Application of Design Of Expert for the Development and Systematic Optimisation of L-Asparaginase loaded Nanoparticulate Carrier Drug Delivery Systems

  • Gazal Sharma IKGPTU
  • Amit Kumar Goyal Scientist E, National Animal Biotechnology Institute, Hyderabad
  • Anirudh Pratap Singh IKG Punjab Technical University Kapurthala


L-Asparaginase (L-ASN) is a clinically approved chemotherapeutic agent for the treatment of acute lymphoblastic leukaemia and lymphosarcoma. The aim of this research study was to develop and to optimize solid lipid nanoparticle formulation loaded with enzyme L-Asparaginase using response surface methodology (RSM) [1]. The formulation was prepared by a modified double emulsion method followed by solvent evaporation technique using a combination of high-speed homogeniser (10000 rpm) and an automatic hotplate for a temperature 40°C.  Box-Behnken Design (BBD) was involved in the study to establish and to understand the relationship between selected design factors and the experimental data thus obtained. A set of 29 formulations were prepared in triplicate based on the recommendations of BBD.[2] The desired results obtained were found to be in close agreement with the experimental results. The responses were fitted to a quadratic; polynomial model. The statistical validation using Analysis of Variance (ANOVA) was done for the respective fitted models.[3] Response Surface Graphs and 3D contour plots were constructed to understand the effect of independent variables in different combinations on the desired responses. SLN prepared were found to be spherical in shape and the mean particle size ˂198 nm.[4] The polydispersity index (PDI) and the zeta potential recorded for the prepared formulation corresponding to the particle size was 0.096 ± 0.043 and −10.39 mV respectively. The enzyme drug loading was 10.11% ± 2.02 and the enzyme entrapment efficiency was found to be 76.19% ± 1.23. BBD found to be very effective in considering the effects of independent formulation variables to develop an optimised enzyme loaded SLN formulation with sufficient activity of the L-ASN enzyme.

Keywords: Solid Lipid Nanoparticle, Response Surface Methodology, Box-Behnken Design


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Author Biographies

Amit Kumar Goyal, Scientist E, National Animal Biotechnology Institute, Hyderabad

Scientist E, National Animal Institute of Biotechnology, Hyderabad, India

Anirudh Pratap Singh, IKG Punjab Technical University Kapurthala

Dean, IKG Punjab Technical University, Kapurthala, Punjab India 146001


1. Panchagnula R. Transdermal delivery of drugs. Indian J Pharmacol. 1997; 29:140–56.
2. Rao PR, Diwan PV. Permeability studies of cellulose acetate free films for transdermal use: Influence of plasticizers. Pharm Acta Helv. 1997; 72:47–51.
3. Drug Delivery Systems: Getting Drugs to Their Targets in a Controlled Manner; NIH Turning Discovery in Health; 2016
4. De Jong W, Borm P. Drug delivery and nanoparticles: applications and hazards. Int J Nanomedicine. 2008; 3(2):133–149.
5. Huang Z, Hua S, Yang Y, Fang J. Development and evaluation of lipid nanoparticles for camptothecin delivery: a comparison of solid lipid nanoparticles, nanostructured lipid carriers, and lipid emulsion. Acta Pharmacologica Sinica. 2008; 29(9):1094–1102.
6. Üner M, Yener G. Importance of solid lipid nanoparticles (SLN) in various administration routes and future perspectives. Int J Nanomedicine. 2007; 2(3):289–300.
7. Freitas C, Müller R. Correlation between long-term stability of solid lipid nanoparticles (SLN (TM)) and crystallinity of the lipid phase. Eur J Pharm Biopharm. 1999; 47(2):125–132.
8. Rao PR, Diwan PV. Formulation and in vitro evaluation of polymeric films of diltiazem hydrochloride and indomethacin for transdermal administration. Drug Dev Indian Pharm. 1998; 24:327–36
9. Müller R, Rühl D, Runge S, Schulze-Forster K, Mehnert W. Cytotoxicity of solid lipid nanoparticles as a function of the lipid matrix and the surfactant. Pharm Res. 1997; 14(4):458–462.
10. Müller R, Mäder K, Gohla S. Solid lipid nanoparticles (SLN) for controlled drug delivery-a review of the state of the art. European Journal of Pharmaceutics and Biopharmaceutics. 2000; 50(1):161–177.
11. Derakhshandeh K, Erfan M, Dadashzadeh S. Encapsulation of 9-nitrocamptothecin, a novel anticancer drug, in biodegradable nanoparticles: factorial design, characterization and release kinetics. Eur J Pharm Biopharm. 2007; 66(1):34–41.
12. Gohel M, Amin A. Formulation optimization of controlled release diclofenac sodium microspheres using factorial design. J Control Release. 1998; 51(2–3):115–122.
13. Nazzal S, Khan M. Response surface methodology for the optimization of ubiquinone self-nanoemulsified drug delivery system. AAPS PharmSciTech. 2002; 3(1):23–31.
14. Chang J, Huang Y, Hou S, Wang R, Wu P, Tsai Y. Formulation optimization of meloxicam sodium gel using response surface methodology. Int J Pharm. 2007; 338(1–2):48–54.
15. Liu C, Wu C, Fang J. Characterization and formulation optimization of solid lipid nanoparticles in vitamin K1 delivery. Drug Dev Ind Pharm. 2010; 36(7):751–761.
16. Manjunath K, Reddy J, Venkateswarlu V. Solid lipid nanoparticles as drug delivery systems. Methods Find Exp Clin Pharmacol. 2005; 27(2):127–144.
17. Arai H, Suzuki T, Kaseda C, Takayama K. Effect of an Experimental Design for Evaluating the Nonlinear Optimal Formulation of Theophylline Tablets Using a Bootstrap Resampling Technique. Chem Pharm Bull. 2009; 57(6):572–579.
18. El-Malah Y, Nazzal S, Khanfar N. D-optimal mixture design: optimization of ternary matrix blends for controlled zero-order drug release from oral dosage forms. Drug Dev Ind Pharm. 2006; 32(10):1207–1218.
19. Bozkir A, Saka O. Formulation and investigation of 5-FU nanoparticles with factorial design-based studies. Il Farmaco. 2005; 60(10):840–846.
20. Bhavsar M, Tiwari S, Amiji M. Formulation optimization for the nanoparticles-in-microsphere hybrid oral delivery system using factorial design. J Control Release. 2006; 110(2):422–430.
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How to Cite
Sharma, G., Goyal, A., & Singh, A. P. (2019). Application of Design Of Expert for the Development and Systematic Optimisation of L-Asparaginase loaded Nanoparticulate Carrier Drug Delivery Systems. Journal of Drug Delivery and Therapeutics, 9(3-s), 303-308.