Formulation design and optimization of triclosan loaded nanoparticles for enhanced drug delivery across gingival sulcus by Resolution IV modeling of Design Expert®
Keywords:
Design-Expert®, Resolution IV, design of experiment, periodontal disease, triclosanAbstract
The aim of this study was to design and systematically optimize triclosan loaded nanoparticles (TCS-loaded NPs) formulation for the treatment of periodontal disease. Triclosan (TCS) is a broad spectrum antimicrobial agent that has been used in the treatment of the disease. The free drug has poor aqueous solubility and therefore may encounter permeability problems when applied to the oral cavity. Resolution IV model of Design-Expert® software (version 10) was used for the design of experiment and optimization of TCS-loaded NPs. The nanoparticles (NPs) were prepared using the solvent displacement method. Effect of factors that were investigated include drug-polymer ratio, surfactant concentration, stirring speed, stirring duration, and drug-polymer injection rate. Particle size, zeta potential, polydispersity index (PDI) and entrapment efficiency (EE) were the critical quality attributes selected for the study. Desirability function determined by the software for optimized TCS-loaded NPs was 0.704. The observed particle size, PDI, zeta potential and EE of the optimized TCS-loaded NPs was found to be 135 ± 2.3 nm, 0.1 ± 0.012, -30 ± -4 mV and 75 ± 6%, respectively. It was found that particle size increases by elevating the concentration of polymer and decreases with an increase in surfactant concentration and stirring speed. Zeta potential was found to increase when surfactant concentration was reduced. Both surfactant concentration and drug to polymer ratio were found to negatively affect PDI while % EE was positively influenced by the increase in polymer concentration and decrease in surfactant concentration. The use of Design-Expert® software helped in identifying suitable levels of critical quality parameters for preparing improved NPs formulation for delivery of TCS into the periodontal pocket.References
Sc ar z JB, O’C nn r RE, Sc naar RL. Optimization techniques in pharmaceutical formulation processing. In: Banker GS, Rhodes CT, editors. Modern Pharmaceutics. New York: Marcel Dekker, Inc.; 2002. p.1–20.
Avasatthi V, Pawar H, Dora CP, Bansod P, Gill MS, Suresh S. A novel nanogel formulation of methotrexate for topical treatment of psoriasis: optimization, in vitro and in vivo evaluation. Pharm Dev Technol. 2015; 29:1–9.
Singare DS, Marella S, Gowthamrajan K, Kulkarni GT, Vooturi R, Rao PS. Optimization of formulation and process variable of nanosuspension: An industrial perspective. Int J Pharm. 2010; 402(1–2):213–20.
Suyanto A, Noor E, Fahma F, Rusli MS, Djatna T. Development of method of optimized flavor production systems design based on nano-emulsification Kawista (Feronia limonia) Fruit extraction. IOP Conf Ser Earth Environ Sci. 2018; 102(1):1–12.
Patil A, Lakhani P, Taskar P, Wu K-W, Sweeney C, Avula B, et al. Formulation Development, Optimization, and In Vitro – In Vivo Characterization of Natamycin-Loaded PEGylated Nano-Lipid Carriers for Ocular Applications. J Pharm Sci. 2018. Doi: 10.1016/j.xphs.2018.04.014
Gupta S, Kesarla R, Chotai N, Misra A, Omri A. Systematic Approach for the Formulation and Optimization of Solid Lipid Nanoparticles of Efavirenz by High Pressure Homogenization Using Design of Experiments for Brain Targeting and Enhanced Bioavailability. Biomed Res Int. 2017; 2017:1–18.
Kamran M, Ahad A, Aqil M, Imam SS, Sultana Y, Ali A. Design, formulation and optimization of novel soft nano-carriers for transdermal olmesartan medoxomil delivery: In vitro characterization and in vivo pharmacokinetic assessment. Int J Pharm. 2016; 505(1–2):147–58.
Kumar S, Ali J, Baboota S. Design Expert® supported optimization and predictive analysis of selegiline nanoemulsion via the olfactory region with enhanced b av ural p r rmanc n Park ns n’s d s as . Nanotechnology. 2016; 27(43):1–24.
Singh S, Verma D, Mirza MA, Das AK, Dudeja M, Anwer MK, et al. Development and optimization of ketoconazole loaded nano-transfersomal gel for vaginal delivery using Box-Behnken design: In vitro, ex vivo characterization and antimicrobial evaluation. J Drug Deliv Sci Technol. 2017; 39:95–103.
Elkomy MH, Elmenshawe SF, Eid HM, Ali AMA. Topical ketoprofen nanogel: artificial neural network optimization, clustered bootstrap validation, and in vivo activity evaluation based on longitudinal dose response modeling. Drug Deliv. 2016; 23(9):3294–306.
Sabbagh F, Muhamad II, Nazari Z, Mobini P, Taraghdari SB. From formulation of acrylamide-based hydrogels to their optimization for drug release using response surface methodology. Mater Sci Eng C. 2018; 92:20–5.
Ali H, Singh SK. Preparation and characterization of solid lipid nanoparticles of furosemide using quality by design. Part Sci Technol. 2018; 36(6):695–709.
Sukhbir S, Yashpal S, Sandeep A. Development and statistical optimization of nefopam hydrochloride loaded nanospheres for neuropathic pain using Box-Behnken design. Saudi Pharm J. 2016; 24(5):588–99.
Tanner ACR. Anaerobic culture to detect periodontal and caries pathogens. J Oral Biosci. 2015; 57(1):18–26.
Aminu N, Toh S. Applicability of Nanoparticles-Hydrogel Composite in Treating Periodontal Diseases and Beyond. Asian J Pharm Clin Res. 2017; 10(2):65–70.
Aminu N, Chan S, Toh S. Roles of Nanotechnological Approaches in Periodontal Disease Therapy. J Appl Pharm Sci. 2017; 7(7):234–42.
The Royal Veterinary College London. Gingival Sulcus [Internet]. 2002 [cited 2018 Jan 23]. Available from: https://www.rvc.ac.uk/review/dentistry/basics/gingival_landmarks/sulcus.html
Aminu N, Baboota S, Pramod K, Singh M, Dang S, Ansari SH, Sahni, JK, Ali, J. Development and evaluation of triclosan loaded poly-ε-caprolactone nanoparticulate system for the treatment of periodontal infections. J Nanoparticle Res. 2013; 15(11):2075.
Jain N, Jain GK, Javed S, Iqbal Z, Talegaonkar S, Ahmad FJ, et al. Recent approaches for the treatment of periodontitis. Drug Discov Today. 2008; 13(21–22):932–43.
Schwach-Abdellaoui K, Vivien-Castioni N, Gurny R. Local delivery of antimicrobial agents for the treatment of periodontal diseases. Eur J Pharm Biopharm. 2000; 50(2000):83–99.
Pramod K, Aminu N, Ali J. Targeted Drug Delivery Systems for the Treatment of Periodontal Infections. In: Singh B, Katare OP, Govil JN, editors. Biotechnology Volume 8: Novel Drug Delivery. U.S.A.: Studium Press LLC; 2014. p. 97–128.
Kumari N, Pathak K. Dual controlled release, in situ gelling periodontal sol of metronidazole benzoate and serratiopeptidase: statistical optimization and mechanistic evaluation. Curr Drug Deliv. 2012; 9(1):74–84.
Srivastava M, Kohli K, Ali M. Formulation development of novel in situ nanoemulgel (NEG) of ketoprofen for the treatment of periodontitis. Drug Deliv. 2016; 23(1):154–66.
Rosling B, Dahlén G, Volpe A, Furuichi Y, Ramberg P, Lindhe J. Effect of triclosan on the subgingival microbiota of periodontitis-susceptible subjects. J Clin Periodontol. 1997; 24(12):881–887.
Murthy R. Biodegradable polymers. In: Jain N, editor. Controlled and novel drug delivery. New Delhi: CBS
Publisher; 1997. p. 27–51.
Sinha VR, Bansal K, Kaushik R, Kumria R, Trehan A. Poly-epsilon-caprolactone microspheres and nanospheres: an overview. Int J Pharm. 2004; 278(1):1–23.
Aminu N, Chan S-Y, Khan NH, Toh S-M. Concurrent determination of triclosan and flurbiprofen by high-performance liquid chromatography in simulated saliva and its application in dental nanogel formulation. Acta Chromatogr. 2017. 1–6. Doi: 10.1556/1326.2017.00286
Aminu N, Chan S-Y, Khan NH, Farhan AB, Umar MN, Toh S-M. A simple stability-indicating HPLC method for simultaneous analysis of paracetamol and caffeine and its application to determinations in fixed-dose combination tablet dosage form. Acta Chromatogr. 2018; 1–7. Doi: 10.1556/1326.2018.00354
Aminu N, Chan S-Y, Toh S-M. Development and Validation of a Stability-indicating HPLC-UV Method for the Simultaneous Determination of Flurbiprofen and Triclosan in Dental Nanogel Formulations. J Phys Sci. 2018; 29(Suppl. 1):1–7.
Tr pl MD, Ra man JF. Op m za n β-carotene loaded solid lipid nanoparticles preparation using a high shear homogenization technique. J Nanoparticle Res. 2009; 11(3):601–14.
Emami J, Boushehri MSS, Varshosaz J. Preparation, characterization and optimization of glipizide controlled release nanoparticles. Res Pharm Sci. 2014; 9(5):301–314.
Hao J, Fang X, Zhou Y, Wang J, Guo F, Li F, et al. Development and optimization of solid lipid nanoparticle formulation for ophthalmic delivery of chloramphenicol using a Box-Behnken design. Int J Nanomedicine. 2011; 6:683–92.
Nobbmann U. Polydispersity – what does it mean for DLS and chromatography? [Internet]. 2014 [cited 2018 Feb 3]. Available from: http://www.materials-talks.com/blog/2014/10/23/polydispersity-what-does-it-mean-for-dls-and-chromatography/
Shah M, Pathak K. Development and statistical optimization of solid lipid nanoparticles of simvastatin by using 2(3) full-factorial design. AAPS PharmSciTech. 2010; 11(2):489–96.
US National Nanotechnology Initiative. What is Nanotechnology? [Internet]. 2017 [cited 2017 Sep 26]. Available from: https://www.nano.gov/nanotech-101/what/definition
Williams III RO, Vaughn JM. Nanoparticle Engineering. In: Swarbrick J, editor. Encyclopedia of Pharmaceutical Technology. Third Edit. New York: Informa Healthcare USA, Inc.; 2007. p. 2384–98.
Wilczewska AZ, Niemirowicz K, Markiewicz KH, Car H. Nanoparticles as drug delivery systems. Pharmacol reports. 2012; 64(5):1020–37.
Vega E, Egea MA, Valls O, Espina M, GarcÃa ML. Flurbiprofen loaded biodegradable nanoparticles for ophtalmic administration. J Pharm Sci. 2006; 95(11):2393–405.
Downloads
Published
Issue
Section
License
JBCS Publication Ethics
JBCS is committed to ensure the publication process follows specific academic ethics. Hence, Authors, Reviewers and Editors are required to conform to standards of ethical guidelines.
Authors
Authors should discuss objectively the significance of research work, technical detail and relevant references to enable others to replicate the experiments. JBCS do not accept fraudulent or inaccurate statements that may constitute towards unethical conduct.
Authors should ensure the originality of their works. In cases where the work and/or words of others have been used, appropriate acknowledgements should be made. JBCS do not accept plagiarism in all forms that constitute towards unethical publishing of an article.
This includes simultaneous submission of the same manuscript to more than one journal. Corresponding author is responsible for the full consensus of all co-authors in approving the final version of the paper and its submission for publication.
Reviewers
Reviewers of JBCS treat manuscripts received for review as confidential documents. Therefore, Reviewers must ensure the confidentiality and should not use privileged information and/or ideas obtained through peer review for personal advantage.
Reviews should be conducted based on academic merit and observations should be formulated clearly with supporting arguments. In cases where selected Reviewer feels unqualified to review a manuscript, Reviewer should notify the editor and excuse himself from the review process in TWO (2) weeks time from the review offer is made.
In any reasonable circumstances, Reviewers should not consider to evaluate manuscripts if they have conflicts of interest (i.e: competitive, collaborative and/or other connections with any of the authors, companies, or institutions affiliated to the papers).
Editors
Editors should evaluate manuscripts exclusively based on their academic merit. JBCS strictly do not allow editors to use unpublished information of authors without the written consent of the author. Editors are required to take appropriate responsive actions if ethical complaints have been presented concerning a submitted manuscript or published paper.
CONFLICT OF INTEREST
Journal of Biomedical and Clinical Sciences requires authors to declare all competing interests in relation to their work. All submitted manuscripts must include a ‘competing interests section at the end of the manuscript listing all competing interests (financial and non-financial). Where authors have no competing interests, the statement should read ,The authors have declared that no competing interests exist. Editors may ask for further information relating to competing interests.
Editors and reviewers are also required to declare any competing interests and will be excluded from the peer review process if a competing interest exists. Competing interests may be financial or non-financial. A competing interest exists when the authors interpretation of data or presentation of information may be influenced by their personal or financial relationship with other people or organizations. Authors should disclose any financial competing interests but also any non-financial competing interests that may cause them embarrassment if they were to become public after the publication of the article.
HUMAN AND ANIMAL RIGHTS
All research must have been carried out within an appropriate ethical framework. If there is suspicion that work has not taken place within an appropriate ethical framework, Editors will follow the Misconduct policy and may reject the manuscript, and/or contact the author(s) institution or ethics committee. On rare occasions, if the Editor has serious concerns about the ethics of a study, the manuscript may be rejected on ethical grounds, even if approval from an ethics committee has been obtained.
Research involving human subjects, human material, or human data, must have been performed in accordance with the Declaration of Helsinki and must have been approved by an appropriate ethics committee. A statement detailing this, including the name of the ethics committee and the reference number where appropriate, must appear in all manuscripts reporting such research. Further information and documentation to support this should be made available to Editors on request.
Experimental research on vertebrates or any regulated invertebrates must comply with institutional, national, or international guidelines, and where available should have been approved by an appropriate ethics committee. The Basel Declaration outlines fundamental principles to adhere to when conducting research in animals and the International Council for Laboratory Animal Science (ICLAS) has also published ethical guidelines.
A statement detailing compliance with relevant guidelines (e.g. the revised Animals (Scientific Procedures) Act 1986 in the UK and Directive 2010/63/EU in Europe) and/or ethical approval (including the name of the ethics committee and the reference number where appropriate) must be included in the manuscript. The Editor will take account of animal welfare issues and reserves the right to reject a manuscript, especially if the research involves protocols that are inconsistent with commonly accepted norms of animal research. In rare cases, Editors may contact the ethics committee for further information.
INFORMED CONSENT
For all research involving human subjects, informed consent to participate in the study should be obtained from participants (or their parent or guardian in the case of children under 16) and a statement to this effect should appear in the manuscript, this includes to all manuscripts that include details, images, or videos relating to individual participants.
DATA SHARING POLICY
JBCS strongly encourages that all datasets on which the conclusions of the paper rely should be available to readers. We encourage authors to ensure that their datasets are either deposited in publicly available repositories (where available and appropriate) or presented in the main manuscript or additional supporting files, in machine-readable format (such as spreadsheets rather than PDFs) whenever possible
Authors who do not wish to share their data must state that data will not be shared, and give the reason.
COPYRIGHT NOTICE
The JBCS retains the copyright of published manuscripts under the terms of the Copyright Transfer Agreement. However, the journal permits unrestricted use, distribution, and reproduction in any medium, provided permission to reuse, distribute and reproduce is obtained from the Journal's Editor and the original work is properly cited.
While the advice and information in this journal are believed to be true and accurate on the date of its going to press, neither the authors, the editors, nor the publisher can accept any legal responsibility for any errors or omissions that may be made. The publisher makes no warranty, express or implied, with respect to the material contained herein.
Copyright (c) 2023 Journal of Biomedical and Clinical Sciences (JBCS)
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
