Synthesis and characterization of curcumin nanoparticles with and without novel polymer caging

Dr Neelakantan, Prasanna   (Principal Investigator (PI))

Dr Wang Yufeng   (Co-Investigator)

Professor Matinlinna Jukka Pekka   (Co-Investigator)

Professor Cheung Gary Shun Pan   (Co-Investigator)

14

2017-04-15

2018-06-14

150000

Synthesis and characterization of curcumin nanoparticles with and without novel polymer caging

Curcumin, Green synthesis, Nanotechnology

Endocrinology,Biomaterials

201702159011

Seed Fund for Basic Research for New Staff

2016

Completed

KEY ISSUES AND PROBLEMS BEING ADDRESSED 1. Microbiota in root canal systems are organised as complex masses termed biofilms, and complexity of the root canal system exemplifies the challenge in achieving optimal disinfection Bacteria in biofilms show multiple fold resistance to disinfecting agents (Kishen and Haapasalo 2012) due to two main reasons: (i) the biofilm is encapsulated in an extracellular polysaccharide matrix which serves as a protective layer for the biofilms (ii) the biofilms are almost always composed of more than one species of bacteria (Chavez de Paz 2012). The root canal system consists of multiple eccentricities (Moorer and Wesselink 1982) which results in insufficient penetration of irrigating solutions into these spaces. To overcome this problem, irrigant activation techniques such as passive ultrasonic irrigation and sonic activation are used (Susin et al. 2010). The reports on such activation techniques are contradictory. Further, activation of sodium hypochlorite results in rapid inactivation of the solution by degassing and frequent replenishment is necessary (Neelakantan et al. 2015). 2. Conventional irrigation protocols are proteolytic and demineralising in nature, resulting in weakening of radicular dentin; Fracture toughness of root canal treated tis significantly reduced by the irrigating protocols and bacterial enzymes. The conventional irrigation protocol in endodontics involves the use of a proteolytic agent such as sodium hypochlorite to dissolve pulp tissue and disrupt the microbial biofilms, followed by a decalcifying agent such as ethylene diamine tetraacetic acid to remove the inorganic component of the smear layer (Neelakantan et al. 2015). This protocol is erosive to the dentin as it is collagenolytic and demineralising resulting in significant weakening of the root dentin (Ferrari et al. 2004, Neelakantan et al. 2016). The presence of host derived enzymes (matrix metalloproteinases) such as collagenase may increase the magnitude of this problem (Shrestha et al. 2012). 3. Hydrophobicity of curcumin The hydrophobicity of cur cumin decreases its bioavailability (Flora et al. 2013) within the hydrophilic dentin. It is not known if nanoformulations of curcumin would demonstrate hydrophilicity and thereby offer potential antibiofilm effects and collagen cross-linking. One way to offset such a problem is to cage the curcumin nanoparticles in biopolymeric micelles that have amphiphilic components (Gao et al. 2015). 4. Synthesis of nano-encapsulated formulations of curcumin Curcumin has been shown to bring about antibiofilm activity similar to sodium hypochlorite (Neelakantan et al. 2015). While formulations of nanocurcumin have been evaluated previously (Flora et al.2013), its role in root canal disinfection have not been elucidated thus far. The main advantages of curcumin are that it is antimicrobial, anti inflammatory. Fabrication of nanoparticles by physical and chemical methods have limitations including inability to achieve a mono-dispersed phase of nanoparticles and more importantly, environmental hazards, especially where metallic nanoparticles are concerned (El Khoury et al. 2015). However, the synthesis of nanoparticles of natural products such as curcumin could be considered a ""green synthesis"" approach. PURPOSE The application of nanomaterials has a wide scope in the field of dentistry and one important application in endodontics, is the ability to disrupt biofilms. Such nanoparticles have demonstrated antibacterial activity, dentin matrix cross-linking and tissue regeneration (Shrestha et al. 2014). Nanoparticles may be functionalised or decorated with drugs or photosensitizers to serve as effective agents in photodynamic therapy. Such nanoparticles may also have the potential to serve as an integral component of three dimensional scaffolds to offer temporal release of growth factors in regenerative therapies (Bottino et al. 2013). Such avenues need further research. REFERENCES: 1. Kishen A, Haapasalo M. Biofilm models and methods of biofilm assessment. Endod Topics 2010;22:58–78. 2. Chavez de Paz LE. Development of a multispecies biofilm community by four root canal bacteria. J Endod 2012;38:318–23. 3. Moorer WR et al. Factors promoting the tissue dissolving capability of sodium hypochlorite. Int Endod J 1982;15:187–96. 4. Susin L et al. Canal and isthmus debridement efficacies of two irrigant agitation techniques in a closed system. Int Endod J 2010;43:1077–90. 5. Neelakantan P et al. Antibiofilm activity of three irrigation protocols activated by ultrasonic, diode laser or Er:YAG laser in vitro. Int Endod J2015;48:602-10 6. Ferrari M et al. Collagen degradation in endodontically treated teeth after clinical function. J Dent Res 2004;83:414-9. 7. Neelakantan P et al. Influence of irrigation sequence on the adhesion of root canal sealers to dentin: A Fourier transform infrared spectroscopy and push-out bond strength analysis. J Endod 2015.;41:1108-1101. 8. Shrestha A et al.. Characterization of a conjugate between Rose Bengal and chitosan for targeted antibiofilm and tissue stabilization effects as a potential treatment of infected dentin. Antimicrobial Agents Chemother 2012;56:4876-84. 9. Neelakantan P et al. Photoactivation of curcumin and sodium hypochlorite to enhance antibiofilm efficacy in root canal dentin. Photodiag Photodyn Therapy 2015;12:108-114. 10. Flora G et al. Nanocurcumin: a promising therapeutic advancement over ative curcumin. Crit Rev Ther Drug Carr Sys 2013:30:331-68. 11. El Khoury E et al. Green synthesis of curcumin conjugated nanosilver for the applications in nucleic acid sensing and anti-bacterial activity. Colloids and Surfaces B Biointerfaces 2015; 127:274-280 12. Gao M et al.. Covalent and non-covalent curcumin loading in acid-responsive polymeric micellar nanocarriers. Nanotechnology 2015;26: 275101. 13. Shrestha A et al. Photoactivated rose bengal functionalized chitosan nanoparticles produce antibacterial/biofilm activity and stabilize dentin-collagen. Nanomedicine: Nanotechnology, Biology, and Medicine 2014:10:491-501. 14. Bottino MC et al. Bioactive nanofibrous scaffolds for regenerative endodontics. J Dent Res 2013;92:963-969.