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Orcinol Glucoside Loaded Polymer - Lipid Hybrid Nanostructured Lipid Carriers: Potential Cytotoxic Agents against Gastric, Colon and Hepatoma Carcinoma Cell Lines

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Abstract

Purpose

Orcinol glucoside (OG) - loaded nanostructured lipid carrier (NLC), coated with polyethylene glycol-25/55-stearate (PEG-25/55-SA), were explored for delivering OG to improve in vitro cytotoxicity against gastrointestinal tract (GIT), colon and hepatoma carcinoma cell lines. It is being expected that the PEGylated formulations would possess the sustainability in withstanding the adverse physiological extremities like the most significant metabolic activities and phase I / II enzymatic activities in the intestines.

Methods

NLCs were prepared using tristearin, oleic acid and PEG-25/55-stearate by hot homogenization-ultrasonic dispersion; characterized by DLS, TEM, SEM, AFM, entrapment efficiency and drug loading capacity studies.

Results

NLC diameter ranged from 160 to 230 nm with negative zeta potential of −8 to −20 mV. TEM/SEM and AFM studies suggest spherical and smooth surface morphologies. Differential scanning calorimetry studies reveal the loss of crystallinity when OG was incorporated into the NLC. NLCs showed initial burst release, followed by sustained release of OG. PEG-NLC exhibited superior anticancer activity against GIT and also in hepatoma cancer cell lines.

Conclusions

This is the first report demonstrating a practical approach for possible oral delivery of OG in GIT and targeting hepatoma cancer, warranting further in vivo studies for superior management of GIT cancer.

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References

  1. Li H, Guissi NEI, Su Z, Ping Q, Sun M. Effects of surface hydrophilic properties of PEG-based mucus-penetrating nanostructured lipid carriers on oral drug delivery. RSC Adv. 2016;6:84164–76.

    Article  CAS  Google Scholar 

  2. Thanki K, Gangwal RP, Sangamwar AT, Jain S. Oral delivery of anticancer drugs: challenges and opportunities. J Control Release. 2013;170:15–40.

    Article  PubMed  CAS  Google Scholar 

  3. Arranja A, Gouveia LF, Gener P, Rafael DF, Pereira C, Schwartz S, et al. Self-assembly PEGylation assists SLN-paclitaxel delivery inducing cancer cell apoptosis upon internalization. Int J Pharm. 2016;501:180–9.

    Article  PubMed  CAS  Google Scholar 

  4. Das S, Chaudhury A. Recent advances in lipid nanoparticle formulations with solid matrix for oral drug delivery. AAPS PharmSciTech. 2011;12:62–76.

    Article  PubMed  CAS  Google Scholar 

  5. Ensign LM, Cone R, Hanes J. Oral drug delivery with polymeric nanoparticles: the gastrointestinal mucus barriers. Adv Drug Deliv Rev. 2012;64:557–70.

    Article  PubMed  CAS  Google Scholar 

  6. Garcia-Fuentes M, Alonso MJ, Torres D. Design and characterization of a new drug nanocarrier made from solid–liquid lipid mixtures. J Colloid Interface Sci. 2005;285:590–8.

    Article  PubMed  CAS  Google Scholar 

  7. Müller RH, MaÈder K, Gohla S. Solid lipid nanoparticles (SLN) for controlled drug delivery–a review of the state of the art. Eur J Pharm Biopharm. 2000;50:161–77.

    Article  PubMed  Google Scholar 

  8. Cho K, Wang X, Nie S, Chen Z, Shin DM. Therapeutic nanoparticles for drug delivery in Cancer. Clin Cancer Res. 2008;14:1310–6.

    Article  PubMed  CAS  Google Scholar 

  9. Singh R, Lillard JW Jr. Nanoparticle-based targeted drug delivery. Exp Mol Pathol. 2009;86:215–23.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  10. Dong Y, Feng S-S. Poly(d,l-lactide-co-glycolide)/montmorillonite nanoparticles for oral delivery of anticancer drugs. Biomaterials. 2005;26:6068–76.

    Article  PubMed  CAS  Google Scholar 

  11. Müller RH, Keck CM. Challenges and solutions for the delivery of biotech drugs – a review of drug nanocrystal technology and lipid nanoparticles. J Biotechnol. 2004;113:151–70.

    Article  PubMed  CAS  Google Scholar 

  12. Wang YY, Lai SK, Suk JS, Pace A, Cone R, Hanes J. Addressing the PEG mucoadhesivity paradox to engineer nanoparticles that “slip” through the human mucus barrier. Angew Chem Int Ed. 2008;47:9726–9.

    Article  CAS  Google Scholar 

  13. Dang H, Meng MHW, Zhao H, Iqbal J, Dai R, Deng Y, et al. Luteolin-loaded solid lipid nanoparticles synthesis, characterization, & improvement of bioavailability, pharmacokinetics in vitro and vivo studies. J Nanopart Res. 2014;16:2347.

    Article  CAS  Google Scholar 

  14. Müller R, Petersen R, Hommoss A, Pardeike J. Nanostructured lipid carriers (NLC) in cosmetic dermal products. Adv Drug Deliv Rev. 2007;59:522–30.

    Article  PubMed  CAS  Google Scholar 

  15. Wong HL, Bendayan R, Rauth AM, Li Y, Wu XY. Chemotherapy with anticancer drugs encapsulated in solid lipid nanoparticles. Adv Drug Deliv Rev. 2007;59:491–504.

    Article  PubMed  CAS  Google Scholar 

  16. Gaur PK, Mishra S, Bajpai M, Mishra A. Enhanced oral bioavailability of efavirenz by solid lipid nanoparticles: in vitro drug release and pharmacokinetics studies. Biomed Res Int. 2014;2014:1–9.

    Article  CAS  Google Scholar 

  17. Müller R, Runge S, Ravelli V, Mehnert W, Thünemann A, Souto E. Oral bioavailability of cyclosporine: solid lipid nanoparticles (SLN®) versus drug nanocrystals. Int J Pharm. 2006;317:82–9.

    Article  PubMed  CAS  Google Scholar 

  18. Nahak P, Karmakar G, Chettri P, Roy B, Guha P, Besra SE, et al. Influence of lipid Core material on physicochemical characteristics of an Ursolic acid-loaded nanostructured lipid carrier: an attempt to enhance anticancer activity. Langmuir. 2016;32:9816–25.

    Article  PubMed  CAS  Google Scholar 

  19. Moghimi SM, Szebeni J. Stealth liposomes and long circulating nanoparticles: critical issues in pharmacokinetics, opsonization and protein-binding properties. Prog Lipid Res. 2003;42:463–78.

    Article  PubMed  CAS  Google Scholar 

  20. Knop K, Hoogenboom R, Fischer D, Schubert US. Poly (ethylene glycol) in drug delivery: pros and cons as well as potential alternatives. Angew Chem Int Ed. 2010;49:6288–308.

    Article  CAS  Google Scholar 

  21. Kouchakzadeh H, Shojaosadati SA, Maghsoudi A, Farahani EV. Optimization of PEGylation conditions for BSA nanoparticles using response surface methodology. AAPS PharmSciTech. 2010;11:1206–11.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Fang Y, Xue J, Gao S, Lu A, Yang D, Jiang H, et al. Cleavable PEGylation: a strategy for overcoming the "PEG dilemma" in efficient drug delivery. Drug Deliv. 2017;24:22–32.

    Article  PubMed  CAS  Google Scholar 

  23. Hama S, Itakura S, Nakai M, Nakayama K, Morimoto S, Suzuki S, et al. Overcoming the polyethylene glycol dilemma via pathological environment-sensitive change of the surface property of nanoparticles for cellular entry. J Control Release. 2015;206:67–74.

    Article  PubMed  CAS  Google Scholar 

  24. Hatakeyama H, Akita H, Harashima H. The Polyethyleneglycol dilemma: advantage and disadvantage of PEGylation of liposomes for systemic genes and nucleic acids delivery to tumors. Biol Pharm Bull. 2013;36:892–9.

    Article  PubMed  CAS  Google Scholar 

  25. Zhang D, Xu H, Hu MN, Deng YH. "PEG dilemma" for liposomes and its solving approaches. Yao Xue Xue Bao. 2015;50:252–60.

    PubMed  CAS  Google Scholar 

  26. Ko JKS, Leung WC, Ho WK, Chiu P. Herbal diterpenoids induce growth arrest and apoptosis in colon cancer cells with increased expression of the nonsteroidal anti-inflammatory drug-activated gene. Eur J Pharmacol. 2007;559:1–13.

    Article  PubMed  CAS  Google Scholar 

  27. Bafna A, Mishra S. Immunostimulatory effect of methanol extract of Curculigo orchioides on immunosuppressed mice. J Ethnopharmacol. 2006;104:1–4.

    Article  PubMed  CAS  Google Scholar 

  28. Wu Q, Fu D-X, Hou A-J, LEI GQ, LIU ZJ, CHEN JK, et al. Antioxidative phenols and phenolic glycosides from Curculigo orchioides. Chem Pharm Bull. 2005;53:1065–7.

    Article  PubMed  CAS  Google Scholar 

  29. Ge J-F, Gao W-C, Cheng W-M, Lu W-L, Tang J, Peng L, et al. Orcinol glucoside produces antidepressant effects by blocking the behavioural and neuronal deficits caused by chronic stress. Eur Neuropsychopharmacol. 2014;24:172–80.

    Article  PubMed  CAS  Google Scholar 

  30. Wu X-Y, Li J-Z, Guo J-Z, Hou B-Y. Ameliorative effects of curculigoside from Curculigo orchioides Gaertn on learning and memory in aged rats. Molecules. 2012;17:10108–18.

    Article  PubMed  CAS  Google Scholar 

  31. Gupta M, Achari B, Pal BC. Glucosides from Curculigo orchioides. Phytochemistry. 2005;66:659–63.

    Article  PubMed  CAS  Google Scholar 

  32. Jain AK, Jain A, Garg NK, Agarwal A, Jain A, Jain SA, et al. Adapalene loaded solid lipid nanoparticles gel: an effective approach for acne treatment. Colloids Surf B. 2014;121:222–9.

    Article  CAS  Google Scholar 

  33. Garcıa-Fuentes M, Torres D, Alonso M. Design of lipid nanoparticles for the oral delivery of hydrophilic macromolecules. Colloids Surf. B. 2003;27:159–68.

    Article  Google Scholar 

  34. Gref R, Lück M, Quellec P, Marchand M, Dellacherie E, Harnisch S, et al. ‘Stealth’corona-core nanoparticles surface modified by polyethylene glycol (PEG): influences of the corona (PEG chain length and surface density) and of the core composition on phagocytic uptake and plasma protein adsorption. Colloids Surf. B. 2000;18:301–13.

    Article  CAS  Google Scholar 

  35. Li X, Lin X, Zheng L, Yu L, Lv F, Zhang Q, et al. Effect of poly (ethylene glycol) stearate on the phase behavior of monocaprate/Tween80/water system and characterization of poly (ethylene glycol) stearate-modified solid lipid nanoparticles. Colloids Surf A Physicochem Eng Asp. 2008;317:352–9.

    Article  CAS  Google Scholar 

  36. Sarmento B, Martins S, Ferreira D, Souto EB. Oral insulin delivery by means of solid lipid nanoparticles. Int J Nanomedicine. 2007;2:743.

    PubMed  PubMed Central  CAS  Google Scholar 

  37. Dadashzadeh S, Derakhshandeh K, Shirazi FH. 9-nitrocamptothecin polymeric nanoparticles: cytotoxicity and pharmacokinetic studies of lactone and total forms of drug in rats. Anti-Cancer Drugs. 2008;19:805–11.

    Article  PubMed  CAS  Google Scholar 

  38. Shah RM, Malherbe F, Eldridge D, Palombo EA, Harding IH. Physicochemical characterization of solid lipid nanoparticles (SLNs) prepared by a novel microemulsion technique. J Colloid Interface Sci. 2014;428:286–94.

    Article  PubMed  CAS  Google Scholar 

  39. Doktorovová S, Araújo J, Garcia ML, Rakovský E, Souto EB. Formulating fluticasone propionate in novel PEG-containing nanostructured lipid carriers (PEG-NLC). Colloids Surf. B. 2010;75:538–42.

    Article  CAS  Google Scholar 

  40. Jia L, Zhang D, Li Z, Duan C, Wang Y, Feng F, et al. Nanostructured lipid carriers for parenteral delivery of silybin: biodistribution and pharmacokinetic studies. Colloids Surf. B. 2010;80:213–8.

    Article  CAS  Google Scholar 

  41. Nahak P, Karmakar G, Roy B, Guha P, Sapkota M, Koirala S, et al. Physicochemical studies on local anaesthetic loaded second generation nanolipid carriers. RSC Adv. 2015;5:26061–70.

    Article  CAS  Google Scholar 

  42. Bunjes H, Koch MH, Westesen K. Effect of particle size on colloidal solid triglycerides. Langmuir. 2000;16:5234–41.

    Article  CAS  Google Scholar 

  43. Bunjes H, Unruh T. Characterization of lipid nanoparticles by differential scanning calorimetry. X-ray and neutron scattering Adv Drug Delivery Rev. 2007;59:379–402.

    Article  CAS  Google Scholar 

  44. Silva A, González-Mira E, García M, Egea M, Fonseca J, Silva R, et al. Preparation, characterization and biocompatibility studies on risperidone-loaded solid lipid nanoparticles (SLN): high pressure homogenization versus ultrasound. Colloids Surf. B. 2011;86:158–65.

    Article  CAS  Google Scholar 

  45. Mukherjee S, Ray S, Thakur R. Solid lipid nanoparticles: a modern formulation approach in drug delivery system. Indian J Pharm Sci. 2009;71:349–58.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  46. Carafa M, Santucci E, Lucania G. Lidocaine-loaded non-ionic surfactant vesicles: characterization and in vitro permeation studies. Int J Pharm. 2002;231:21–32.

    Article  PubMed  CAS  Google Scholar 

  47. Garcia-Fuentes M, Torres D, Alonso MJ. New surface-modified lipid nanoparticles as delivery vehicles for salmon calcitonin. Int J Pharm. 2005;296:122–32.

    Article  PubMed  CAS  Google Scholar 

  48. Wan F, You J, Sun Y, Zhang X-G, Cui F-D, Du Y-Z, et al. Studies on PEG-modified SLNs loading vinorelbine bitartrate (I): preparation and evaluation in vitro. Int J Pharm. 2008;359:104–10.

    Article  PubMed  CAS  Google Scholar 

  49. You J, Wan F, de Cui F, Sun Y, Du Y-Z, Qiang Hu F. Preparation and characteristic of vinorelbine bitartrate-loaded solid lipid nanoparticles. Int. J. Pharm. 2007;343:270–6.

    Article  PubMed  CAS  Google Scholar 

  50. Zhang Y, Huo M, Zhou J, Zou A, Li W, Yao C, et al. DDSolver: an add-in program for modeling and comparison of drug dissolution profiles. AAPS J. 2010;12:263–71.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  51. Chawla JS, Amiji MM. Cellular uptake and concentrations of tamoxifen upon administration in poly (ε-caprolactone) nanoparticles. AAPS J. 2003;5:28–34.

    Article  Google Scholar 

  52. Wong HL, Bendayan R, Rauth AM, Xue HY, Babakhanian K, Wu XY. A mechanistic study of enhanced doxorubicin uptake and retention in multidrug resistant breast cancer cells using a polymer-lipid hybrid nanoparticle system. J Pharmacol Exp Therapeutics. 2006;317:1372–81.

    Article  CAS  Google Scholar 

  53. Wong HL, Rauth AM, Bendayan R, Manias JL, Ramaswamy M, Liu Z, et al. A new polymer–lipid hybrid nanoparticle system increases cytotoxicity of doxorubicin against multidrug-resistant human breast cancer cells. Pharm Res. 2006;23:1574–85.

    Article  PubMed  CAS  Google Scholar 

  54. Zhang H, Li X, Ding J, Xu H, Dai X, Hou Z, et al. Delivery of ursolic acid (UA) in polymeric nanoparticles effectively promotes the apoptosis of gastric cancer cells through enhanced inhibition of cyclooxygenase 2 (COX-2). Int J Pharm. 2013;441:261–8.

    Article  PubMed  CAS  Google Scholar 

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Author notes

  1. Prasant Nahak and Rahul L. Gajbhiye contributed equally to this work.

Authors and Affiliations

  1. Department of Chemistry, University of North Bengal, Darjeeling, West Bengal, 734 013, India

    Prasant Nahak, Gourab Karmakar, Pritam Guha & Biplab Roy

  2. Organic and Medicinal Chemistry Division, CSIR-Indian Institute of Chemical Biology, 4, Raja S. C. Mullcik Road, Jadavpur, Kolkata, West Bengal, 700032, India

    Rahul L. Gajbhiye & Parasuraman Jaisankar

  3. Cancer Biology and Inflammatory Disorder Division, CSIR-Indian Institute of Chemical Biology, 4, Raja S. C. Mullcik Road, Jadavpur, Kolkata, West Bengal, 700032, India

    Shila Elizabeth Besra

  4. Department of Colloid Chemistry, Saint Petersburg State University, Universitetsky pr. 26, Saint Petersburg, 198504, Russia

    Alexey G. Bikov, Alexander V. Akentiev & Boris A. Noskov

  5. Department of Biochemistry, Memorial University of Newfoundland, St. John’s, Newfoundland and Labrador, Canada

    Kaushik Nag

  6. Department of Chemistry and Chemical Technology, Vidyasagar University, Midnapore, West Bengal, 721 102, India

    Amiya Kumar Panda

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  1. Prasant Nahak
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Correspondence to Parasuraman Jaisankar or Amiya Kumar Panda.

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Nahak, P., Gajbhiye, R.L., Karmakar, G. et al. Orcinol Glucoside Loaded Polymer - Lipid Hybrid Nanostructured Lipid Carriers: Potential Cytotoxic Agents against Gastric, Colon and Hepatoma Carcinoma Cell Lines. Pharm Res 35, 198 (2018). https://doi.org/10.1007/s11095-018-2469-3

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  • DOI: https://doi.org/10.1007/s11095-018-2469-3

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