UGC-Centre of Excellence in Applications of Nanomaterials, Nanoparticles & Nanocomposites, Panjab University, Chandigarh 160014, India

Division of Pharmaceutics, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India

UGC-Centre of Advanced Studies (CAS), Panjab University, Chandigarh 160014, India

Search for more papers by this author

Published Online:19 May 2017https://doi.org/10.2217/nnm-2017-0040

View article

Abstract

Aim: The development of surface-tailored quercetin (QCT)–salicylic acid (SA) physical complex for effective treatment of skin carcinoma. Materials & methods: QCT–SA nanomixed micelles were prepared by the self-assembly method employing the Quality by Design (QbD) approach and evaluated for various in vitro, ex vivo and in vivo parameters. Results: The optimized formulation showed enhanced percent permeation (Q₂₄), in other words, 78.12 ± 0.47, improved in vitro cellular uptake and annexin-V–apoptosis assay exhibited 60.86% cell death. The 7,12-dimethylbenz(a)anthracene and histopathology protocol revealed the improved antineoplastic action of QCT. The dermatokinetic profile showed the maximum drug concentration (6 h), in other words, 416.02 ± 26 μg/cm² in epidermis and 103.65 ± 12 μg/cm² in dermis. Conclusion: The overall performance ratified the safety and efficacy of optimized nanomixed micelless of QCT with SA in a synergistic manner.

Graphical abstract

Keywords:

References

1 Henriksen T, Dahlback A, Larsen SH, Moan J. Ultraviolet-radiation and skin cancer. Effect of an ozone layer depletion. Photochem. Photobiol. 51(5), 579–582 (1990).
Medline CASGoogle Scholar
2 Rice-Evans CA, Miller NJ, Bolwell PG, Bramley PM, Pridham JB. The relative antioxidant activities of plant-derived polyphenolic flavonoids. Free Radic. Res. 22, 375–383 (1995).
Medline CASGoogle Scholar
3 Pdrns. Quercetin. In: Physicians’ Desk Reference for Nutritional Supplements (1st Edition). Physicians’ Desk Reference (PDR). Demoines, Iowa/Medical Economics Data Production Company, NJ, USA (2001).
Google Scholar
4 Ternaux JP, Portalier P. Effect of quercetine on survival and morphological properties of cultured embryonic rat spinal motoneurones. Neurosci. Lett. 332, 33–36 (2002).
Medline CASGoogle Scholar
5 Middleton E, Kandaswami C, Theoharides TC. The effects of plant flavonoids on mammalian cells: implications for inflammation, heart disease, and cancer. Pharmacol. Rev. 52, 673–751 (2000).
Medline CASGoogle Scholar
6 Dok-Go H, Lee KH, Kim HJ et al. Neuroprotective effects of antioxidative flavonoids, quercetin, (+)-dihydroquercetin and quercetin 3-methyl ether, isolated from Opuntia ficus-indica var. saboten. Brain Res. 965, 130–136 (2003).
Medline CASGoogle Scholar
7 Geleijnse JM, Launer LJ, Van Der Kuip DA, Hofman A, Witteman JC. Inverse association of tea and flavonoid intakes with incident myocardial infarction: the Rotterdam study. Am. J. Clin. Nutr. 75, 880–886 (2002).
Medline CASGoogle Scholar
8 Hofmann AF. Clinical implications of physicochemical studies on bile salts. Gastroenterology 48, 484–494 (1965).
Medline CASGoogle Scholar
9 Yu JN, Zhu Y, Wang L et al. Enhancement of oral bioavailability of the poorly water-soluble drug silybin by sodium cholate/phospholipid-mixed micelles. Acta Pharmacol. Sin. 31(6), 759–764 (2010).
Medline CASGoogle Scholar
10 Lane ME. Skin penetration enhancers. Int. J. Pharm. 447(1–2), 12–21 (2013).
Medline CASGoogle Scholar
11 Jin X, Zhang Y, Zhang Z, Che D, Lv H. Juglone loaded poloxamer 188/phospholipid mixed micelles evaluated in vitro and in vivo in breast cancer. Int. J. Pharm. 515(1–2), 359–366 (2016).
Medline CASGoogle Scholar
12 Bhattacharjee J, Verma G, Aswal VK, Date AA, Nagarsenker MS, Hassan PA. Tween 80-sodium deoxycholate mixed micelles: structural characterization and application in doxorubicin delivery. J. Phys. Chem. B 114(49), 16414–16421 (2010).
Medline CASGoogle Scholar
13 Singh B, Kapil R, Nandi M, Ahuja N. Developing oral drug delivery systems using formulation by design: vital precepts, retrospect and prospects. Expert Opin. Drug Deliv. 8(10), 1341–1360 (2011).
Medline CASGoogle Scholar
14 Beg S, Sandhu PS, Batra RS, Khurana RK, Singh B. QbD-based systematic development of novel optimized solid self-nanoemulsifying drug delivery systems (SNEDDS) of lovastatin with enhanced biopharmaceutical performance. Drug Deliv. 22(6), 765–784 (2015).
Medline CASGoogle Scholar
15 Bhatia A, Raza K, Singh B, Katare OP. Phospholipid-based formulation with improved attributes of coal tar. J. Cosmet. Dermatol. 8(4), 282–288 (2009).
MedlineGoogle Scholar
16 Bladon PT, Taylor M, Wood EJ, Cunliffe WJ. Effect of crude coal tar in the mouse-tail model of psoriasis. Arch. Dermatol. Res. 277(2), 121–125 (1985).
Medline CASGoogle Scholar
17 Sandhu PS, Beg S, Mehta F, Singh B, Trivedi P. Novel dietary lipid-based self-nanoemulsifying drug delivery systems of paclitaxel with P-gp inhibitor: implications on cytotoxicity and biopharmaceutical performance. Expert Opin. Drug Deliv. 12(11), 1809–1822 (2015).
MedlineGoogle Scholar
18 Li J, Lin HX, Chen XY et al. Self-assembled structures and excellent surface properties of a novel anionic phosphate diester surfactant derived from natural rosin acids. J. Colloid Interface Sci. 486, 67–74 (2017).
Medline CASGoogle Scholar
19 Patel S, Garapati C, Chowdhury P et al. Development and evaluation of dexamethasone nanomicelles with potential for treating posterior uveitis after topical application. J. Ocul. Pharmacol. Ther. 31(4), 215–227 (2015).
Medline CASGoogle Scholar
20 Langasco R, Spada G, Tanriverdi ST et al. Bio-based topical system for enhanced salicylic acid delivery: preparation and performance of gels. J. Pharm. Pharmacol. 68(8), 999–1009 (2016).
Medline CASGoogle Scholar
21 Fonseca-Santos B, Dos Santos AM, Rodero CF, Gremiao MP, Chorilli M. Design, characterization, and biological evaluation of curcumin-loaded surfactant-based systems for topical drug delivery. Int. J. Nanomedicine 11, 4553–4562 (2016).
Medline CASGoogle Scholar
22 Benaouda F, Jones SA, Martin GP, Brown MB. Localized epidermal drug delivery induced by supramolecular solvent structuring. Mol. Pharm. 13(1), 65–72 (2016).
Medline CASGoogle Scholar
23 Raza K, Singh B, Singla S et al. Nanocolloidal carriers of isotretinoin: antimicrobial activity against Propionibacterium acnes and dermatokinetic modeling. Mol. Pharm. 10(5), 1958–1963 (2013).
Medline CASGoogle Scholar
24 Aggarwal N, Goindi S. Preparation and in vivo evaluation of solid lipid nanoparticles of griseofulvin for dermal use. J. Biomed. Nanotechnol. 9(4), 564–576 (2013).
Medline CASGoogle Scholar
25 Tran NB, Knorr F, Mak WC et al. Gradient-dependent release of the model drug TRITC-dextran from FITC-labeled BSA hydrogel nanocarriers in the hair follicles of porcine ear skin. Eur. J. Pharm. Biopharm. doi:10.1016/j.ejpb.2016.09.016 (2016) (Epub ahead of print).
Google Scholar
26 Garg NK, Tyagi RK, Singh B et al. Nanostructured lipid carrier mediates effective delivery of methotrexate to induce apoptosis of rheumatoid arthritis via NF-kappaB and FOXO1. Int. J. Pharm. 499(1–2), 301–320 (2016).
Medline CASGoogle Scholar
27 Ng SF, Tan LS, Buang F. Transdermal anti-inflammatory activity of bilayer film containing olive compound hydroxytyrosol: physical assessment, in vivo dermal safety and efficacy study in Freund's adjuvant-induced arthritic rat model. Drug Dev. Ind. Pharm. 43(1), 108–119 (2016).
MedlineGoogle Scholar
28 Erdal MS, Ozhan G, Mat MC, Ozsoy Y, Gungor S. Colloidal nanocarriers for the enhanced cutaneous delivery of naftifine: characterization studies and in vitro and in vivo evaluations. Int. J. Nanomedicine 11, 1027–1037 (2016).
Medline CASGoogle Scholar
29 Kheiri Manjili H, Sharafi A, Attari E, Danafar H. Pharmacokinetics and in vitro and in vivo delivery of sulforaphane by PCL–PEG–PCL copolymeric-based micelles. Artif. Cells Nanomed. Biotechnol. doi:10.1080/21691401.2017.1282501 1–12 (2017) (Epub ahead of print).
MedlineGoogle Scholar
30 Winter M, Lodygin D, Verdoodt B, Hermeking H. Deletion of 14–3–3sigma sensitizes mice to DMBA/TPA-induced papillomatosis. Oncotarget 7(30), 46862–46870 (2016).
MedlineGoogle Scholar
31 Sun J, Shen R, Schrock MS et al. Reduction in squamous cell carcinomas in mouse skin by dietary zinc supplementation. Cancer Med. 5(8), 2032–2042 (2016).
Medline CASGoogle Scholar
32 Kuklinski LF, Zens MS, Perry AE, Green AC, Karagas MR. Skin microtopography as a measure of photoaging and risk of squamous cell carcinoma of the skin in a US population. Photodermatol. Photoimmunol. Photomed. 33, 41–48 (2017).
MedlineGoogle Scholar
33 Manjili HK, Sharafi A, Danafar H, Hosseini M, Ramazani A, Ghasemi MH. Poly (caprolactone)–poly (ethylene glycol)–poly (caprolactone)(PCL–PEG–PCL) nanoparticles a valuable and efficient system for in vitro and in vivo delivery of curcumin. RSC Adv. 6(17), 14403–14415 (2016).
CASGoogle Scholar
34 Kheiri Manjili H, Ghasemi P, Malvandi H, Mousavi MS, Attari E, Danafar H. Pharmacokinetics and in vivo delivery of curcumin by copolymeric mPEG–PCL micelles. Eur. J. Pharm. Biopharm. doi:10.1016/j.ejpb.2016.10.003 (2016) (Epub ahead of print).
MedlineGoogle Scholar
35 Sandhu PJ, Rajendra K, Beg S et al. Natural lipids enriched self-nano-emulsifying systems for effective co-delivery of tamoxifen and naringenin: systematic approach for improved breast cancer therapeutics. Nanomed. Nanotechnol. Biol. Med. doi:10.1016/j.nano.2017.03.003 (2017) (Epub ahead of print).
Google Scholar

Vol. 12, No. 11

Metrics

Downloaded 105 times

History

Published online 19 May 2017

Published in print June 2017

Information

Keywords

Financial & competing interests disclosure

The authors are grateful for the financial assistance and grant provided by the UGC-Centre of Excellence in Applications of Nanomaterials, Nanoparticles and Nanocomposites, Panjab University, Chandigarh, India. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

All the experiments were performed as per the protocol approved by Institutional Animal Ethics Committee, Panjab University, Chandigarh (Approval number PU/IAEC/15/166). All animals were kept in the animal house of Panjab University, in polypropylene cages with proper and timely cleaning and at the standard diet.

PDF download