Research Article
BibTex RIS Cite

Preparation, radiolabeling and cell culture studies of chitosan coated PLGA nanoparticles as a potential cancer diagnostic agent

Year 2022, Volume: 26 Issue: 6, 1636 - 1645, 28.06.2025

Meliha Ekinci , A. Alper Öztürk , Derya İlem-özdemir

Abstract

Using the nanoprecipitation process, chitosan coated poly lactic-co-glycolic acid (PLGA) based polymeric nanoparticle formulations of two molecular weights were developed as a possible cancer cell diagnostic agent. Photon correlation spectroscopy was used to measure the particle size, distribution [polydispersity index (PDI)], and zeta potential values of developed nanoparticle formulations. The F1 [low molecular weight PLGA (Resomer® RG 503 H)] and F2 [high molecular weight PLGA (Resomer® RG 504 H)] formulations were then directly labeled with Technetium99m ([ 99mTc]Tc) using stannous salts (chloride) as a reducing agent. The radiochemical purity (RP) and in vitro stability in different mediums of the formulations were assessed using ascending radioactive thin layer chromatography (RTLC) method. The cell incorporation of [ 99mTc]Tc labeled F1 and F2 formulations, as well as Reduced/Hydrolized [ 99mTc]NaTcO4 (R/H-[ 99mTc]NaTcO4) in the MCF-7 (breast cancer cell line) cells, was then assessed. The nanoparticles had a middle size of 408.9±3.626 nm to 421.3±7.205 nm, a PDI value of 0.310±0.055 to 0.330±0.066, and a positive charge of +70.5±1.4 mV to +75.5±3.8 mV, according to the characterization results. F1 and F2 formulations were effectively radiolabeled with [ 99mTc]Tc, and their RP was found to be over 98% in both cases. When compared to [ 99mTc]Tc-F1 (45.091±2.254%) and R/H-[ 99mTc]NaTcO4 (8.527±0.426%), the incorporation percentages of [ 99mTc]Tc-F2 (70.756±3.537%) were shown to be higher in cancer cell lines (breast cancer cells, MCF-7). According to this research, radiolabeled chitosan coated PLGA nanoparticles ([ 99mTc]Tc-F2) could be suggested as promising cancer detection formulations. However, further investigations, such as biodistribution studies, should be performed.

Keywords

chitosan PLGA nanoparticle diagnostic nanosystem technetium-99m radiolabeling cell culture

References

  • [1] Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020;70:7–30. [CrossRef]
  • [2] Singh SK, Singh S, Lillard JW Jr, Singh R. Drug delivery approaches for breast cancer. Int J Nanomedicine. 2017;12:6205–6218. [CrossRef]
  • [3] Lv L, Shi Y, Wu J, Li G. Nanosized drug delivery systems for breast cancer stem cell targeting. Int J Nanomedicine. 2021;16:1487–1508. [CrossRef]
  • [4] Ekinci M, Santos-Oliveira R, İlem-Özdemir D. Biodistribution of 99mTc-PLA/PVA/Atezolizumab nanoparticles for non-small cell lung cancer diagnosis. Eur J Pharm Biopharm. 2022;176:21–31. [CrossRef]
  • [5] Ilem-Ozdemir D, Gundogdu EA, Ekinci M, Ozgenc E, Asikoglu M. Nuclear medicine and radiopharmaceuticals for molecular diagnosis. In: Grumezescu AM (ed). Biomedical Applications of Nanoparticles. 1st ed., Elsevier Inc., 2019, pp. 457–490. [CrossRef]
  • [6] Jain A, Kunduru KR, Basu A, Mizrahi B, Domb AJ, Khan W. Injectable formulations of poly(lactic acid) and its copolymers in clinical use. Adv Drug Deliv Rev. 2016;107:213–227. [CrossRef]
  • [7] Akbaba H, Erel-Akbaba G, Kotmakçı M, Başpınar Y. Enhanced cellular uptake and gene silencing activity of survivin-siRNA via ultrasound-mediated nanobubbles in lung cancer cells. Pharm Res. 2020;37:165. [CrossRef]
  • [8] Ashjari M, Khoee S, Mahdavian AR, Rahmatolahzadeh R. Self-assembled nanomicelles using PLGA-PEG amphiphilic block copolymer for insulin delivery: A physicochemical investigation and determination of CMC values. J Mater Sci Mater Med. 2012;23:943–953. [CrossRef]
  • [9] Ashjari M, Panahandeh F, Niazi Z, Abolhasani MM. Synthesis of PLGA–mPEG star-like block copolymer to form micelle loaded magnetite as a nanocarrier for hydrophobic anticancer drug. J Drug Deliv Sci Technol. 2020;56:101563. [CrossRef]
  • [10] Govindarasu M, Abirami P, Alharthi S, Thiruvengadam M, Rajakumar G, Vaiyapuri M. Synthesis, physicochemical characterization, and in vitro evaluation of biodegradable PLGA nanoparticles entrapped to folic acid for targeted delivery of kaempferitrin. Biotechnol Appl Biochem. 2022. [CrossRef]
  • [11] Fraguas-Sánchez AI, Torres-Suárez AI, Cohen M, Delie F, Bastida-Ruiz D, Yart L, et al. PLGA nanoparticles for the intraperitoneal administration of CBD in the treatment of ovarian cancer: In Vitro and In Ovo assessment. Pharmaceutics. 2020;12:439. [CrossRef]
  • [12] Şenel B, Öztürk AA. New approaches to tumour therapy with siRNA-decorated and chitosan-modified PLGA nanoparticles. Drug Dev Ind Pharm. 2019;45:1835–1848. [CrossRef]
  • [13] Moshiri M, Mehmannavaz F, Hashemi M, Yazdian-Robati R, Shabazi N, Etemad L. Evaluation of the efficiency of simvastatin loaded PLGA nanoparticles against acute paraquat-intoxicated rats. Eur J Pharm Sci. 2022;168:106053. [CrossRef]
  • [14] Sharifianjazi F, Khaksar S, Esmaeilkhanian A, Bazli L, Eskandarinezhad S, Salahshour P, et al. Advancements in fabrication and application of chitosan composites in implants and dentistry: A review. Biomolecules. 2022;12:155. [CrossRef]
  • [15] Yee Kuen C, Masarudin MJ. Chitosan nanoparticle-based system: A new insight into the promising controlled release system for lung cancer treatment. Molecules. 2022;27:473. [CrossRef]
  • [16] Yang F, Cabe M, Nowak HA, Langert KA. Chitosan/poly(lactic-co-glycolic)acid nanoparticle formulations with finely-tuned size distributions for enhanced mucoadhesion. Pharmaceutics. 2022;14:95. [CrossRef]
  • [17] Zare S, Kabiri M, Amini Y, Najafi A, Mohammadpour F, Ayati SH, et al. Immunological assessment of chitosan or trimethyl chitosan-coated PLGA nanospheres containing fusion antigen as the novel vaccine candidates against tuberculosis. AAPS PharmSciTech. 2021;23:15. [CrossRef]
  • [18] Elitez Y, Ekinci M, Ilem-Ozdemir D, Gundogdu E, Asikoglu M. Tc-99m radiolabeled alendronate sodium microemulsion: Characterization and permeability studies across caco-2 cells. Curr Drug Deliv. 2018;15:342–350. [CrossRef]
  • [19] İlem-Özdemir D, Karavana SY, Şenyiğit ZA, Çalışkan Ç, Ekinci M, Asikoglu M, et al. Radiolabeling and cell incorporation studies of gemcitabine HCl microspheres on bladder cancer and papilloma cell line. J Radioanal Nucl Chem. 2016;310:515–522. [CrossRef]
  • [20] Alshamsan A. Nanoprecipitation is more efficient than emulsion solvent evaporation method to encapsulate cucurbitacin I in PLGA nanoparticles. Saudi Pharm J. 2014;22:219–222. [CrossRef]
  • [21] Bilati U, Allémann E, Doelker E. Development of a nanoprecipitation method intended for the entrapment of hydrophilic drugs into nanoparticles. Eur J Pharm Sci. 2005;24:67–75. [CrossRef]
  • [22] Luque-Alcaraz AG, Lizardi-Mendoza J, Goycoolea FM, Higuera-Ciapara I, Argüelles-Monal W. Preparation of chitosan nanoparticles by nanoprecipitation and their ability as a drug nanocarrier. RSC Adv. 2016;6:59250–59256. [CrossRef]
  • [23] Martínez Rivas CJ, Tarhini M, Badri W, Miladi K, Greige-Gerges H, Nazari QA, et al. Nanoprecipitation process: From encapsulation to drug delivery. Int J Pharm. 2017;532:66–81. [CrossRef]
  • [24] Miladi K, Sfar S, Fessi H, Elaissari A. Nanoprecipitation process: from particle preparation to in vivo applications. In: Vauthier C, Ponchel G, editors. Polymer Nanoparticles for Nanomedicines. Springer; 2016. pp. 17–53.
  • [25] Mora-Huertas CE, Fessi H, Elaissari A. Polymer-based nanocapsules for drug delivery. Int J Pharm. 2010;385:113–142. [CrossRef]
  • [26] Martín-Banderas L, Álvarez-Fuentes J, Durán-Lobato M, Prados J, Melguizo C, Fernández-Arévalo M, Holgado MÁ. Cannabinoid derivate-loaded PLGA nanocarriers for oral administration: formulation, characterization, and cytotoxicity studies. Int J Nanomed. 2012;7:5793–5806. [CrossRef]
  • [27] Bhattacharjee S. DLS and zeta potential? What they are and what they are not? J Control Release. 2016;235:337–351. [CrossRef]
  • [28] Zolle U. Technetium-99m Pharmaceuticals: Preparation and Quality Control in Nuclear Medicine. Springer; 2007. [CrossRef]
  • [29] Varani M, Campagna G, Bentivoglio V, Serafinelli M, Martini ML, Galli F, Signore A. Synthesis and biodistribution of 99mTc-labeled PLGA nanoparticles by microfluidic technique. Pharmaceutics. 2021;13:1769. [CrossRef]
  • [30] Farrag NS, Shetta A, Mamdouh W. Green tea essential oil encapsulated chitosan nanoparticles-based radiopharmaceutical as a new trend for solid tumor theranosis. Int J Biol Macromol. 2021;186:811–819. [CrossRef]
  • [31] Ekinci M, Öztürk AA, Santos-Oliveira R, İlem-Özdemir D. The use of Lamivudine-loaded PLGA nanoparticles in the diagnosis of lung cancer: Preparation, characterization, radiolabeling with 99mTc and cell binding. J Drug Deliv Sci Technol. 2022;69:103139. [CrossRef]
  • [32] Ekinci M, Ilem-Ozdemir D, Gundogdu E, Asikoglu M. Methotrexate loaded chitosan nanoparticles: Preparation, radiolabeling and in vitro evaluation for breast cancer diagnosis. J Drug Deliv Sci Technol. 2015;30:107–113. [CrossRef]
  • [33] Ari K, Ucar E, Ichedef C, Kilcar AY, Medine EI, Parlak Y, et al. Tc-99m(I) carbonyl-radiolabeled lipid-based drug carriers for temozolomide delivery and bioevaluation by in vitro and in vivo. Radiochim Acta. 2019;107:1185–1193. [CrossRef]
  • [34] Jackson MR, Bavelaar BM, Waghorn PA, Gill MR, El-Sagheer AH, Brown T, et al. Radiolabeled oligonucleotides targeting the RNA subunit of telomerase inhibit telomerase and induce DNA damage in telomerase-positive cancer cells. Cancer Res. 2019;79:4627–4637. [CrossRef]
  • [35] Bansal A, Pandey MK, Demirhan YE, Nesbitt JJ, Crespo-Diaz RJ, Terzic A, et al. Novel 89Zr cell labeling approach for PET-based cell trafficking studies. EJNMMI Res. 2015;5:19. [CrossRef]
  • [36] de Lima IA, Khalil NM, Tominaga TT, Lechanteur A, Sarmento B, Mainardes RM. Mucoadhesive chitosan-coated PLGA nanoparticles for oral delivery of ferulic acid. Artif Cells Nanomed Biotechnol. 2018;46:993–1002. [CrossRef]
  • [37] Durán-Lobato M, Martín-Banderas L, Gonçalves LMD, Fernández-Arévalo M, Almeida AJ. Comparative study of chitosan- and PEG-coated lipid and PLGA nanoparticles as oral delivery systems for cannabinoids. J Nanopart Res. 2015;17:1–17. [CrossRef]
  • [38] Khan N, Ameeduzzafar, Khanna K, Bhatnagar A, Ahmad FJ, Ali A. Chitosan coated PLGA nanoparticles amplify the ocular hypotensive effect of forskolin: Statistical design, characterization and in vivo studies. Int J Biol Macromol. 2018;116:648–663. [CrossRef]
  • [39] Carvalho PM, Felício MR, Santos NC, Gonçalves S, Domingues MM. Application of light scattering techniques to nanoparticle characterization and development. Front Chem. 2018;6:237. [CrossRef]
  • [40] Kakkar V, Mishra AK, Chuttani K, Kaur IP. Proof of concept studies to confirm the delivery of curcumin loaded solid lipid nanoparticles (C-SLNs) to brain. Int J Pharm. 2013;448:354–359. [CrossRef]
There are 40 citations in total.

Details

Primary Language English
Subjects Radiopharmacy
Journal Section Articles
Authors

Meliha Ekinci

A. Alper Öztürk

Derya İlem-özdemir

Publication Date June 28, 2025
Published in Issue Year 2022 Volume: 26 Issue: 6

Cite

APA Ekinci, M., Öztürk, A. A., & İlem-özdemir, D. (2025). Preparation, radiolabeling and cell culture studies of chitosan coated PLGA nanoparticles as a potential cancer diagnostic agent. Journal of Research in Pharmacy, 26(6), 1636-1645.
AMA Ekinci M, Öztürk AA, İlem-özdemir D. Preparation, radiolabeling and cell culture studies of chitosan coated PLGA nanoparticles as a potential cancer diagnostic agent. J. Res. Pharm. June 2025;26(6):1636-1645.
Chicago Ekinci, Meliha, A. Alper Öztürk, and Derya İlem-özdemir. “Preparation, Radiolabeling and Cell Culture Studies of Chitosan Coated PLGA Nanoparticles As a Potential Cancer Diagnostic Agent”. Journal of Research in Pharmacy 26, no. 6 (June 2025): 1636-45.
EndNote Ekinci M, Öztürk AA, İlem-özdemir D (June 1, 2025) Preparation, radiolabeling and cell culture studies of chitosan coated PLGA nanoparticles as a potential cancer diagnostic agent. Journal of Research in Pharmacy 26 6 1636–1645.
IEEE M. Ekinci, A. A. Öztürk, and D. İlem-özdemir, “Preparation, radiolabeling and cell culture studies of chitosan coated PLGA nanoparticles as a potential cancer diagnostic agent”, J. Res. Pharm., vol. 26, no. 6, pp. 1636–1645, 2025.
ISNAD Ekinci, Meliha et al. “Preparation, Radiolabeling and Cell Culture Studies of Chitosan Coated PLGA Nanoparticles As a Potential Cancer Diagnostic Agent”. Journal of Research in Pharmacy 26/6 (June 2025), 1636-1645.
JAMA Ekinci M, Öztürk AA, İlem-özdemir D. Preparation, radiolabeling and cell culture studies of chitosan coated PLGA nanoparticles as a potential cancer diagnostic agent. J. Res. Pharm. 2025;26:1636–1645.
MLA Ekinci, Meliha et al. “Preparation, Radiolabeling and Cell Culture Studies of Chitosan Coated PLGA Nanoparticles As a Potential Cancer Diagnostic Agent”. Journal of Research in Pharmacy, vol. 26, no. 6, 2025, pp. 1636-45.
Vancouver Ekinci M, Öztürk AA, İlem-özdemir D. Preparation, radiolabeling and cell culture studies of chitosan coated PLGA nanoparticles as a potential cancer diagnostic agent. J. Res. Pharm. 2025;26(6):1636-45.