Abstract
Background: Chitosan, a naturally occurring polymer, has interesting applications in the field of drug delivery due to its plentiful advantages as biodegradability, biocompatibility and nontoxic nature. Nigella sativa essential oil is unstable, volatile, and insoluble in water and these problems confine its usage in developing new medicines.
Objective: This study focuses on developing a chitosan-based nanocarrier for the encapsulation of Nigella Sativa essential oil. By using Quality by design outline, the quality target product outline, critical quality attributes and critical material attributes were defined by knowledge and risk-based procedures. Methods: According to defined critical material attributes, Optimization software (Statgraphics XVII) was used to study the effect of the processing parameters. The processing parameters identified and fixed first with a “One factor at a time” approach. Various physicochemical characterization techniques were performed. Results: As a result, the ratio of chitosan to benzoic acid (2:1) along with the stirring rate (4000 rpm) produced minimum-sized particles (341 nm) with good stability. The anti-bacterial activity study using Staph. Aureus strain proved that the optimized nanoparticles were more efficacious than the pure oil based on the diameter of inhibition zone obtained (diameter =5.5 cm for optimized formula vs diameter = 3.6 cm for pure oil). Furthermore, MTT (methyl thiazolyl-diphenyl-tetrazolium bromide) assay was performed to compare the in vitro cytotoxicity using two different cell lines (i.e. HCT 116 for colorectal carcinoma and PC3 for prostatic cancer). It was found that in both cell lines, the optimized nanoparticles had noteworthy antiproliferative properties illustrated by determining the concentration at which 50% of growth is inhibited (IC50). The optimized nanoparticles showed lower IC50 (17.95 ±0.82 and 4.02 ±0.12μg/ml) than the bare oil IC50 (43.56 ±1.95 and 29.72 ±1.41μg/ml).Keywords: Nigella sativa, chitosan nanoparticles, optimization, one factor at a time, benzoic acid, biodegradability.
Graphical Abstract
[1]
Mastrobattista E. Advanced drug delivery in motion. Int J Pharm 2013; 454(1): 517-20.
[http://dx.doi.org/10.1016/j.ijpharm.2013.05.002]
[http://dx.doi.org/10.1016/j.ijpharm.2013.05.002]
[2]
Natrajan D, Srinivasan S, Sundar K, Ravindran A. Formulation of essential oil-loaded chitosan–alginate nanocapsules. J Food Drug Anal 2015; 23(3): 560-8.
[http://dx.doi.org/10.1016/j.jfda.2015.01.001]
[http://dx.doi.org/10.1016/j.jfda.2015.01.001]
[3]
Sarmento B, Ribeiro A, Veiga F, Sampaio P, Neufeld R, Ferreira D. Alginate/chitosan nanoparticles are effective for oral insulin delivery. Pharm Res 2007; 24(12): 2198-206.
[http://dx.doi.org/10.1007/s11095-007-9367-4]
[http://dx.doi.org/10.1007/s11095-007-9367-4]
[4]
Li S, Yunna C, Yali Z, et al. Preparation of 5-fluorouracil-loaded chitosan nanoparticles and study of the sustained release in vitro and in vivo. Asian J Pharm Sci 2017; 12: 418-23.
[http://dx.doi.org/10.1016/j.ajps.2017.04.002]
[http://dx.doi.org/10.1016/j.ajps.2017.04.002]
[5]
Saydam M, Takka S. Development and in-vitro evaluation of pH-independent release matrix tablet of weakly acidic drug valsartan using quality by design (QbD) Tools. Drug Dev Ind Pharm 2018; 44(12): 1905-17.
[http://dx.doi.org/10.1080/03639045.2018.1496450]
[http://dx.doi.org/10.1080/03639045.2018.1496450]
[6]
Duschatzky CB, Possetto ML, Talarico LB. Evaluation of chemical and antiviral properties of essential oils from South American plants. Antivir Chem Chemother 2005; 16(4): 247-51.
[http://dx.doi.org/10.1177/095632020501600404]
[http://dx.doi.org/10.1177/095632020501600404]
[7]
Akhtar MS, Degaga B, Azam T. Antimicrobial activity of essential oils extracted from medicinal plants against the pathogenic microorganisms: A review. Issue Biol Sci Pharm Res 2014; 2(1): 1-7.
[8]
Al-Mariri A, Safi M. In vitro antibacterial activity of several plant extracts and oils against some gram-negative bacteria. Iran J Med Sci 2014; 39(1): 36-43. PMCid:PMC3895893
[9]
Mukhtar H, Qureshi AS, Anwar F, Mumtaz MW, Marcu M. Nigella
sativa L. seed and seed oil: Potential sources of highvaluecomponents
for development of functional foods and nutraceuticals/pharmaceutical. J Essent Oil Res 2019; 31(3): 171-
83.
[http://dx.doi.org/10.1080/10412905.2018.1562388]
[http://dx.doi.org/10.1080/10412905.2018.1562388]
[10]
Sari Y, Dhadhang WK, Saryono N, Arington IG. Formulation and
evaluation of nigella Sativa oil gel for accelerating diabetic wound
healing. Asian J pharmabiolo Res 2014; 4: 16-22.
[11]
Ahmad A, Hussain A, Mujeeb M, et al. Review on therapeutic potential of Nigella sativa: A miracle herb. Asian Pac J Trop Biomed 2013; 3: 337-52.
[12]
Koroch AR, Rodolfo JH, Zygadlo JA. Bioactivity of essential oils
and their components. In: berger r.g. (EDS) flavors and fragrances.
Springer, Berlin, Heidelberg, Germany, 2007, pp. 87-115
[http://dx.doi.org/10.1007/978-3-540-49339-6_5]
[http://dx.doi.org/10.1007/978-3-540-49339-6_5]
[13]
Khan MA, Chen HC, Tania M, Zhang DZ. Anti-cancer activities of Nigella sativa (black cumin). Afr J Tradit Complem Alternat Med 2011; 8(5): 226-32.
[http://dx.doi.org/10.4314/ajtcam.v8i5S.10]
[http://dx.doi.org/10.4314/ajtcam.v8i5S.10]
[14]
Nazzaro F, Coppola R, Fratianni F, De Martino L, De Feo D. Effect of essential oils on pathogenic bacteria. Pharmaceuticals 2013; 6(12): 1451-74.
[http://dx.doi.org/10.3390/ph6121451]
[http://dx.doi.org/10.3390/ph6121451]
[15]
Calvo P, Remunan-Lopez C, Vila-Jato JL, Alonso MJ. Chitosan and chitosan/ethylene oxide-propylene oxide block copolymer nanoparticles as novel carriers for proteins and vaccines. Pharm Res 1997; 14(10): 1431-6.
[http://dx.doi.org/10.1023/A:1012128907225]
[http://dx.doi.org/10.1023/A:1012128907225]
[16]
Vila A, Sanchez A, Tobio M, Calvo P, Alonso MJ. Design of biodegradable particles for protein delivery. J Control Release 2002; 78(1-3): 15-24.
[http://dx.doi.org/10.1016/S0168-3659(01)00486-2]
[http://dx.doi.org/10.1016/S0168-3659(01)00486-2]
[17]
Aktas Y, Andrieux K, Alonso MJ, et al. Preparation and in vitro evaluation of chitosan nanoparticles containing a caspase inhibitor. Int J Pharm 2005; 298(2): 378-83.
[http://dx.doi.org/10.1016/j.ijpharm.2005.03.027]
[http://dx.doi.org/10.1016/j.ijpharm.2005.03.027]
[18]
Elnaggar YSR, Etman SM, Abdelmonsif DA, Abdallah OY. Intranasal piperine-loaded chitosan nanoparticles as brain-targeted therapy in alzheimer’s disease: Optimization, biological efficacy and potential toxicity. J Pharm Sci 2015; 104(10): 3544-56.
[http://dx.doi.org/10.1002/jps.24557]
[http://dx.doi.org/10.1002/jps.24557]
[19]
Snehalatha B, Momin M, Mishal AV, Kale TR. Development and
validation of spectrophotometric method for simultaneous estimation
of Nigella sativa seed oil and ginger extract in the same dosage
form. Int J Pharm Sci Res 2014; 5(12): 1000-5. DOI:10.13040/IJPSR.0975-8232.5 (12).1000-05
[20]
Fazil S, Haque S, Kumar M, Baboota S, Sahni JK, Ali J. Development and evaluation of rivastigmine loaded chitosan nanoparticles for brain targeting. Eur J Pharm Sci 2012; 47(1): 6-15.
[http://dx.doi.org/10.1016/j.ejps.2012.04.013]
[http://dx.doi.org/10.1016/j.ejps.2012.04.013]
[21]
Abd-Elbary A, El-laithy HM, Tadros MI. Sucrose stearate-based proniosomes derived niosomes for the nebulisable delivery of cromolyn sodium. Int J Pharm 2008; 357: 189-98.
[http://dx.doi.org/10.1016/j.ijpharm.2008.01.056]
[http://dx.doi.org/10.1016/j.ijpharm.2008.01.056]
[22]
Arafa MG, Ayoub BM. DOE optimization of nano-based carrier of pregabalin as hydrogel: New therapeutic & chemometric approaches for controlled drug delivery systems. Sci Rep 2017; 7: 41503.
[http://dx.doi.org/10.1038/srep41503]
[http://dx.doi.org/10.1038/srep41503]
[23]
Sarath CC, Shirwalkar A, Kiron SS. Development and evaluation of chitosan containing ciprofloxacin β- CD complex. Int J Pharm Tech Res 2010; 2(1): 246-52.
[24]
Natella F, Nardini M, Felice MD, Scaccini C. Benzoic and cinnamic acid derivatives as antioxidants: Structure-activity relation. J Agric Food Chem 1999; 47(4): 1453-9.
[http://dx.doi.org/10.1021/jf980737w]
[http://dx.doi.org/10.1021/jf980737w]
[25]
Ait BE, Eullaffroy P, Clément C, Vernet G. Chitosan improves development, and protects Vitis vinifera L. against Botrytis cinerea. Plant Cell Reports 2004; 22: 608-14.
[http://dx.doi.org/10.1007/s00299-003-0733-3] [PMID: 14595516]
[http://dx.doi.org/10.1007/s00299-003-0733-3] [PMID: 14595516]
[26]
Hussain Z, Sahudin S. Preparation, characterization and colloidal stability of chitosan-tripolyphosphate nanoparticles: Optimization of formulation and process parameters. Int J Pharm Pharm Sci 2016; 8(3): 297-308.
[27]
Gan Q, Wang T, Cochrane C, McCarron P. Modulation of surface charge, particle size and morphological properties of chitosan-TPP nanoparticles intended for gene delivery. Colloids Surf Biointerfaces 2005; 44: 65-73.
[http://dx.doi.org/10.1016/j.colsurfb.2005.06.001]
[http://dx.doi.org/10.1016/j.colsurfb.2005.06.001]
[28]
Hu B, Pan C, Sun Y, et al. Optimization of fabrication parameters to produce chitosan- tripolyphosphate nanoparticles for delivery of tea catechins. J Agric Food Chem 2008; 56: 7451-8.
[http://dx.doi.org/10.1021/jf801111c]
[http://dx.doi.org/10.1021/jf801111c]
[29]
Liu H, Gao C. Preparation and properties of ionically cross-linked chitosan nanoparticles. Polym Adv Technol 2009; 20: 613-9.
[http://dx.doi.org/10.1002/pat.1306]
[http://dx.doi.org/10.1002/pat.1306]
[30]
Fan W, Yan W, Xu Z, Ni H. Formation mechanism of monodisperse, low molecular weight chitosan nanoparticles by ionic gelation technique. Colloids Surf B 2012; 90: 21-7.
[http://dx.doi.org/10.1016/j.colsurfb.2011.09.042]
[http://dx.doi.org/10.1016/j.colsurfb.2011.09.042]
[31]
Qun G, Ajun W. Effects of molecular weight, degree of acetylation and ionic strength on surface tension of chitosan in dilute solution. Carbohydr Polym 2006; 64: 29-36.
[http://dx.doi.org/10.1016/j.carbpol.2005.10.026]
[http://dx.doi.org/10.1016/j.carbpol.2005.10.026]
[32]
Hajdu I, Bodnár M, Filipcsei G, et al. Nanoparticles prepared by self-assembly of chitosan and poly-glutamic acid. Colloid Polym Sci 2008; 286: 343-50.
[http://dx.doi.org/10.1007/s00396-007-1785-7]
[http://dx.doi.org/10.1007/s00396-007-1785-7]
[33]
Beyki M, Zhaveh S, Khalili ST, et al. Encapsulation of menthapiperita essential oils in chitosan- Cinnamic acid nanogel with enhanced antimicrobial activity against Aspergillus flavus. Ind Crops Products 2014; 54: 310-9.
[http://dx.doi.org/10.1016/j.indcrop.2014.01.033]
[http://dx.doi.org/10.1016/j.indcrop.2014.01.033]
[34]
Lapitsky Y. Ionically crosslinked polyelectrolyte nanocarriers: Recent advances and open problems. Curr Opin Colloid Interface Sci 2014; 19: 122-30.
[http://dx.doi.org/10.1016/j.cocis.2014.03.014]
[http://dx.doi.org/10.1016/j.cocis.2014.03.014]
[35]
Paromita I, Jorrit JW, Adam B, Jukka R. Chitosan-based nano-embedded microparticles: Impact of Nanogel composition on physicochemical properties. Pharmaceutics 2017; 9: 1.
[http://dx.doi.org/10.3390/pharmaceutics9010001] [PMID: PMC5374367]
[http://dx.doi.org/10.3390/pharmaceutics9010001] [PMID: PMC5374367]
[36]
Khalili ST, Mohsenifar A, Beyki M, et al. Encapsulation of thyme essential oils in chitosan-benzoic acid nanogel with enhanced antimicrobial activity against Aspergillus flavus. LWT-Food Sci Technol 2015; 60: 502-8.
[http://dx.doi.org/10.1016/j.lwt.2014.07.054]
[http://dx.doi.org/10.1016/j.lwt.2014.07.054]
[37]
Chouhan S, Sharma K, Guleria S. Antimicrobial activity of some essential oils- Present status and future perspectives. Medicines 2017; 4: 58.
[http://dx.doi.org/10.3390/medicines4030058]
[http://dx.doi.org/10.3390/medicines4030058]
[38]
Zhu HJ, Liu XM, Yangn H, Shen XD. Effect of the stirring rate on physical and electrochemical properties of LiMnPO4 nanoplates prepared in a polyol process. Ceram Interfaces 2014; 40: 6699-704.
[http://dx.doi.org/10.1016/j.ceramint.2013.11.131]
[http://dx.doi.org/10.1016/j.ceramint.2013.11.131]
[39]
Papadimitriou S, Bikiaris D, Avgoustakis K, Karavas E, Georgarakis M. Chitosan nanoparticles loaded with dorzolamide and pramipexole. Carbohydr Polym 2008; 73: 44-54.
[http://dx.doi.org/10.1016/j.carbpol.2007.11.007]
[http://dx.doi.org/10.1016/j.carbpol.2007.11.007]
[40]
Zivanovic S, Chi SD. Antimicrobial activity of chitosan films enriched with essential oils. J Food Sci 2005; 70: 45-51.
[http://dx.doi.org/10.1111/j.1365-2621.2005.tb09045.x]
[http://dx.doi.org/10.1111/j.1365-2621.2005.tb09045.x]
[41]
Mulik RS, Monkkonen J, Juvonen RO, Mahadik KR, Paradkar AR. ApoE3 mediated polymeric nanoparticles containing curcumin: Apoptosis induced in vitro anticancer activity against neuroblastoma cells. Int J Pharm 2012; 437: 29-41.
[http://dx.doi.org/10.1016/j.ijpharm.2012.07.062]
[http://dx.doi.org/10.1016/j.ijpharm.2012.07.062]
[42]
Saxena V, Hussain MD. Polymeric mixed micelles for delivery of curcumin to multidrug resistant ovarian cancer. J Biomed Nanotechnol 2013; 9(7): 1146-54.
[http://dx.doi.org/10.1166/jbn.2013.1632]
[http://dx.doi.org/10.1166/jbn.2013.1632]
[43]
Crooks PA, Worthen DR, Ghosheh OA. Use of naturally
occurring Quinones TQ and Di-TQ as anti-neoplastic and cytotoxic
agent. US006218434B1 (1999)
[44]
Mazzi EA, Soliman KF. Nutraceutical composition and method
of use for the treatment of cancer. US201002093889 (2010).
Related Books
Localized Micro/Nanocarriers for Programmed and On-Demand Controlled Drug Release
Mixed Polymeric Micelles for Osteosarcoma Therapy: Development and Characterization
A Comprehensive Text Book on Self-emulsifying Drug Delivery Systems
Nanomaterials: Evolution and Advancement towards Therapeutic Drug Delivery (Part II)
Nanomaterials: Evolution and Advancement Towards Therapeutic Drug Delivery (Part I)
Article Metrics
2