A STRATEGIC PROCESS DEVELOPMENT AND IN VITRO CYTOTOXICITY ANALYSIS OF PACLITAXEL-LOADED LIPOSOMES
DOI:
https://doi.org/10.22159/ijap.2023v15i2.47305Keywords:
Paclitaxel, Liposomes, Cancer, Formulation, EfficacyAbstract
Objective: Liposomes are the controlled-release dosage form that improves the therapeutic efficacy of the drugs, prolongs the duration of action, reduces dosage frequency, and improves patient compliance.
Methods: The thin-film hydration method was used to prepare Paclitaxel liposomes. In this process, cholesterol and sodium deoxycholate were used for the formulation, while chloroform and methanol were used as diluents. Percentage (%) drug release study was carried out in phosphate buffer at pH 7.4 in USP apparatus II (Paddle type)Model no VDA-8D, Veego, Mumbai, India.
Results: Paclitaxel liposomes of various batches showed a percentage yield ranging from 38 to 84%. It was observed that (Encapsulation efficiency)EE% of Batches B1 to B10 were 0,62.33,59.51,50.21,44.30,82.25,88.95,72.34,77.37 and 70.63 percentage, respectively. Data fitting to the Peppas, Higuchi, 1st-order, and zero-order models was used to examine the optimized liposome (B7) release kinetic mechanism. Data comparison was done using the correlation coefficient (R2). Zero-order had an observed correlation coefficient (R2) of 0.9988, which was greater than that for other models. Therefore, it was clear that the medication was released from the formulation after the zero-order release.
Conclusion: The prepared liposomes were subjected to various evaluation parameters like SEM, zeta potential, particle size analysis, drug release study, etc. Data showed that an increased concentration of cholesterol increases the drug release from liposomes. Microscopic images of the B7 batch revealed that liposomes are spherical and have regular surfaces. Formulation B7 shows good results and can be considered an optimized batch that has been selected for further cell line studies. The statistical analysis was used to support the improved formulation.
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References
Ratnaparkhi MP, Gupta J P. Sustained release oral drug delivery system-an overview.
Int J of Pharm Res and Rev.2013; 2(3):11-21.
Bose S, Kaur A, Sharma SK. A review on advances of sustained release drug delivery
system. Int. Res. J. Pharm. 2013;4:1-5.DOI 10.7897/2230-8407.04601
Kumar AR, Aeila AS. Sustained release matrix type drug delivery system: An
overview. World J. Pharm. Pharm. Sci. 2019;9:470-80.
DOI :https://doi.org/10.22270/ajprd.v9i3.954.
Nicolas P, Tod M, Padoin C, Petitjean O. Clinical pharmacokinetics of diacerein. Clin
Pharmacokinet. 1998 ;35(5):347-59. DOI: 10.2165/00003088-199835050-00002.
Patil P, Chavanke D, Wagh M. A review on ionotropic gelation method: novel
approach for controlled gastroretentive gelispheres. Int J Pharm Sci. 2012;4(4):27-32.
Haznedar S, Dortunc B. Preparation and in vitro evaluation of Eudragit liposomes
containing acetazolamide. International journal of pharmaceutics. 2004;269(1):131-
DOI:10.1016/j.ijpharm.2003.09.015
Ishak RA, Awad GA, Mortada ND, Nour SA. Preparation, in vitro and in vivo
evaluation of stomach-specific metronidazole-loaded alginate beads as local anti-
Helicobacter pylori therapy. J of control release.2007;119(2):207-14.
DOI:https://doi.org/10.1016/j.jconrel.2007.02.012
Kulkarni AR, Soppimath KS, Aminabhavi TM. Controlled release of diclofenac
sodium from sodium alginate beads crosslinked with glutaraldehyde. Pharmaceutica
Acta Helvetiae. 1999;74(1):29-36. DOI: 10.1016/s0031-6865(99)00015-1
Koudelka S, Turánek J. Liposomal paclitaxel formulations. J Control Release. 2012
;163(3):322-34. DOI:10.1016/j.jconrel.2012.09.006
Yang T, Cui FD, Choi MK, Lin H, Chung SJ, Shim CK, Kim DD. Liposome
formulation of paclitaxel with enhanced solubility and stability. Drug Deliv.
;14(5):301-8.DOI: https://doi.org/10.1080/10717540601098799
Ravar F, Saadat E, Gholami M, Dehghankelishadi P, Mahdavi M, Azami S, Dorkoosh
FA. Hyaluronic acid-coated liposomes for targeted delivery of paclitaxel, in-vitro
characterization and in-vivo evaluation. J Control Release. 2016;229:10-22.
DOI: 10.1016/j.jconrel.2016.03.012
Bao QY, Zhang N, Geng DD, Xue JW, Merritt M, Zhang C, Ding Y. The enhanced
longevity and liver targetability of Paclitaxel by hybrid liposomes encapsulating
Paclitaxel-conjugated gold nanoparticles. Int J Pharm. 2014;477(1-2):408-15.
DOI:10.1016/j.ijpharm.2014.10.040
Veselov VV, Nosyrev AE, Jicsinszky L, Alyautdin RN, Cravotto G. Targeted
Delivery Methods for Anticancer Drugs. Cancers (Basel). 2022;14(3):622.
DOI:10.3390/cancers14030622
Patil P, Singh S, Sarvanan J. Preparation And Evaluation Of Liposomes Of
Flurbiprofen. Int J of Pharm Sci And Res. 2018;9(12):5388-93. DOI:
13040/IJPSR.0975-8232.9(9).3621-37
Trang Le NT, Nguyen NH, Hoang MC, Khoa Nguyen C, Hai Nguyen D, Tran DL.
Preparation of liposomal nanocarrier by extruder to enhance tumor accumulation of
paclitaxel. J of Bioactive and Compatible Polymers. 2022;37(1):3-16. DOI:
https://doi.org/10.1177/08839115211053926
Utreja P, Jain S, Tiwary AK. Localized delivery of paclitaxel using elastic liposomes:
formulation development and evaluation. Drug Delivery. 2011;18 (5): 367-76.
DOI:10.3109/10717544.2011.558527
Gu Z, Da Silva CG, Van der Maaden K, Ossendorp F, Cruz LJ. Liposome-Based
Drug Delivery Systems in Cancer Immunotherapy. Pharmaceutics. 2020;12(11):1054.
doi:10.3390/pharmaceutics12111054
Lakkadwala S, Dos Santos Rodrigues B, Sun C, Singh J. Dual functionalized
liposomes for efficient co-delivery of anti-cancer chemotherapeutics for the treatment
of glioblastoma. J Control Release. 2019;307:247-260.DOI:
1016/j.jconrel.2019.06.033
Koudelka S, Turanek Knotigova P, Masek J, Prochazka L, Lukac R, Miller AD,
Neuzil J, Turanek J. Liposomal delivery systems for anti-cancer analogues of vitamin
E. J Control Release. 2015;207:59-69. DOI: 10.1016/j.jconrel.2015.04.003
Koudelka S, Turánek J. Liposomal paclitaxel formulations. J Control Release.
;163(3):322-34. DOI:10.1016/j.jconrel.2012.09.006
Yang T, Cui FD, Choi MK, Lin H, Chung SJ, Shim CK, Kim DD. Liposome
formulation of paclitaxel with enhanced solubility and stability. Drug Deliv.
;14(5):301-8.DOI: https://doi.org/10.1080/10717540601098799.
Ravar F, Saadat E, Gholami M, Dehghankelishadi P, Mahdavi M, Azami S,
Dorkoosh FA. Hyaluronic acid-coated liposomes for targeted delivery of paclitaxel,
in-vitro characterization and in-vivo evaluation. J Control Release. 2016;229:10-22.
DOI: 10.1002/jcp.29576
Bao QY, Zhang N, Geng DD, Xue JW, Merritt M, Zhang C, Ding Y. The enhanced
longevity and liver targetability of Paclitaxel by hybrid liposomes encapsulating
Paclitaxel-conjugated gold nanoparticles. Int J Pharm. 2014;477(1-2):408-15.
DOI:10.1016/j.ijpharm.2014.10.040
Sparano JA, Wang M, Martino S, et al. Weekly paclitaxel in the adjuvant treatment of
breast cancer [published correction appears in N Engl J Med. 2008 Jul 3;359(1):106]
[published correction appears in N Engl J Med. 2009 Apr 16;360(16):1685]. N Engl J
Med. 2008;358(16):1663-1671. DOI:10.1056/NEJMoa0707056
Patt D, Rembert D, Corzo D. Treatment of metastatic breast cancer with ������-
paclitaxel in the community practice setting: a US Oncology survey. J Community
Support Oncol. 2015;13(5):173-80. DOI: 10.12788/jcso.0132
Olusanya TOB, Haj A RR, Ibegbu DM, Smith JR, Elkordy AA. Liposomal Drug
Delivery Systems and Anticancer Drugs. Molecules. 2018;23(4):907. DOI:
3390/molecules23040907
El Maghraby GM, Arafa MF. Liposomes for Enhanced Cellular Uptake of Anticancer
Agents. Curr Drug Deliv. 2020;17(10):861-873. DOI: 10.3390/molecules23040907.
Fouladi F, Steffen KJ, Mallik S. Enzyme-Responsive Liposomes for the Delivery of
Anticancer Drugs. Bioconjug Chem. 2017;28(4):857-
DOI:https://doi.org/10.1021/acs.bioconjchem.6b00736
Zhang Z, Patel SB, King MR. Micelle-in-Liposomes for Sustained Delivery of
Anticancer Agents That Promote Potent TRAIL-Induced Cancer Cell
Apoptosis. Molecules.2021;26(1):157.DOI:https://doi.org/10.3390/molecules2601015
Alshraim MO, Sangi S, Harisa GI, Alomrani AH, Yusuf O, Badran MM. Chitosan-
Coated Flexible Liposomes Magnify the Anticancer Activity and Bioavailability of
Docetaxel: Impact on Composition. Molecules. 2019; 24(2):250. DOI:
3390/molecules24020250
Olgen S. Overview on Anticancer Drug Design and Development. Curr Med Chem.
;25(15):1704-1719. DOI: 10.2174/0929867325666171129215610
Schlichtig K, Dürr P, Dörje F, Fromm MF. New Oral Anti-Cancer Drugs and
Medication Safety. Dtsch Arztebl Int. 2019;116(46):775-782. DOI:
3238/arztebl.2019.0775
Dordunoo S. K., Burt H. M. Solubility and stability of taxol: effects of buffers and
cyclodextrins. Int. J. Pharm. 1996; 133: 191–201
Schlichtig K, Dürr P, Dörje F, Fromm MF. New Oral Anti-Cancer Drugs and
Medication Safety. Dtsch Arztebl Int. 2019;116(46):775-782.
Rajan K. Verma and Sanjay Garg, “Current Status of Drug Delivery Technologies and
Future Directions, Pharmacutical Technology On-Line,2001;25 (2), 1–14 .
Manivannan R. Recent Advances in Novel Drug Delivery System. IJRAP. 2010;
(2); 316-326
Müller Rainer H, Junghanns Jens-Uwe A H, Nanocrystal technology, drug delivery
and clinical applications, International Journal of Nanomedicine 2008; 3(3):295–309.
DOI: 10.2147/ijn.s595
Shete G, Jain H, Punj D, Prajapat H, Akotiya P, Bansal AK, Stabilizers used in nano-
crystal based drug delivery systems, Int Pharm Excipients Council, 2014; 5(4):184-
Yang T, Cui FD, Choi MK, Lin H, Chung SJ, Shim CK, Kim DD. Liposome
formulation of paclitaxel with enhanced solubility and stability. Drug Deliv.
;14(5):301-8. DOI: https://doi.org/10.1080/10717540601098799.
Shete G, Jain H, Punj D, Prajapat H, Akotiya P, Bansal AK.Stabilizers used in nano-
crystal based drug delivery systems, Int Pharm Excipients Council.2014;5(4):184-
Yang T, Cui FD, Choi MK, Lin H, Chung SJ, Shim CK, Kim DD.Liposome
formulation of paclitaxel with enhanced solubility and stability. Drug
Deliv.2007;14(5):301-8. DOI: https://doi.org/10.1080/10717540601098799.
Das D, Halder D, Bose A, Maji HS, Pal TK. Pharmacokinetic determination of
methylprednisolone in Indian healthy volunteers by LC-MS/MS. J of Med Pharma
and all Sci. 2021;10-I(3)1094:2740-4. doi: 10.22270/jmpas.V10I3.1094.
Das D, Halder D, Sekhar Maji H, Kumar De P, Kumar Pal T. Special emphasis on
bioanalytical method development and validation of an anti-hypertensive drug
azelnidipine by LC-ESI-MS/MS in healthy human volunteer’s blood plasma. Res J
Pharm Technol. 2021;14(7):3571-7. doi: 10.52711/0974-360X.2021.00618.
Das D, Halder D, Sekhar Maji H, Kumar De P, Saha S, Singh N. Introduction of an
innovative approach for bioanalytical method development and validation of
febuxostat by using LC-ESI-MS/MS in Human plasma. Res J Pharm Technol.
;14(8):4060-6. doi: 10.52711/0974-360X.2021.00703.
Das D, Halder D, Bose A, Saha C, Sekhar Maji H, Kumar Pal T. Bioequivalence
study of azelnidipine 16 mg tablet to evaluate pharmacokinetic profile of single dose
in healthy, adult, human volunteers under fasting condition. Int J App Pharm
;13:154-9. doi: 10.22159/ijap.2021v13i4.41331.
Das D, Halder D, Bose A, Shaw TK, Saha C, Kumar DE P, MAJI HS, PAL TK.
Determination of metformin and sitagliptin in healthy human volunteers’ blood
plasma and its bioequivalence study under fasting condition. Int J App Pharm. 2022:
;9;14(6):42-50. doi: 10.22159/ijap.2022v14i6.45140
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