Systematic Scrutinization of Vital factors for the Development of Efficient Cisplatin-Quercetin Loaded Bionanomicelles

Year 2024, , 92 - 107, 01.06.2024

Hardik Rana , Neha Sisodia , Mansi Dholakia Vaishali Gandhi

https://doi.org/10.52794/hujpharm.1298173

Abstract

The present work aims to optimize and assess the Cisplatin (CIS) and Quercetin (QCT)-loaded biodegradable polymeric nanomicelles (PNM). The development of a quantitative method for the estimation of CIS and QCT in pharmaceutical dosage form was another objective. The aluminum plates coated with silica gel F254 used for separation of both the drugs employing Toluene: Methanol: Ethyl acetate: DMF: Triethylamine (5:0.5:3.5:1:1 drop % v/v/v/v/v) as mobile phase. Results of the validation parameter indicate that the developed method was precise, accurate, and robust. CIS and QCT-loaded PNM formulated using solvent evaporation technique employing poly lactic-co-glycolic acid (PLGA) 50:50. The Quality by Design (QbD) was accomplished to identify the critical manufacturing attributes and critical process parameters. Optimization of the formulation was performed by central composite design using particle size and % encapsulation efficiency as dependent variables. The amount of PLGA and Span selected as independent variables. Statistically substantial variables identified using regression analysis and analysis of variance. A diffusion study revealed that optimized nanomicelles were capable to sustain the drug release up to 8h. Zeta sizer, TEM confirmed the stability and nano-sized nanoparticles. CIS-QCT PNM was found to be an alternate route to systemic treatment.

Keywords

cisplatin, quercetin, PLGA 50:50, Bionanomicelles

References

• 1. World Health Organization. WHO Cancer Report 2020 Global Profile. 2020. Available from: https://www.who.int/health- topics/cancer
• 2. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020; 70(1): 7-30. http://dx.doi.org/10.3322/ caac.21590
• 3. Liu B, Yuan Z, Wei CY. Combined microwave ablation and minimally invasive open decompression for managing tho- racic metastasis in breast cancer. Cancer Manag Res. 2018; 10:1397-401. http://dx.doi.org/10.2147/CMAR.S159561
• 4. SIRO Cinepharm USA. Lung Cancer Focus : India, Tracing the Evolution, Prevalence, Distribution, Etiology, Association, Occurrence, Types, Manifestation & Imoact of Lung Cancer in India. 2015.
• 5. Gujral H, Deulkar K. A review of techniques for lung cancer detection. Int J Curr Eng Technol. 2015; 5(3):1597-602.
• 6. Mathur P, Sathishkumar K, Chaturvedi M, et al. Cancer Statis- tics, 2020: Report From National Cancer Registry Programme, India. JCO Glob Oncol. 2020; 6:1063-75. doi: 10.1200/ GO.20.00122.
• 7. Virmani AK, Fong KM, Kodagoda D, et al. Allelotyping demonstrates common and distinct patterns of chromosomal loss in human lung cancer types. Genes Chromosomes Cancer. 1998; 21(4):308-19. http://dx.doi.org/10.1002/(SICI)1098- 2264(199804)21:4<308::AID-GCC4>3.0.CO;2-2
• 8. Wang J, Nie JJ, Guo P, Yan Z, Yu B, Bu W. Rhodium(I) com- plex-based polymeric nanomicelles in water exhibiting coex- istent near-infrared phosphorescence imaging and anticancer activity in vivo. J Am Chem Soc. 2020; 142(6):2709-14. http:// dx.doi.org/10.1021/jacs.9b11013
• 9. Gadgeel SM, Ramalingam SS, Kalemkerian GP. Treatment of lung cancer. Radiol Clin North Am. 2012; 50(5):961-74. http:// dx.doi.org/10.1016/j.rcl.2012.06.003
• 10. Levet V, Rosière R, Merlos R, et al. Development of con- trolled-release cisplatin dry powders for inhalation against lung cancers. Int J Pharm. 2016; 515(1-2):209-20. http:// dx.doi.org/10.1016/j.ijpharm.2016.10.019
• 11. Dasari S, Tchounwou PB. Cisplatin in cancer therapy: Molec- ular mechanisms of action. Eur J Pharmacol. 2014; 740:364- 78. http://dx.doi.org/10.1016/j.ejphar.2014.07.025
• 12. Gibellini L, Pinti M, Nasi M, et al. Quercetin and cancer chemoprevention. Evid Based Complement Alternat Med. 2011; 2011: 591356. http://dx.doi.org/10.1093/ecam/neq053
• 13. Rau JL. The inhalation of drugs: Advantages and problems. Respir Care. 2005; 50(3):367-82.
• 14. Sánchez-González PD, López-Hernández FJ, Dueñas M, et al. Differential effect of quercetin on cisplatin-induced toxicity in kidney and tumor tissues. Food Chem Toxicol. 2017; 107(Pt A):226-36. http://dx.doi.org/10.1016/j.fct.2017.06.047
• 15. Garbuzenko OB, Mainelis G, Taratula O, Minko T. Inhalation treatment of lung cancer: the influence of composition, size and shape of nanocarriers on their lung accumulation and retention. Cancer Biol Med. 2014; 11(1):44-55. http://dx.doi. org/10.7497/j.issn.2095-3941.2014.01.004
• 16. Zheng X, Xie J, Zhang X, et al. An overview of polymeric nano micelles in clinical trials and on the market. Chin Chem Lett 2021. 32(1):243-57. http://dx.doi.org/10.1016/j. cclet.2020.11.029
• 17. Rassu G, Pavan B, Mandracchia D, et al. Polymeric nano mi- celles based on inulin D α-tocopherol succinate for the treat- ment of diabetic retinopathy. J Drug Deliv Sci Technol. 2021; 61:102286. http://dx.doi.org/10.1016/j.jddst.2020.102286
• 18. Wang AZ, Langer R, Farokhzad OC. Nanoparticle delivery of cancer drugs. Annu Rev Med. 2012; 63:185-98. http://dx.doi. org/10.1146/annurev-med-040210-162544
• 19. Jeetah R, Bhaw-Luximon A, Jhurry D. Polymeric nanomicelles for sustained delivery of anti-cancer drugs. Mutat Res. 2014; 768:47-59. http://dx.doi.org/10.1016/j.mrfmmm.2014.04.009
• 20. Kanazawa T, Taki H, Okada H. Nose-to-brain drug delivery system with ligand/cell-penetrating peptide-modified poly - meric nano-micelles for intracerebral gliomas. Eur J Pharm Biopharm. 2020; 152:85-94. http://dx.doi.org/10.1016/j. ejpb.2020.05.001
• 21. Jahan F, Zaman S. Mapping the potential of thiolated plu- ronic based nanomicelles for the safe and targeted delivery of vancomycin against staphylococcal blepharitis. J Drug Deliv Sci Technol. 2020; 61:102220. http://dx.doi.org/10.1016/j. jddst.2020.102220
• 22. Farhadi E, Kobarfard F, H Shirazi F. FTIR Biospectroscopy in- vestigation on cisplatin cytotoxicity in three pairs of sensitive and resistant cell line. Iran J Pharm Res. 2016; 15(1):213-20.
• 23. Kumari A, Yadav SK, Pakade YB, Singh B, Yadav SC. Devel- opment of biodegradable nanoparticles for delivery of querce- tin. Colloids Surf B Biointerfaces. 2010; 80(2):184-92. http:// dx.doi.org/10.1016/j.colsurfb.2010.06.002
• 24. Vaghani D, Patel A, Thakkar V, Gohel M, Lalji B, Gandhi T. Exploring polymeric nano-particles as targeted pulmonary delivery of rifampicin, ethambutol and ofloxacin against inh- resistant tuberculosis. J Lung Pulm Respir Res. 2017; 4(1):1- 13. http://dx.doi.org/10.15406/jlprr.2017.04.00116
• 25. Mathur P, Saini S, Paul E, Sharma C, Mehtani P. Endophytic fungi mediated synthesis of iron nanoparticles: Characteriza- tion and application in methylene blue decolorization. Curr Res Green Sustain Chem. 2021; 4:100053. http://dx.doi. org/10.1016/j.crgsc.2020.100053
• 26. Aziz A, Ali N, Khan A, et al. Chitosanzinc sulfide nanoparti- cles, characterization and their photocatalytic degradation ef- ficiency for azo dyes. Int J Biol Macromol. 2020; 153:502-12. http://dx.doi.org/10.1016/j.ijbiomac.2020.02.310
• 27. Basotra M, Singh S K, Gulati M. Development and validation of a simple and sensitive spectrometric method for estimation of cisplatin hydrochloride in tablet dosage forms : Applica- tion to dissolution studies. ISRN Anal Chem. 2013. https://doi. org/10.1155/2013/936254
• 28. Motisariya MH, Patel KG, Shah PA. Validated stability-indi- cating high performance thin layer chromatographic method for determination of ivabradine hydrochloride in bulk and marketed formulation : An application to kinetic study. Bull Fac Pharm Cairo Univ. 2013; 51(2):233-41. http://dx.doi. org/10.1016/j.bfopcu.2013.07.001
• 29. Shah P, Patel J, Patel K, Gandhi T. Development and valida- tion of an hptlc method for the simultaneous estimation of clonazepam and paroxetine hydrochloride using a DOE ap- proach. J Taibah Univ Sci. 2017; 11(1):121-32. http://dx.doi. org/10.1016/j.jtusci.2015.11.004
• 30. Elkhoudary MM, Selim BM, AbdelSalam RA, Hadad GM, El-Gindy A. Development and validation of a simple HPTLC method for the determination of new hepatitis C Subtype 4 antiviral agents in their tablet dosage form. J Planar Chroma- togr Mod TLC. 2020; 33(1):71-7. http://dx.doi.org/10.1007/ s00764-019-00006-y
• 31. Ahmad W, Husain I, Ahmad N, et al. Box–behnken supported development and validation of robust HPTLC Method: An ap- plication in estimation of punarnavine in leaf, stem, and their Callus of Boerhavia diffusa linn. 3 Biotech. 2020; 10(4):1-10. doi: 10.1007/s13205-020-2154-1
• 32. Emam AA, Naguib IA, Hassan ES, Abdelaleem EA. De- velopment and validation of RP-HPLC and an ecofriendly HPTLC method for simultaneous determination of felodipine and metoprolol succinate, and their major metabolites in hu- man spiked plasma. J AOAC Int. 2020; 103(4):966-71. http:// dx.doi.org/10.1093/jaoacint/qsz040
• 33. Thomas AB, Patil SD, Nanda RK, Kothapalli LP, Bho- sle SS, Deshpande AD. Stability-indicating HPTLC method for simultaneous determination of nateglinide and met- formin hydrochloride in pharmaceutical dosage form. Saudi Pharm J. 2011;19(4): 221-31. http://dx.doi.org/10.1016/j. jsps.2011.06.005
• 34. Mistry NN, Shah P, Patel K, Hingorani L. Simultaneous estimation of stigmasterol and withaferin A in union total herbal formulation using validated HPTLC method. J Appl Pharm Sci. 2015; 5(08):159-66. http://dx.doi.org/10.7324/ JAPS.2015.50825
• 35. Ahmad A, Amir M, Alshadidi AA, Hussain MD, Haq A, Kazi M. Central composite design expert-supported develop- ment and validation of HPTLC method: Relevance in quan- titative evaluation of protopine in Fumaria indica. Saudi Pharm J. 2020; 28(4):487-94. http://dx.doi.org/10.1016/j. jsps.2020.02.011
• 36. Kekre VA, Walode SG. Validated Hptlc Method for Estima- tion of Curcumin Content in Dietary Supplement. IJPRS. 2012; 3(10):3796-800. http://dx.doi.org/10.13040/IJP- SR.0975-8232.3(10).3796-00
• 37. Patel RB, Patel MR, Patni NR, Agrawal V. Efinaconazole: DoE-supported development and validation of a quantitative HPTLC method and its application for the assay of drugs in so- lution and microemulsion-based formulations. Anal Methods. 2020; 12(10):1380-8. http://dx.doi.org/10.1039/C9AY02599E
• 38. Syed HK, Liew KB, Loh GO, Peh KK. Stability indicating HPLC-UV method for detection of curcumin in Curcuma longa extract and emulsion formulation. Food Chem. 2015; 170:321-6. http://dx.doi.org/10.1016/j.foodchem.2014.08.066
• 39. Alam P, Ezzeldin E, Iqbal M, et al. Ecofriendly densitometric RP-HPTLC method for determination of rivaroxaban in na- noparticle formulations using green solvents. RSC Advances. 2020; 10(4):2133-40. http://dx.doi.org/10.1039/C9RA07825H
• 40. BinduG, Ravi Kiran Suripeddi, Development and validation of HPTLC method for identification and quantification of sterols from leaves of Erythroxylum Monogynum Roxb. and in vitro evaluation of antioxidant and anti-glycation activi- ties. S Afr J Bot. 2021; 137:24-34. http://dx.doi.org/10.1016/j. sajb.2020.10.005
• 41. Shewiyo DH, Kaale E, Risha PG, Dejaegher B, Smeyers- Verbeke J, Vander Heyden Y. HPTLC methods to assay active ingredients in pharmaceutical formulations: A review of the method development and validation steps. J Pharm Biomed Anal. 2012; 66:11-23. http://dx.doi.org/10.1016/j. jpba.2012.03.034
• 42. ICH topic Q2 (R1) validation of analytical procedures : Text and methodology. Int Conf Harmon. 2005; 1-17. Available from: https://doi.org/http://www.ich.org/fileadmin/Public_ Web_Site/ICH_Products/Guidelines/Quality/Q2_R1/Step4/ Q2_R1__Guideline.pdf
• 43. Hu X, Han R, Quan LH, Liu CY, Liao YH. Stabilization and sustained release of zeylenone, a soft cytotoxic drug, within polymeric micelles for local antitumor drug delivery. Int J Pharm. 2013; 450(1-2):331-7. http://dx.doi.org/10.1016/j.ijp- harm.2013.04.007
• 44. Szczęch M, Szczepanowicz K. Polymeric core-shell nanopar- ticles prepared by spontaneous emulsification solvent evapo - ration and functionalized by the layer-by-layer method. Nano- materials (Basel). 2020; 10(3):5-8. http://dx.doi.org/10.3390/ nano10030496
• 45. Jia F, Li Y, Lu J, Deng X, Wu Y. Amphiphilic block copoly- mers-guided strategies for assembling nanoparticles: From ba- sic construction methods to bioactive agent delivery applica- tions. ACS Appl Bio Mater. 2020; 3(10):6546-55. http://dx.doi. org/10.1021/acsabm.0c01039
• 46. Gregg Claycamp H. Perspective on quality risk management of pharmaceutical quality. Drug Inf J. 2007; 41(3): 353-67. http://dx.doi.org/10.1177/009286150704100309
• 47. Dave VS, Fahmy RM, Bensley D, Hoag SW. Eudragit(®) RS PO/RL PO as rate-controlling matrix-formers via roller compaction: Influence of formulation and process variables on functional attributes of granules and tablets. Drug Dev Ind Pharm. 2012; 38(10):1240-53. http://dx.doi.org/10.3109/0363 9045.2011.645831
• 48. Dave VS, Fahmy RM, Hoag SW. Investigation of the physical- mechanical properties of Eudragit(®) RS PO/RL PO and their mixtures with common pharmaceutical excipients. Drug Dev Ind Pharm. 2013; 39(7):1113-25. http://dx.doi.org/10.3109/03 639045.2012.714786
• 49. A Review of: “ Introduction to Quality Control. ” By Kaoru Ishikawa. Translated by J. H. Loftus (Chapman and Hall, Lon- don, 1991). Int J Prod Res. 1992; 30(12):2952-2. http://dx.doi. org/10.1080/00207549208948202
• 50. Stamatis DH. Failure mode and effect analysis FMEA from the- ory to execution. 2nd ed. Milwaukee: ASQ Quality Press 2003.
• 51. Mahdizadeh M, Zamanzade E. A new reliability measure in ranked set sampling. Stat Hefte. 2018; 59(3):861-91. http:// dx.doi.org/10.1007/s00362-016-0794-3
• 52. Zamanzade E, Mahdizadeh M. Using ranked set sampling with extreme ranks in estimating the population proportion. Stat Methods Med Res. 2020; 29(1):165-77. http://dx.doi. org/10.1177/0962280218823793
• 53. Fahmy R, Kona R, Dandu R, Xie W, Claycamp G, Hoag SW. Quality by design I: Application of failure mode effect analy- sis (FMEA) and Plackett-Burman design of experiments in the identification of “main factors” in the formulation and process design space for roller-compacted ciprofloxacin hydrochlo - ride immediate-release tablets. AAPS PharmSciTech. 2012; 13(4):1243-54. http://dx.doi.org/10.1208/s12249-012-9844-x
• 54. Gurram RK, Gandra S, Shastri NR. Design and optimiza- tion of disintegrating pellets of MCC by non-aqueous extru- sion process using statistical tools. Eur J Pharm Sci. 2016; 84(1):146-56. http://dx.doi.org/10.1016/j.ejps.2016.01.021
• 55. Bei YY, Zhou XF, You BG, et al. Application of the central composite design to optimize the preparation of novel mi- celles of harmine. Int J Nanomedicine. 2013; 8:1795-808. http://dx.doi.org/10.2147/IJN.S43555
• 56. Kollipara S, Bende G, Movva S, Saha R. Application of ro- tatable central composite design in the preparation and opti- mization of poly(lactic-co-glycolic acid) nanoparticles for controlled delivery of paclitaxel. Drug Dev Ind Pharm. 2010; 36(11):1377-87. http://dx.doi.org/10.3109/03639045.2010.48 7263
• 57. Singh B, Chakkal SK, Ahuja N. Formulation and optimization of controlled release mucoadhesive tablets of atenolol using response surface methodology. AAPS PharmSciTech. 2006; 7(1):E3. http://dx.doi.org/10.1208/pt070103
• 58. Zhang Z, Feng SS. The drug encapsulation efficiency, in vitro drug release, cellular uptake and cytotoxicity of paclitaxel- loaded poly(lactide)-tocopheryl polyethylene glycol succinate nanoparticles. Biomaterials. 2006; 27(21):4025-33. http:// dx.doi.org/10.1016/j.biomaterials.2006.03.006
• 59. Praphakar RA, Munusamy MA, Rajan M. Development of extended-voyaging antioxidant linked amphiphilic poly- meric nanomicelles for anti-tuberculosis drug delivery. Int J Pharm. 2017; 524(1-2):168-77. http://dx.doi.org/10.1016/j. ijpharm.2017.03.089
• 60. Sugihara K, Nakano S, Koda M, Tanaka K, Fukuishi N, Gemba M. Stimulatory effect of cisplatin on production of lipid per- oxidation in renal tissues. Jpn J Pharmacol. 1987; 43(3):247- 52. http://dx.doi.org/10.1016/S0021-5198(19)43504-X
• 61. Sezgin Z, Yüksel N, Baykara T. Preparation and characteriza- tion of polymeric micelles for solubilization of poorly soluble anticancer drugs. Eur J Pharm Biopharm. 2006; 64(3):261-8. http://dx.doi.org/10.1016/j.ejpb.2006.06.003
• 62. Oda CMR, Silva JO, Fernandes RS, et al. Encapsulating paclitaxel in polymeric nano micelles increases antitumor activity and prevents peripheral neuropathy. Biomed Pharmacother. 2020; 132:110864. http://dx.doi.org/10.1016/j.bi- opha.2020.110864
• 63. Rana HB, Raj A, Patel A, Gohel M. Preparation, optimization and in vitro characterization of cisplatin loaded novel poly- meric micelles for treatment of lung cancer. Int J Res Sci Innov. 2016; IV(I):431-41.
• 64. Wei Z, Hao J, Yuan S, et al. Paclitaxel-loaded Pluronic P123/ F127 mixed polymeric micelles: Formulation, optimization and in vitro characterization. Int J Pharm. 2009; 376(1-2):176- 85. http://dx.doi.org/10.1016/j.ijpharm.2009.04.030
• 65. Singhvi G, Singh M. Review : In vitro drug release characteri- zation models. Int J Pharm Stud Res. 2011; II(I):77-84.
• 66. Shrikhande SS, Rao A, Ambekar A, Bajaj AN. Metered dose inhalation formulations of salbutamol sulphate using non- CFC propellant tetrafluoroethane. Int J Pharm Sci Drug Res. 2011; 3(4):292-6.
• 67. Wang J, Kan S, Chen T, Liu J. Application of quality by de- sign (QbD) to formulation and processing of naproxen pel- lets by extrusion-spheronization. Pharm Dev Technol. 2015; 20(2):246-56. http://dx.doi.org/10.3109/10837450.2014.9083 00