FORMULATION, DEVELOPMENT AND CHARACTERIZATION OF DRUG DELIVERY SYSTEMS BASED TELMISARTAN ENCAPSULATED IN SILK FIBROIN NANOSPHERE’S
Objective: The aim of the present work was to formulate silk fibroin (SF) nanospheres (NS’s) for drug delivery application. The current study was designed to advance the water solubility and bio-availability of telmisartan by nanoprecipitation method.
Methods: SF NS’s loaded with TS were prepared by nanoprecipitation method. The drug was dissolved in aqueous solution of SF by using acetone as a non-solvent. The prepared NS’s were then characterized by FTIR, X-ray diffraction and zeta potential, and were evaluated for its, surface morphology, %drug content, encapsulation efficiency and in vitro drug release.
Results: The evaluation results of SF NS’s loaded of TS showed 74.22±0.17 % entrapment efficiency, 35.21±0.02 % of drug loading, and-4.9 mV to-13.6 mV of zeta potential due to the proper bounding of TS with the β-sheets of SF, the particle size reported was within the size range of 160-186 nm having smooth surface and were spherical in shape. The SFNS’s pattern switched from random coil to β-sheet formation on treating with acetone. FTIR and DSC studies marked no such inter-molecular interactions between SF and drug molecules. The % cumulative in vitro drug release from SF NS’s exhibited quick burst release. The in vitro cumulative drug release of SF NS’s of TS it was found that about 74% of the drug was released within 8 h and about 96% of drug released at 24 hr. The rate of drug release increased with the increase in SF ratio.
Conclusion: It is believed that these SF NS’s will find potential applications in drug delivery release as drug carriers, especially poor water-soluble drugs. All these results proposed that SF NS’s are eventuality handy in various drug delivery systems.
2. Wenk E, Merkle HP, Meinel L. Silk fibroin as a vehicle for drug delivery applications. J Controlled Release 2011;150:128–41.
3. Shi PJ, Goh JCH. Self-assembled silk fibroin particles: tunable size and appearance. Powder Technol 2012;215:85–90.
4. Wang XQ, Yucel T, Lu Q, Hu X, Kaplan DL. Silk nanospheres and microspheres from silk/PVA blend films for drug delivery. Biomaterials 2010;31:1025–35.
5. Li X, Qin J, Ma J. Silk fibroin/poly (vinyl alcohol) blend scaffolds for controlled delivery of curcumin. Regener Biomater 2015;2:97–105.
6. Zhang YQ, Shen WD, Xiang RL, Wang W. Formation of silk fibroin nanoparticles in a water-miscible organic solvent and their characterization. J Nanopart Res 2007;9:885–900.
7. Cao Y, Liu F, Chen Y, Yu T, Lou D, Guo Y, et al. Drug release from core-shell PVA/silk fibroin nanoparticles fabricated by one-step electrospraying. Sci Reports 2017;11913:1-9.
8. Dickerson BM, Dennis BP, Tondiglia PV, Nadeau JL, Singh KM, Drummy LF, et al. 3D printing of regenerated silk fibroin and antibody-containing microstructures via multi-photon lithography. ACS Biomaterial Sci Eng 2017;9:2064–75.
9. Shahid Ud Din Wani, Gangadharappa HV. Silk fibroin based drug delivery applications: promises and challenges. Curr Drug Targets 2018;19:1177–90.
10. Yao Y, Wang W, Li M, Ren H, Caiyu C, Jialiang Wang J, et al. Curcumin exerts its antihypertensive effect by downregulating the AT1 receptor in vascular smooth muscle cells. Scientific Reports 2016;6:1-8.
11. Velasquez MT. Angiotensin II receptor blockers. A new class of antihypertensive drugs. Arch Fam Med 1996;5:351-6.
12. Dasgupta C, Zhang L. Angiotensin II receptors and drug discovery in cardiovascular disease. Drug Discovery Today 2011;16:22–34.
13. Sharma M, Sharma R, Jain KD. Nanotechnology-based approaches for enhancing oral bioavailability of poorly water-soluble antihypertensive drugs. Scientifica 2016;8525679:1-11.
14. Patela J, Dhingania A, Garala K. Design and development of solid nanoparticulate dosage forms of telmisartan for bioavailability enhancement by integration of experimental design and principal component analysis. Powder Technol 2014;258:331-43.
15. Park J, Cho W, Cha KH, Ahn J, Han K, Hwang SJ. Solubilization of the poorly water-soluble drug, telmisartan, using supercritical anti-solvent (SAS) process. Int J Pharm 2013;441:50–5.
16. Kim UJ, Park J, Kim HJ, Wada M, Kaplan DL. Three-dimensional aqueous-derived biomaterial scaffolds from silk fibroin. Biomaterial 2005;26:2775-85.
17. Hofmann S, Wong Po Foo CT, Rossetti F. Silk fibroin as an organic polymer for controlled drug delivery. J Controlled Release 2006;111:219–27.
18. Jin HJ, Park J, Karageorgiou V, Kim JU, Valluzzi R, Cebe P, et al. Water-stable silk films with reduced ?-sheet content. Adv Funct Mater 2005;15:1241-7.
19. Simchua W, Narkkong NA, Baimark Y. Silk fibroin nanospheres for controlled gentamicin sulfate delivery. Res J Nanosci Nanotech 2011;1:34-41.
20. Meinel L, Hofmann S, Karageorgiou VC, Kirker Head C, McCool J, Gronowicz G, et al. The inflammatory responses to silk films in vitro and in vivo. Biomaterials 2005;26:147–55.
21. Rockwood DN, Preda RC, Yücel T, Wang X, Lovett ML. Materials fabrication from bombyx mori silk fibroin. Nat Protoc 2011;6:1612-31.
22. Chen M, Shao Z, Chen X. Paclitaxel-loaded silk fibroin nanospheres. J Biomed Mater Res Part A 2012;100A:203–10.
23. Kundu J, Chung Y II, Kim HY. Silk fibroin nanoparticles for cellular uptake and control release. Int J Pharm 2010; 388:242-50.
24. Ling SJ, Qi ZM, Knight DP, Shao Z, Chen X. Synchrotron FTIR microspectroscopy of single natural silk fibers. Biomacromolecule 2011;12:3344–9.
25. Wu M, Yang W, Chen S. Size-controllable dual drug-loaded silk fibroin nanospheres through a facile formation process. J Mater Chem B 2018;6:1179-86.
26. Costa P, Sousa LJM. Modeling and comparison of dissolution profiles. Eur J Pharm Sci 2001;13:123-33.
27. Baimark Y, Srisuwan Y. Silk fibroin spheres crosslinked by polyethylene glycol diglycidyl ether for drug delivery. Int J Chem Appl 2012;4:259-69.
28. Higuchi T. Mechanism of sustained-action medication theoretical analysis of the rate of release of solid drugs dispersed in solid matrices. J Pharm Sci 1963;52:1145-9.
29. Korsmeyer WR, Gumy R, Doelker E, Buri P, Nikolaos A Peppas. Mechanisms of solute release from porous hydrophilic polymers. Int J Pharm 1983;15:25-35.
30. Jin HJ, Park J, Karageorgiou V, Kim UJ, Valluzzi R, Cebe P, et al. Water-stable silk films with reduced ?-sheet content. Adv Funct Mater 2005;15:1241–7.
31. Tanaka T, Tanigami T, Yamaura K. Phase separation structure in poly (vinyl alcohol)/silk fibroin blend films. Polym Int 1998;45:175–84.
32. Numata K, Subramanian B, Currie HA, Kaplan DL. Bioengineered silk protein-based gene delivery systems. Biomaterials 2009;30:5775–84.
33. Gupta V, Aseh A, Ríos CN, Aggarwal BB, Mathur AB. Fabrication and characterization of silk fibroin-derived curcumin nanoparticles for cancer therapy. Int J Nanomed 2009;4:115–22.
34. Yu Qing Z, Ru Li X, Hai Bo Y, Xiao Xiao C. Preparation of silk fibroin nanoparticles and their application to immobilization of L-asparaginase. Chem J Chin Univ 2008;29:628–33.
35. Sahoo SK, Suresh P, Acharya U. Design and development of self-microemulsifying drug delivery systems (SMEDDS) of telmisartan for enhancement of in vitro dissolution and oral bioavailability in rabbit. Int J Appl Pharm 2018;10:117-26.
36. Hiendrawan S, Hartanti AW, Veriansyah B, Widjojokusumo E, Tjandrawinata RR. Solubility enhancement of ketoconazole via salt and cocrystal formation. Int J Pharm Pharm Sci 2015;7:160-4.