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Current Nanomaterials

Editor-in-Chief

ISSN (Print): 2405-4615
ISSN (Online): 2405-4623

Research Article

Preparation, Optimization, and in-vitro Release Study of Abemaciclib-Loaded Chitosan Nanocarrier as a New Approach for Breast Cancer Treatment

Author(s): Mohammed Mohanad Ali, Samer Hasan Hussein-Al-Ali* and Mike Kh. Haddad

Volume 10, Issue 2, 2025

Published on: 13 February, 2024

Page: [217 - 232] Pages: 16

DOI: 10.2174/0124054615288714240110072000

Price: $65

Abstract

Abemaciclib (Abm) is a CDK inhibitor that specifically targets the CDK4/6 cell cycle pathway and has potential anticancer activity. Unfortunately, it has a low solubility and dissolution rate.

Aim: The aim of this study is to enhance the solubility of Abm by loading it onto a chitosan (CS) polymer.

Method: Polymer nanoparticle (NP) and Abm-CSNPs nanocomposites were prepared. Minitab 18 software was used to design 18 run samples to study the effects of CS, tripolyphosphate, and pH as independent variables on the loading efficiency and particle size (dependent variable). The response surface methodology (RSM) was also used to determine how the variables affected the response. The graphical analysis used surface plots, main effects plots, contour plots, and interaction graphs. The study includes F values, p values, variance inflation factors (VIFs), adjusted sums of square (Adj SSs), adjusted mean squares (Adj MSs) and square error of the coefficient (SE Coef). The carriers and loaded samples were also examined using the results of tests, including Fourier transform infrared spectroscopy, X-ray diffraction, and scanning electron microscopy. Furthermore, the release of Abm from Abm-CSNPs nanocomposite was studied in vitro.

Results: The results revealed an ability to produce particle sizes ranging from (168-192) nm and loading efficiencies from (56.7-62.1).

Conclusion: Abm-CSNPs nanocomposite may be used as an alternative drug delivery system for Abm to increase the release time of Abm to 1400 minutes.

Keywords: Abemaciclib, optimization, nanocomposites, release study, breast cancer treatment, chitosan.

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[1]
Basati G, Saffari-Chaleshtori J, Abbaszadeh S, Asadi-Samani M, Ashrafi-Dehkordi K. Molecular dynamics mechanisms of the inhibitory effects of abemaciclib, hymenialdisine, and indirubin on CDK-6. Curr Drug Res Rev 2019; 11(2): 135-41.
[http://dx.doi.org/10.2174/2589977511666191018180001] [PMID: 31875784]
[2]
Sammons SL, Topping DL, Blackwell KLHR. +, HER2-advanced breast cancer and CDK4/6 inhibitors: mode of action, clinical activity, and safety profiles. Curr Cancer Drug Targets 2017; 17(7): 637-49.
[PMID: 28359238]
[3]
Ates-Alagoz Z, Hassan MA-K. Cyclin-dependent kinase 4/6 inhibitors against breast cancer. Mini Rev Med Chem 2023; 23(4): 412-28.
[http://dx.doi.org/10.2174/1389557522666220606095540] [PMID: 35670349]
[4]
Martin JM, Goldstein LJ. Profile of abemaciclib and its potential in the treatment of breast cancer. OncoTargets Ther 2018; 11: 5253-9.
[http://dx.doi.org/10.2147/OTT.S149245] [PMID: 30214230]
[5]
Kim ES. Abemaciclib: First global approval. Drugs 2017; 77(18): 2063-70.
[http://dx.doi.org/10.1007/s40265-017-0840-z] [PMID: 29128965]
[6]
Ansarinik Z, Kiyani H, Yoosefian M. Investigation of self-assembled poly(ethylene glycol)-poly(L-lactic acid) micelle as potential drug delivery system for poorly water soluble anticancer drug abemaciclib. J Mol Liq 2022; 365: 120192.
[http://dx.doi.org/10.1016/j.molliq.2022.120192]
[7]
Kakran M, Li L, Müller RH. Overcoming the challenge of poor drug solubility. Pharm Eng 2012; 32(4): 1-7.
[8]
Chowdary K. Recent research on formulation development of BCS class II drugs–A review. Int Res J Pharm Appl Sci 2013; 3(1): 173-81.
[9]
Kawabata Y, Wada K, Nakatani M, Yamada S, Onoue S. Formulation design for poorly water-soluble drugs based on biopharmaceutics classification system: Basic approaches and practical applications. Int J Pharm 2011; 420(1): 1-10.
[http://dx.doi.org/10.1016/j.ijpharm.2011.08.032] [PMID: 21884771]
[10]
Buniyamin I, Akhir RM, Asli NA, Khusaimi Z, Malek MF, Mahmood MR. Nanotechnology applications in biomedical systems. Curr Nanomater 2022; 7(3): 167-80.
[http://dx.doi.org/10.2174/2405461507666220301121135]
[11]
Sarmah P, Choudhary B. Nanomaterials for targeted delivery of anticancer drugs: An overview. Curr Nanomater 2022; 7(1): 31-9.
[http://dx.doi.org/10.2174/2405461506666210119095130]
[12]
Mehata AK, Dehari D, Gupta A, Rabin DC, Miya A. Multifunctional liquid crystal nanoparticles for cancer therapy. Curr Nanomater 2021; 6(1): 4-16.
[http://dx.doi.org/10.2174/2405461506666210118114851]
[13]
Jha S, Malviya R. Role of nanostructured biomaterials in the treatment and diagnosis of biological disorder. Curr Nanomater 2021; 6(1): 23-30.
[http://dx.doi.org/10.2174/2405461505999201027214348]
[14]
Yusuf A, Almotairy ARZ, Henidi H, Alshehri OY, Aldughaim MS. Nanoparticles as drug delivery systems: A review of the implication of nanoparticles’ physicochemical properties on responses in biological systems. Polymers 2023; 15(7): 1596.
[http://dx.doi.org/10.3390/polym15071596] [PMID: 37050210]
[15]
Begum MY. Advanced modeling based on machine learning for evaluation of drug nanoparticle preparation via green technology: Theoretical assessment of solubility variations. Case Stud Therm Eng 2023; 45: 103029.
[http://dx.doi.org/10.1016/j.csite.2023.103029]
[16]
Wais U, Jackson AW, He T, Zhang H. Nanoformulation and encapsulation approaches for poorly water-soluble drug nanoparticles. Nanoscale 2016; 8(4): 1746-69.
[http://dx.doi.org/10.1039/C5NR07161E] [PMID: 26731460]
[17]
Guo S, Huang L. Nanoparticles containing insoluble drug for cancer therapy. Biotechnol Adv 2014; 32(4): 778-88.
[http://dx.doi.org/10.1016/j.biotechadv.2013.10.002] [PMID: 24113214]
[18]
Wei W, Lu M, Xu W, Polyakov NE, Dushkin AV, Su W. Preparation of protamine-hyaluronic acid coated core-shell nanoparticles for enhanced solubility, permeability, and oral bioavailability of decoquinate. Int J Biol Macromol 2022; 218: 346-55.
[http://dx.doi.org/10.1016/j.ijbiomac.2022.07.152] [PMID: 35878671]
[19]
Kong Y, Wang W, Wang C, Li L, Peng D, Tian B. Supersaturation and phase behavior during dissolution of amorphous solid dispersions. Int J Pharm 2023; 631: 122524.
[http://dx.doi.org/10.1016/j.ijpharm.2022.122524] [PMID: 36549404]
[20]
Correa Soto CE, Gao Y, Indulkar AS, Ueda K, Zhang GGZ, Taylor LS. Impact of surfactants on the performance of clopidogrel-copovidone amorphous solid dispersions: Increased drug loading and stabilization of nanodroplets. Pharm Res 2022; 39(1): 167-88.
[http://dx.doi.org/10.1007/s11095-021-03159-w] [PMID: 35013849]
[21]
Yadav K, Sachan AK, Kumar S, Dubey A. Techniques for increasing solubility: A review of conventional and new strategies. Asian J Pharm Res Dev 2022; 10(2): 144-53.
[http://dx.doi.org/10.22270/ajprd.v10i2.1054]
[22]
Huang H, Zhang Y, Liu Y, Guo Y, Hu C. Influence of intermolecular interactions on crystallite size in crystalline solid dispersions. Pharmaceutics 2023; 15(10): 2493.
[http://dx.doi.org/10.3390/pharmaceutics15102493] [PMID: 37896253]
[23]
Khushbu JR, Jindal R. Thermal stability and optimization of graphene oxide incorporated chitosan and sodium alginate based nanocomposite containing inclusion complexes of paracetamol and β-cyclodextrin for prolonged drug delivery systems. Polym Bull 2023; 80(2): 1751-72.
[http://dx.doi.org/10.1007/s00289-022-04157-7]
[24]
kapoor D, Garg R, Gaur M, et al. Polymeric nanoparticles approach and identification and characterization of novel biomarkers for colon cancer. Results Chem 2023; 6: 101167.
[http://dx.doi.org/10.1016/j.rechem.2023.101167]
[25]
Zou Y, Yue P, Cao H, et al. Biocompatible and biodegradable chitin-based hydrogels crosslinked by BDDE with excellent mechanical properties for effective prevention of postoperative peritoneal adhesion. Carbohydr Polym 2023; 305: 120543.
[http://dx.doi.org/10.1016/j.carbpol.2023.120543] [PMID: 36737194]
[26]
Mukherjee C, Varghese D, Krishna JS, et al. Recent advances in biodegradable polymers – Properties, applications and future prospects. Eur Polym J 2023; 192: 112068.
[http://dx.doi.org/10.1016/j.eurpolymj.2023.112068]
[27]
Pathak R, Bhatt S, Punetha VD, Punetha M. Chitosan nanoparticles and based composites as a biocompatible vehicle for drug delivery: A review. Int J Biol Macromol 2023; 253(Pt 7): 127369.
[http://dx.doi.org/10.1016/j.ijbiomac.2023.127369] [PMID: 37839608]
[28]
Herdiana Y, Husni P, Nurhasanah S, Shamsuddin S, Wathoni N. Chitosan-based nano systems for natural antioxidants in breast cancer therapy. Polymers 2023; 15(13): 2953.
[http://dx.doi.org/10.3390/polym15132953] [PMID: 37447598]
[29]
Mohite P, Rahayu P, Munde S, et al. Chitosan-based hydrogel in the management of dermal infections: A review. Gels 2023; 9(7): 594.
[http://dx.doi.org/10.3390/gels9070594] [PMID: 37504473]
[30]
Kumar V, Sharma N, Janghu P, et al. Synthesis and characterization of chitosan nanofibers for wound healing and drug delivery application. J Drug Deliv Sci Technol 2023; 87: 104858.
[http://dx.doi.org/10.1016/j.jddst.2023.104858]
[31]
Zacaron TM, Silva MLS, Costa MP, et al. Advancements in chitosan-based nanoparticles for pulmonary drug delivery. Polymers 2023; 15(18): 3849.
[http://dx.doi.org/10.3390/polym15183849] [PMID: 37765701]
[32]
Haseli S, Pourmadadi M, Samadi A, et al. A novel pH ‐responsive nanoniosomal emulsion for sustained release of curcumin from a chitosan‐based nanocarrier: Emphasis on the concurrent improvement of loading, sustained release, and apoptosis induction. Biotechnol Prog 2022; 38(5): e3280.
[http://dx.doi.org/10.1002/btpr.3280] [PMID: 35678755]
[33]
Soni SS, D’Elia AM, Alsasa A, et al. Sustained release of drug-loaded nanoparticles from injectable hydrogels enables long-term control of macrophage phenotype. Biomater Sci 2022; 10(24): 6951-67.
[http://dx.doi.org/10.1039/D2BM01113A] [PMID: 36341688]
[34]
Huang H, Lou Z, Zheng S, et al. Intra-articular drug delivery systems for osteoarthritis therapy: shifting from sustained release to enhancing penetration into cartilage. Drug Deliv 2022; 29(1): 767-91.
[http://dx.doi.org/10.1080/10717544.2022.2048130] [PMID: 35261301]
[35]
Yu DG, Wang M, Ge R. Strategies for sustained drug release from electrospun multi‐layer nanostructures. Wiley Interdiscip Rev Nanomed Nanobiotechnol 2022; 14(3): e1772.
[http://dx.doi.org/10.1002/wnan.1772] [PMID: 34964277]
[36]
Abadi AJ, Mirzaei S, Mahabady MK, et al. Curcumin and its derivatives in cancer therapy: Potentiating antitumor activity of cisplatin and reducing side effects. Phytother Res 2022; 36(1): 189-213.
[http://dx.doi.org/10.1002/ptr.7305] [PMID: 34697839]
[37]
Herdiana Y, Wathoni N, Shamsuddin S, Muchtaridi M. Drug release study of the chitosan-based nanoparticles. Heliyon 2022; 8(1): e08674.
[http://dx.doi.org/10.1016/j.heliyon.2021.e08674] [PMID: 35028457]
[38]
Rosen DB, Kvarnhammar AM, Laufer B, et al. TransCon IL-2 β/γ: A novel long-acting prodrug with sustained release of an IL-2Rβ/γ-selective IL-2 variant with improved pharmacokinetics and potent activation of cytotoxic immune cells for the treatment of cancer. J Immunother Cancer 2022; 10(7): e004991.
[http://dx.doi.org/10.1136/jitc-2022-004991] [PMID: 35817480]
[39]
Yuan H, Zhang Z, Hu L. Development and characterization of gastro-floating sustained-release capsule with improved bioavailability of levodopa. Drug Deliv Transl Res 2023; 13(1): 9-17.
[http://dx.doi.org/10.1007/s13346-022-01188-5] [PMID: 35661106]
[40]
Gawade A, Polshettiwar S, Hingalajia H, Prajapati BG, Singh A. Pharmacokinetics and pharmacodynamics of various novel formulations targeting Alzheimer’s disease. In: Alzheimer’s Disease and Advanced Drug Delivery Strategies. Elsevier 2024; pp. 391-402.
[41]
Kousar K, Naseer F, Abduh MS, et al. Green synthesis of hyaluronic acid coated, thiolated chitosan nanoparticles for CD44 targeted delivery and sustained release of Cisplatin in cervical carcinoma. Front Pharmacol 2023; 13: 1073004.
[http://dx.doi.org/10.3389/fphar.2022.1073004] [PMID: 36712656]
[42]
Sabzini M, Pourmadadi M, Yazdian F, Khadiv-Parsi P, Rashedi H. Development of chitosan/halloysite/graphitic carbon nitride nanovehicle for targeted delivery of quercetin to enhance its limitation in cancer therapy: An in vitro cytotoxicity against MCF-7 cells. Int J Biol Macromol 2023; 226: 159-71.
[http://dx.doi.org/10.1016/j.ijbiomac.2022.11.189] [PMID: 36435458]
[43]
Kumar A, Yadav S, Pramanik J, et al. Chitosan-based composites: Development and perspective in food preservation and biomedical applications. Polymers 2023; 15(15): 3150.
[http://dx.doi.org/10.3390/polym15153150] [PMID: 37571044]
[44]
Al-Qubaisi MS, Al-Abboodi AS, Alhassan FH, et al. Preparation, characterization, in vitro drug release and anti-inflammatory of thymoquinone-loaded chitosan nanocomposite. Saudi Pharm J 2022; 30(4): 347-58.
[http://dx.doi.org/10.1016/j.jsps.2022.02.002] [PMID: 35527823]
[45]
Hussein-al-ali SH, Hussein MZ, Ayoub R, Fakurazi S, Abualassal QIA, Al-Dalahmeh Y. Development of new drug formulations: Cetirizine-polymers nanoparticles. Acta Pol Pharm 2021; 78(3)
[46]
Abu Sharar AA, Ramadan SZ, Hussein-Al-Ali SH. Multiobjective optimization of fluphenazine nanocomposite formulation using NSGA-II method. Mater Sci Pol 2021; 39(4): 517-44.
[http://dx.doi.org/10.2478/msp-2021-0042]
[47]
Prajapati BG, Jivani M, Paliwal H. Formulation and optimization of topical nanoemulsion based gel of mometasone furoate using 32 full factorial design. Indian Drugs 2021; 6(06): 19-29.
[48]
Shah S, Ghetiya R, Soniwala M, Chavda J. Development and optimization of inhalable levofloxacin nanoparticles for the treatment of tuberculosis. Curr Drug Deliv 2021; 18(6): 779-93.
[http://dx.doi.org/10.2174/1567201817999201103194626] [PMID: 33155907]
[49]
El Baz AF, Shetaia YMH, Shams EHA, ElMekawy A. Optimization of cellulase production by Trichoderma viride using response surface methodology. Curr Biotechnol 2018; 7(1): 19-25.
[http://dx.doi.org/10.2174/2211550105666160115213402]
[50]
Kumari M, Gupta SK. Response surface methodological (RSM) approach for optimizing the removal of trihalomethanes (THMs) and its precursor’s by surfactant modified magnetic nanoadsorbents (sMNP) - An endeavor to diminish probable cancer risk. Sci Rep 2019; 9(1): 18339.
[http://dx.doi.org/10.1038/s41598-019-54902-8] [PMID: 31797998]
[51]
Huber L. Validation and qualification in analytical laboratories 2007.
[52]
Allen TT, Allen TT. Software overview and methods review: Minitab: statistical quality control and design of experiments and systems. In: Introduction to Engineering Statistics and Lean Six Sigma. 2019; pp. 575-600.
[53]
Lesik SA. Applied statistical inference with MINITAB. CRC Press 2018.
[http://dx.doi.org/10.1201/9780429444951]
[54]
Lewis-Beck MS, Skalaban A. The R-squared: Some straight talk. Polit Anal 1990; 2: 153-71.
[http://dx.doi.org/10.1093/pan/2.1.153]
[55]
Boylan GL, Cho BR. The normal probability plot as a tool for understanding data: A shape analysis from the perspective of skewness, kurtosis, and variability. Qual Reliab Eng Int 2012; 28(3): 249-64.
[http://dx.doi.org/10.1002/qre.1241]
[56]
Abul Kalam M, Khan AA, Khan S, Almalik A, Alshamsan A. Optimizing indomethacin-loaded chitosan nanoparticle size, encapsulation, and release using Box–Behnken experimental design. Int J Biol Macromol 2016; 87: 329-40.
[http://dx.doi.org/10.1016/j.ijbiomac.2016.02.033] [PMID: 26893052]
[57]
Larsen WA, McCleary SJ. The use of partial residual plots in regression analysis. Technometrics 1972; 14(3): 781-90.
[http://dx.doi.org/10.1080/00401706.1972.10488966]
[58]
Tranmer M, Elliot M. Multiple linear regression. CMI 2008; 5(5): 1-5.
[59]
Pokkalla DK, Wang Z, Teoh JC, Poh LH, Lim CT, Quek ST. Soft missing rib structures with controllable negative poisson’s ratios over large strains via isogeometric design optimization. J Eng Mech 2022; 148(11): 04022063.
[http://dx.doi.org/10.1061/(ASCE)EM.1943-7889.0002149]
[60]
Lee R. Statistical design of experiments for screening and optimization. Chemieingenieurtechnik 2019; 91(3): 191-200.
[http://dx.doi.org/10.1002/cite.201800100]
[61]
Muley AB, Ladole MR, Suprasanna P, Dalvi SG. Intensification in biological properties of chitosan after γ-irradiation. Int J Biol Macromol 2019; 131: 435-44.
[http://dx.doi.org/10.1016/j.ijbiomac.2019.03.072] [PMID: 30876903]
[62]
Anand M, Sathyapriya P, Maruthupandy M, Hameedha Beevi A. Synthesis of chitosan nanoparticles by TPP and their potential mosquito larvicidal application. Front Laborat Med 2018; 2(2): 72-8.
[http://dx.doi.org/10.1016/j.flm.2018.07.003]
[63]
Jia Z, Yang C, Zhao F, Chao X, Li Y, Xing H. One-step reinforcement and deacidification of paper documents: Application of Lewis base—Chitosan nanoparticle coatings and analytical characterization. Coatings 2020; 10(12): 1226.
[http://dx.doi.org/10.3390/coatings10121226]
[64]
Anwer MK, Fatima F, Ahmed MM, et al. Abemaciclib-loaded ethylcellulose based nanosponges for sustained cytotoxicity against MCF-7 and MDA-MB-231 human breast cancer cells lines. Saudi Pharm J 2022; 30(6): 726-34.
[http://dx.doi.org/10.1016/j.jsps.2022.03.019] [PMID: 35812154]
[65]
Lei Z, Alwan M, Alamir HTA, et al. Detection of abemaciclib, an anti-breast cancer agent, using a new electrochemical DNA biosensor. Front Chem 2022; 10: 980162.
[http://dx.doi.org/10.3389/fchem.2022.980162] [PMID: 36339035]
[66]
Khorsandi Z, Hajipour AR, Sarfjoo MR, Varma RS. A Pd/Cu-Free magnetic cobalt catalyst for C–N cross coupling reactions: Synthesis of abemaciclib and fedratinib. Green Chem 2021; 23(14): 5222-9.
[http://dx.doi.org/10.1039/D1GC00518A]
[67]
Lustriane C, Dwivany FM, Suendo V, Reza M. Effect of chitosan and chitosan-nanoparticles on post harvest quality of banana fruits. J Plant Biotechnol 2018; 45(1): 36-44.
[http://dx.doi.org/10.5010/JPB.2018.45.1.036]
[68]
Bhumkar DR, Pokharkar VB. Studies on effect of pH on cross-linking of chitosan with sodium tripolyphosphate: A technical note. AAPS PharmSciTech 2006; 7(2): E138-43.
[http://dx.doi.org/10.1208/pt070250] [PMID: 16796367]
[69]
Karimi M, Avci P, Ahi M, Gazori T, Hamblin MR, Naderi-Manesh H. Evaluation of chitosan-tripolyphosphate nanoparticles as a p-shRNA delivery vector: formulation, optimization and cellular uptake study. J Nanopharm Drug Deliv 2013; 1(3): 266-78.
[http://dx.doi.org/10.1166/jnd.2013.1027] [PMID: 26989641]

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