ASSEESSMENT OF CELLULAR TOXICITY ON CANCER CELL LINES USING CAPSAICIN-LOADED PLGA NANOBUBBLES

Authors

  • HEMA KUMAR A. V. Bharatiya Engineering Science and Technology Innovation University (BESTIU), Gownivaripalli, Gorantala Mandal, Anantapur, Andhra Pradesh, India https://orcid.org/0000-0002-1630-9294
  • CHAMAKURI KANTLAM Brilliant Grammar School Educational Society’s Group of Institutions-Integrated Campus (Faculty of Engineering and Faculty of Pharmacy), Hyderabad. Abdullapur (V), Abdullapurmet (M), Rangareddy (Dist), Hyderabad-501505, Telangana, India

DOI:

https://doi.org/10.22159/ijap.2025v17i4.54153

Keywords:

Capsaicin, PLGA nanobubbles, In vitro cell line study, Cancer therapy, Cytotoxicity

Abstract

Objective: This study aims to develop and characterize Capsaicin-Loaded Poly(Lactic-Co-Glycolic Acid) (PLGA) Nanobubbles (CAP-NBs) for targeted drug delivery. The research evaluates the physicochemical properties, drug release profile, cytotoxic effects on cancer cell lines, and formulation stability to assess the potential of CAP-NBs as a controlled and ultrasound-triggered drug delivery system.

Methods: CAP-NBs were formulated using the solvent evaporation method with ultrasound assistance to achieve nanoscale dispersion and high drug entrapment efficiency. Physicochemical characterization was performed using particle size analysis, Polydispersity Index (PDI), Zeta Potential measurement, Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), X-ray Diffraction (XRD), and Scanning Electron Microscopy (SEM) to assess morphology and stability. In vitro drug release studies were conducted to evaluate sustained and ultrasound-triggered release profiles. Cytotoxicity assessments were performed on cancer and normal cell lines to determine the therapeutic efficacy and selectivity of CAP-NBs. Stability studies were conducted over a three-month period to assess long-term formulation viability.

Results: PLGA CAP-NBs were successfully formulated using a solvent evaporation-ultrasonication method, achieving a particle size of 164±6.4 nm, PDI of 0.261±0.09, and ZP of-40.5±6.2 mV, indicating excellent stability. FTIR, DSC, and XRD analyses confirmed successful encapsulation, amorphization, and drug-polymer interactions. In vitro drug release studies revealed sustained and ultrasound-enhanced release, reaching 96.81% cumulative release at 24 h. CAP-NBs demonstrated lower cytotoxicity (IC₅₀ = 73.44 µg/ml for A549; 68.72 µg/ml for A498) compared to the pure drug, suggesting controlled release and reduced acute toxicity.

Conclusion: The study successfully developed and characterized CAP-NBs as a stable and efficient nanocarrier for targeted drug delivery. The formulation exhibited controlled and ultrasound-responsive drug release, along with selective cytotoxic effects against cancer cells. These findings highlight the potential of CAP-NBs for enhanced therapeutic efficacy with reduced systemic toxicity. Further in vivo investigations are warranted to explore their clinical applicability.

References

Govindarajan VS, Sathyanarayana MN. Capsicum production technology chemistry and quality part v. impact on physiology pharmacology nutrition and metabolism; structure pungency pain and desensitization sequences. Crit Rev Food Sci Nutr. 1991 Jun;29(6):435-74. doi: 10.1080/10408399109527536, PMID 2039598.

Caterina MJ, Julius D. The vanilloid receptor: a molecular gateway to the pain pathway. Annu Rev Neurosci. 2001;24(1):487-517. doi: 10.1146/annurev.neuro.24.1.487, PMID 11283319.

Koneru M, Sahu BD, Mir SM, Ravuri HG, Kuncha M, Mahesh Kumar J. Capsaicin the pungent principle of peppers ameliorates alcohol induced acute liver injury in mice via modulation of matrix metalloproteinases. Can J Physiol Pharmacol. 2018 Apr;96(4):419-27. doi: 10.1139/cjpp-2017-0473, PMID 29053935.

Arafath AA, MY, JB. Enhancement of oral bioavailability via solid lipid nanoparticles of anticancer drug dasatinib an in vitro cytotoxicity and pharmacokinetic study. Asian J Pharm Clin Res. 2019 Jun;12(6):143-5. doi: 10.22159/ajpcr.2019.v12i6.33135.

Begum MY, Gudipati PR. Formulation and evaluation of dasatinib loaded solid lipid nanoparticles. Int J Pharm Pharm Sci. 2018 Dec;10(12):14-20. doi: 10.22159/ijpps.2018v10i12.27567.

Kumar MK, Prakash D, Rao VV B. Chitosan nanobubbles development and evaluation for the delivery of sunitinib an anticancer agent. Int J App Pharm. 2022;14(6):58-67. doi: 10.22159/ijap.2022v14i6.45821.

Anil L, Mohandas S. In vitro antioxidant and anticancer activity of macranga peltata leaf extracts on lung cancer cell lines. Int J Curr Pharm Sci. 2023 Apr;15(4):26-32. doi: 10.22159/ijcpr.2023v15i4.3019.

Alley MC, Scudiero DA, Monks A, Hursey ML, Czerwinski MJ, Fine DL. Feasibility of drug screening with panels of human tumor cell lines using a microculture tetrazolium assay. Cancer Res. 1988 Mar;48(3):589-601. PMID 3335022.

Noor F, Niklas J, Muller Vieira U, Heinzle E. An integrated approach to improved toxicity prediction for the safety assessment during preclinical drug development using hep G2 cells. Toxicol Appl Pharmacol. 2009 Feb;237(2):221-31. doi: 10.1016/j.taap.2009.03.011, PMID 19332084.

Konda M, Sampathi S. QbD approach for the development of capsaicin loaded stearic acid grafted chitosan polymeric micelles. Int J App Pharm. 2023 Apr;15(4):131-42. doi: 10.22159/ijap.2023v15i4.48101.

Foudas AW, Kosheleva RI, Favvas EP, Kostoglou M, Mitropoulos AC, Kyzas GZ. Fundamentals and applications of nanobubbles: a review. Chem Eng Res Des. 2023 Jan;189(4):64-86. doi: 10.1016/j.cherd.2022.11.013.

Wang Y, Wang T. Preparation method and application of nanobubbles: a review. Coatings. 2023;13(9):1510. doi: 10.3390/coatings13091510.

Xu JS, Huang J, Qin R, Hinkle GH, Povoski SP, Martin EW. Synthesizing and binding dual mode poly (lactic-co-glycolic acid) (PLGA) nanobubbles for cancer targeting and imaging. Biomaterials. 2010 Jul;31(7):1716-22. doi: 10.1016/j.biomaterials.2009.11.052, PMID 20006382.

Mondal R, Bobde Y, Ghosh B, Giri TK. Development and characterization of a phospholipid complex for effective delivery of capsaicin. Indian J Pharm Sci. 2019 Jun;81(6):1011-9. doi: 10.36468/pharmaceutical-sciences.598.

Mamatha P, Bhikshapathi DV. Preparation and in vitro evaluation of pemigatinib nanosponges tablets by box-behnken design. Int J Pharm Qual Assur. 2023 Sep;14(3):791-800. doi: 10.25258/ijpqa.14.3.56.

Reddy KS, Bhikshapathi D. Design and optimization of DPC-crosslinked HPβCD nanosponges for entrectinib oral delivery: formulation characterization and pharmacokinetic studies. Futur J Pharm Sci. 2024 Mar;10(1):101. doi: 10.1186/s43094-024-00680-8.

Viswaja M, Bhikshapathi DV, Palanati M, Babu AK, Goje A. Formulation and evaluation of ibrutinib nanosponges incorporated tablet. Int J App Pharm. 2023 Feb;15(2):92-7. doi: 10.22159/ijap.2023v15i2.46813.

Viswaja M, Bhikshapathi DV, Sadasivam RK, Goje A, Cheruku S. Formulation and evaluation of liquid based supersaturable self-nanoemulsifying drug delivery system of manidipine. Int J Pharm Sci Drug Res. 2023 Jan-Mar;15(1):80-7. doi: 10.25004/IJPSDR.2023.150112.

Sampathi S, Amancha R, Dodoala SD, Kuchana V. Biodegradable polymeric nanocarriers for oral delivery of antiretroviral drug: pharmacokinetic and in vitro permeability studies. J Appl Pharm Sci. 2021 Apr;11(4):028-39.

Alley MC, Scudiero DA, Monks A, Czerwinski M, Shoemaker R, Boyd MR. Validation of an automated microculture tetrazolium assay (MTA) to assess growth and drug sensitivity of human tumor cell lines. Proc Am Assoc Cancer Res. 1986;27:389-91.

Berridge MV, Herst PM, Tan AS. Tetrazolium dyes as tools in cell biology: new insights into their cellular reduction. Biotechnol Annu Rev. 2005;11:127-52. doi: 10.1016/S1387-2656(05)11004-7, PMID 16216776.

Fotakis G, Timbrell JA. In vitro cytotoxicity assays: comparison of LDH neutral red MTT and protein assay in hepatoma cell lines following exposure to cadmium chloride. Toxicol Lett. 2006 Feb;160(2):171-7. doi: 10.1016/j.toxlet.2005.07.001, PMID 16111842.

Freshney RI. Culture of animal cells: a manual of basic technique and specialized applications. Wiley Blackwell; 2015.

Jin L, Wang T, Zhu ML, Leach MK, Naim YI, Corey JM. Electrospun fibers and tissue engineering. J Biomed Nanotechnol. 2012;8(1):1-9. doi: 10.1166/jbn.2012.1360, PMID 22515089.

Chou TC, Talalay P. Quantitative analysis of dose effect relationships: the combined effects of multiple drugs or enzyme inhibitors. Adv Enzyme Regul. 1984 Feb;22:27-55. doi: 10.1016/0065-2571(84)90007-4, PMID 6382953.

Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983;65(1-2):55-63. doi: 10.1016/0022-1759(83)90303-4, PMID 6606682.

Weigt C, Huebner H, Meier M, Walczak R. Advances in nanomedicine and targeted therapy for cancer. Trends Biotechnol. 2020 Apr;38(4):423-37.

Published

07-07-2025

How to Cite

A. V., H. K., & KANTLAM, C. (2025). ASSEESSMENT OF CELLULAR TOXICITY ON CANCER CELL LINES USING CAPSAICIN-LOADED PLGA NANOBUBBLES. International Journal of Applied Pharmaceutics, 17(4), 145–151. https://doi.org/10.22159/ijap.2025v17i4.54153

Issue

Section

Original Article(s)

Similar Articles

<< < 3 4 5 6 7 > >> 

You may also start an advanced similarity search for this article.