Nashrieh Shimi va Mohandesi Shimi Iran

Nashrieh Shimi va Mohandesi Shimi Iran

Polycaprolactone Nanocapsules Containing Olaparib as a Sustained-Release Drug Delivery System for Breast Cancer Treatment

Document Type : Research Article

Authors
1 Department of Chemistry, Science and Research Branch, Islamic Azad University, Tehran, I.R.IRAN
2 Faculty of Agriculture and Natural Resources, Payam Noor University, Tehran, I.R.IRAN
3 Faculty of Basic Sciences, Payam Noor University, Tehran, I.R.IRAN
Abstract
Breast cancer is the most prevalent type of cancer in women. Olaparib (OLB) is an approved drug for treating this specific cancer; however, due to its limited water solubility and high dosage requirements, an effective drug delivery system (DDS) is essential. In this study, a novel and efficient DDS for OLB was developed using polycaprolactone (PCL) nanocapsules, and its physical and chemical properties were evaluated over a 40-day period. The nanocapsules achieved a drug loading efficiency of 91%. They exhibited an average particle size of 221 nm, a polydispersity index of 0.196, and a zeta potential of -29.70 mV, indicating the complete stability of the OLB@PCL nanocapsules. TEM images revealed a spherical morphology without any signs of aggregation. Furthermore, after 40 days of storage at room temperature, the nanocapsules remained stable, showing no signs of instability, aggregation, or decomposition. In vitro release profile studies demonstrated the controlled release of OLB from the PCL nanocapsules. Finally, the MTT assay revealed that the OLB@PCL nanocapsules exhibited greater cytotoxic activity against MCF-7 cell lines compared to free OLB, with an IC50 value of 522 μg/mL versus 703 μg/mL, respectively.
Keywords

Subjects


[1] Daughton C.G., Ruhoy I.S., Environmental Footprint of Pharmaceuticals: The Significance of Factors Beyond Direct Excretion to Sewers. Environ. Toxicol. Chem., 28: 2495-2521 (2009).
[2] Alqahtani M.S., Kazi M., Alsenaidy M.A., Ahmad M.Z., Advances in Oral Drug Delivery. Front. Pharmacol., 12: 618411 (2021).
[3] Park K., Controlled Drug Delivery Systems: Past Forward and Future Back. J. Control. Release, 190: 3-8 (2014).
[4] Li C., Wang J., Wang Y., Gao H., Wei G., Huang Y., Jin Y., Recent Progress in Drug DeliveryActa Pharm. Sin. B, 9: 1145-1162 (2019).
[5] Zhang Y., Chan H.F., Leong K.W., Advanced Materials and Processing for Drug Delivery: The Past and the FutureAdv. Drug. Deliv. Rev., 65: 104-120 (2013).
[6] کرمی، محمد حسین؛ عبدوس، مجید؛ کلایی، محمد رضا؛ مرادی، امید. نانو حامل­های پایه کیتوسان برای رهایش داروی ضد سرطان کورکومین: مطالعه مروری. نشریه شیمی و مهندسی شیمی ایران، (4)42: 1-17 (1402).
[7] رضانژاد بردجی، قاسم؛ حسینی، سمانه سادات. سنتز هیدروژل نانوکامپوزیت آهن و بررسی رهایش داروی ضدسرطان دوکسوروبیسین. نشریه شیمی و مهندسی شیمی ایران، (1)38: 67-78 (1398).
[8] حسینی، حمیدرضا ؛عبدوس، مجید؛ گلشکن، مصطفی؛ طهرانی؛ پدارم. طراحی و ترکیب نانوکامپوزیت­های نوین کارآمد Fe3O4@MCM-41/HAP/APTES و CMC/MMT/HAP برای دارورسانی رهایش کنترل شده: تحویل هدفمند تری پاراتاید در مهندسی بافت استخوان. نشریه شیمی و مهندسی شیمی ایران، (3)43: 51-72 (1403).
[9] Tong X., Pan W., Su T., Zhang M., Dong W., Qi X., Recent Advances in Natural Polymer-Based Drug Delivery SystemsReact. Funct. Polym. 148: 104501 (2020).
[10] Rong X., Xie Y., Hao X., Chen T., Wang Y., Liu Y., Applications of Polymeric Nanocapsules in Field of Drug Delivery Systems. Curr. Drug Discov. Technol., 8: 173-187 (2011).
[11] Li M., Shi K., Tang X., Wei J., Cun X., Chen X., Yu, Q., Zhang, Z., He, Q., pH-Sensitive Folic Acid and dNP2 Peptide Dual-Modified Liposome for Enhanced Targeted Chemotherapy of Glioma. Eur. J. Pharm. Sci., 124: 240-248 (2018).
[12] Fouladi F., Steffen K.J., Mallik S., Enzyme-Responsive Liposomes for the Delivery of Anticancer Drugs. Bioconjug. Chem., 28: 857-868 (2017).
[13] Raisi A., Asefnejad A., Shahali M., Sadat Kazerouni Z.A., Kolooshani A., Saber-Samandari S., Kamyab Moghadas B., Khandan A., Preparation, Characterization, and Antibacterial Studies of N, O-Carboxymethyl Chitosan as a Wound Dressing for Bedsore ApplicationArch. Trauma Res9: 181-188 (2020).
[14] Liang H., Mirinejad M. S., Asefnejad A., Baharifar H., Li X., Saber-Samandari S., Toghraei D., Khandan A., Fabrication of Tragacanthin Gum-Carboxymethyl Chitosan Bio-Nanocomposite Wound Dressing with Silver-Titanium Nanoparticles Using Freeze-Drying Method. Mater. Chem. Phys. 279: 125770 (2022).
[15] Foroutan S., Hashemian M., Khosravi M. Ghadiri Nejad M., Asefnejad A., Saber-Samandari S., A Porous Sodium Alginate-CaSiO3 Polymer Reinforced with Graphene Nanosheet: Fabrication and Optimality Analysis. Fibers Polym. 22: 540–549 (2021).
[16] Jamnezhad S., Asefnejad A., Motififard M., Yazdekhasti H., Kolooshani A., Saber-Samandari S., Khandan A., Development and Investigation of Novel Alginate-Hyaluronic Acid Bone Fillers Using Freeze Drying Technique for Orthopedic Field. Nanomed. Res. J. 5: 306-315 (2020).
[18] Englert C., Brendel J.C., Majdanski T.C., Yildirim T., Schubert S., Gottschaldt M., Schubert U.S., Pharmapolymers in the 21st Century: Synthetic Polymers in Drug Delivery ApplicationsProg. Polym. Sci., 87: 107-164 (2018).
[19] Mondal D., Griffith M., Venkatraman S.S., Polycaprolactone-Based Biomaterials for Tissue Engineering and Drug Delivery: Current Scenario and Challenges. Inter. J. Polym. Material. Polym. Biomaterial. 65: 255-265 (2016).
[20] Pawar R., Pathan A., Nagaraj S., Kapare H., Giram P., Wavhale R., Polycaprolactone and Its Derivatives for Drug DeliveryPolym. Adv. Technol. 34: 3296-3316 (2023).
[21] Chang S.H., Lee H.J., Park S., Kim Y., Jeong B. Fast Degradable Polycaprolactone for Drug Delivery. Biomacromol. 19: 2302-2307 (2018).
[22] Łukasiewicz S., Mikołajczyk A., Błasiak E., Fic E., Dziedzicka-Wasylewska M., Polycaprolactone Nanoparticles as Promising Candidates for Nanocarriers in Novel Nanomedicines. Pharmaceutics, 13: 191 (2021).
[23] Sinha V.R., Bansal K., Kaushik R., Kumria R., Trehan A., Poly-ϵ-Caprolactone Microspheres and Nanospheres: An OverviewInt. J. Pharm., 278:1-23 (2004).
[25]  Chang S.H., Lee H.J., Park S., Kim Y., Jeong B., Fast Degradable Polycaprolactone for Drug DeliveryBiomacromol., 19:2302-2307 (2018)
[26] Schlesinger E., Ciaccio N., Desai T.A., Polycaprolactone Thin-Film Drug Delivery Systems: Empirical and Predictive Models for Device Design. Mater. Sci. Eng. C 57: 232-239 (2015).
[27] Ramanujam R., Sundaram B., Janarthanan G., Devendran E., Venkadasalam M., Milton M.J., Biodegradable Polycaprolactone Nanoparticles Based Drug Delivery Systems: A Short ReviewBiosci. Biotechnol. Res. Asia, 15: 679-685 (2018).
[28] Oliveira H.C., Stolf-Moreira R., Martinez C.B., Sousa G.F., Grillo R., De Jesus M.B., Fraceto L.F., Evaluation of the Side Effects of Poly (Epsilon-Caprolactone) Nanocapsules Containing Atrazine Toward Maize Plants. Front. Chem., 3: 61 (2015).
[29] Stevenson J.C., Farmer R.D.T., HRT and Breast Cancer: A Million Women Ride AgainClimacteric23: 226-228 (2020).
[30] Waks A.G., Winer E.P., Breast Cancer Treatment: A Review. Jama, 321:288-300 (2019).
[31] Matulonis U.A., Sood A.K., Fallowfield L., Howitt B.E., Sehouli J., Karlan B.Y., Ovarian CancerNat. Rev. Dis. Primers, 2: 1-22 (2016).
[32] Sharma G.N., Dave R., Sanadya J., Sharma P., Sharma K., Various Types and Management of Breast Cancer: An OverviewJ. Adv. Pharm. Technol. Res1: 109 (2010).
[35] Chen Y., Zhang L., Hao Q., Olaparib: a Promising PARP Inhibitor in Ovarian Cancer TherapyArch. Gynecol. Obstet288: 367-374 (2013).
[36] Taylor A.M., Chan D.L.H., Tio M., Patil S.M., Traina T.A., Robson M.E., Khasraw M., PARP (Poly ADP‐Ribose Polymerase) Inhibitors for Locally Advanced or Metastatic Breast CancerCochrane Database Syst. Rev. 4: 11395 (2021).
[37] Sun K., Mikule K., Wang Z., Poon G., Vaidyanathan A., Smith G., Zhang Z.Y., Hanke J., Ramaswamy S., Wang J., A Comparative Pharmacokinetic Study of PARP Inhibitors Demonstrates Favorable Properties for Niraparib Efficacy in Preclinical Tumor Models. Oncotarget, 9: 37080 (2018).
[39] Diyanat M., Saeidian H., Baziar S., Mirjafary Z., Preparation and Characterization of Polycaprolactone Nanocapsules Containing Pretilachlor as Herbicide Nanocarrier. Environ. Sci. Pollut. Res., 26: 21579-21588 (2019).
[40] Mahmoudi M., Saeidian H., Mirjafary Z., Mokhtari J., Preparation and Characterization of Memantine Loaded Polycaprolactone Nanocapsules for Alzheimer’s Disease. J. Porous Mater28: 205-212 (2021).
[43] Grillo R., dos Santos N.Z.P., Maruyama C.R., Rosa A.H., de Lima R., Fraceto L.F., Poly (ɛ-Caprolactone) Nanocapsules as Carrier Systems for Herbicides: Physico-Chemical Characterization and Genotoxicity EvaluationJ. Hazard. Mater., 231: 1-9 (2012).
[44] Kusuma S.A.F., Parwati I., Subroto T., Rukayadi Y., Fadhlillah M., Rizaludin A., Comparison of Simple and Rapid Extracting Methods of Free-Tags Mycobacterium Tuberculosis Protein 64 Recombinant Protein from Polyacrylamide Gel: Electroelution and the Optimized Passive Elution. J. Adv. Pharm. Technol. Res., 12: 180-184 (2021).
[45] Sargazi S., Kooshkaki O., Reza J.Z., Saravani R., Jaliani H.Z., Mirinejad S., Meshkini F., Mild Antagonistic Effect of Valproic Acid in Combination with AZD2461 in MCF-7 Breast Cancer CellsMed. J. Islam Repub. Iran33: 29 (2019).
[46] Danaei M., Dehghankhold M., Ataei S., Hasanzadeh Davarani F., Javanmard R., Dokhani A., Mozafari M.R., Impact of Particle Size and Polydispersity Index on the Clinical Applications of Lipidic Nanocarrier SystemsPharm. 10: 57 (2018).
[47] Hunter RJ, ed. Colloid Science: Zeta Potential in Colloid Science: Principles and Applications. London: Academic Press, (1981).
[48] Anwer M.K., Ali E.A., Iqbal M., Ahmed M.M., Aldawsari M.F., Saqr A.A., Alalaiwe A., Soliman G.A., Development of Chitosan-Coated PLGA-Based Nanoparticles for Improved Oral Olaparib Delivery: In Vitro Characterization, and in Vivo Pharmacokinetic Studies. Processes, 10: 1329 (2022).
[49] Ghasemi M., Turnbull T., Sebastian S., Kempson I., The MTT Assay: Utility, Limitations, Pitfalls, and Interpretation in Bulk and Single-Cell Analysis. Int. J. Mol. Sci. 22: 12827 (2021).