EMULSOMES FOR LIPOPHILIC ANTICANCER DRUG DELIVERY: DEVELOPMENT, OPTIMIZATION AND IN VITRO DRUG RELEASE KINETIC STUDY
Objective: The objective of the present study was to formulate and characterize paclitaxel (Ptx) loaded sterically stabilized emulsomes to provide non-toxic and biocompatible carriers with high Ptx loading efficiency.
Methods: Plain (P-Es) and sterically stabilized emulsomes (SS-Es) were prepared by a modified solvent evaporation method using tristearin as solid lipid and optimized for lipid to (DSPC+CHOL+DSPE-PEG)/ tristearin ratio, lipid/lipid-PEG (DSPC+CHOL/DSPE-PEG) molar ratio, solid lipid concentration, phospholipid concentration, organic to aqueous phase volume and homogenization time based on their effect particle size and entrapment efficiency. Optimized emulsomes were characterized for morphological features, in vitro drug release kinetics and protection from plasma protein.
Results: The emulsomes so formed were uniform in size with a mean particle diameter of 275±5.52 and 195±6.4 nm for P-Es and SS-Es respectively. All the formulations showed pH dependent drug release with a slow and sustained release profile. Slower drug release was observed from sterically stabilized emulsomes than the plain emulsomes. The drug release profile followed the Higuchi model with the Fickian diffusion pattern. The Pegylation of emulsomes significantly reduced the in vitro protein absorption.
Conclusion: The sterically stabilized emulsome can serve as a novel non-toxic platform with longer circulatory time for the delivery of Paclitaxel and other poorly water-soluble drugs as well.
2. Kalepu S, Nekkanti VK. Insoluble drug delivery strategies: review of recent advances and business prospects. Acta Pharm Sinica B 2015;5 Suppl 5:442-53.
3. Tarr BD, Yalkowsky SH. A new parenteral vehicle for the adminstration of some poorly water soluble anti-cancer drugs. JPST 1987;41 Suppl 1:31–3.
4. Patra JK, Das G, Fraceto LF. Nano based drug delivery systems: recent developments and future prospects. J Nanobiotechnol 2018;16:71-80.
5. Elgadir MA, Salama M, Adam A. Antia “breast cancer from various natural sources-review. Int J Pharm Pharm Sci 2015;7(2 Suppl 1):44-7.
6. Iwase K, Oyama Y, Tatsuishi T, Yamaguchi JY, Nishimura Y, Kanada A, et al. Cremophor EL augments the cytotoxicity of hydrogen peroxide in lymphocytes dissociated from rat thymus glands. Toxicol Lett 2004;154:143–8.
7. Gupta R, Gupta M, Mangal S, Agrawal U, Vyas SP. Capsaicin-loaded vesicular systems designed for enhancing localized delivery for psoriasis therapy. Artif Cells Nanomed Biotechnol 2014;44:825-34.
8. Patravale VB, Mirani AG. Preparation and characterization of solid lipid nanoparticles-based gel for topical delivery. Methods in Molecular Biology; 2019. p. 293-302.
9. Sharma A, Mehta V, Parashar A, Patrwal R, Malairaman U. Solid lipid nanoparticle: fabricated through nanoprecipitation and their physicochemical characterization. Int J Pharm Pharm Sci 2016;8 Suppl 10:144-8,
10. Vyas SP, Gupta S. Optimizing efficacy of amphotericin B through nanomodification. Int J Nanomed 2006;1:417-32.
11. Chan JM, Zhang L, Yuet K, Liao G. PLGA–lecithin–PEG core–shell nanoparticles for controlled drug delivery. Biomaterials 2009;30:1627-34.
12. Kumar R. Characterization and biology of nanomaterials for drug delivery. Lipid-based nanoparticles for drug delivery systems: nanoscience and nanotechnology in drug delivery. In: Micro and Nano Technologies. 1st ed. US: Acdemia Press; 2019. p. 47-76.
13. Mainardes RM, Evangelista RC. PLGA nanoparticles containing praziquantel: effect of formulation variables on size distribution. Int J Pharm 2005;290:137–44.
14. Song X, Zhao Y, Wu W, Bi Y, Cai Z, Chen Q, et al. PLGA nanoparticles simultaneously loaded with vincristine sulfate and verapamil hydrochloride: systematic study of particle size and drug entrapment efficiency. Int J Pharm 2008;350(1 Suppl 2):320-9.
15. Hunter RJ. Applications of the zeta potential. In: Zeta Potential in Colloid Science Principles and Applications. 1st ed. US: Acdemia Press; 1981. p. 219-57.
16. Barhoum A, Garcia Betancourt ML, Rahier H, Assche GV. Physicochemical characterization of nanomaterials: polymorph, composition, wettability, and thermal stability. In: Emerging Applications of Nanoparticles and Architecture Nanostructures Current Prospects and Future Trends Micro and Nano Technologies. US: Acdemia Press; 2018. p. 255-78.
17. Chirayil CJ, Abraham J, Mishra RK, George SC, Thomas S. Instrumental techniques for the characterization of nanoparticles. In: Thermal and Rheological Measurement Techniques for Nanomaterials Characterization. Micro and Nano Technologies. 1st ed. Elsevier; 2017. p. 1-36.
18. Venkateswarlu V, Manjunath K. Preparation, characterization and in vitro release kinetics of clozapine solid lipid nanoparticles. J Controlled Release 2004;95:627–38.
19. Jong Suep Baek, Sang Chul Shin, Cheong Weon Cho. Effect of lipid on physicochemical properties of solid lipid nanoparticle of paclitaxel. J Pharm Investig 2012;42:332-42.
20. Prozorov T, Prozorov R, Suslick KS. High velocity interparticle collisions driven by ultrasound. J Am Chem Soc 2004;126 Suppl 43:13890-1.
21. Liu J, Huang Y, Kumar A, Tan A, Jin S, Mozhia A, et al. pH-sensitive nano-systems for drug delivery in cancer therapy. Biotechnol Adv 2014;32:693-710.
22. Kushwaha AK, Vuddanda PR, Karunanidhi P, Singh SK, Singh S. Development and evaluation of solid lipid nanoparticles of raloxifene hydrochloride for enhanced bioavailability. Biomed Res Int 2013;1-9. https://doi.org/10.1155/2013/ 584549.
This work is licensed under a Creative Commons Attribution 4.0 International License.