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Manuscript ID molecules-3042628
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(/user/chgpwd) Title In vivo toxicity of drug coated chitosan polymeric nanoparticles: A Review
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Journal Molecules (https://www.mdpi.com/journal/molecules)
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Section Natural Polymers Chemistry
(https://www.mdpi.com/journal/molecules/sections/natural_products_chemistry)
Submissions Special Issue Natural Products in Anticancer Activity
Menu (https://www.mdpi.com/journal/molecules/special_issues/1I099R5R4V)
Submit Manuscript Abstract Chitosan nanoparticles has extensively used as polymeric drug carrier in the
development of nanoparticles formulation, due to their potential to improve drug
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delivery, efficacy, and safety. Several toxicity studies have been previously reported
Display Submitted to assess the safety profile of drug coated with chitosan nanoparticles. Toxicity
Manuscripts studies were carried out by various methods such as test animals, interventions,
(/user/manuscripts/status) and different routes of administration. This review aims to summarize research on
the safety profile of drug coated chitosan nanoparticles through general toxicity
Display Co-Authored
tests to obtain the LD50 and NOAEL values and can be used as a database and
Manuscripts references of drug coated chitosan nanoparticles. This review could facilitate other
(/user/manuscripts/co- researcher in determining further development of drug coated chitosan
authored) nanoparticles. The publication from 2014-2024 were obtained from PubMed,
English Editing Scopus, Google Scholar and ScienceDirect, according to inclusion and exclusion
criteria. 16 research articles were included in this review to summarize the in vivo
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toxicity profile of drug coated chitosan nanoparticles. ARRIVE 2.0 was used to
Discount Vouchers evaluate the quality and risk-of-bias of the in vivo toxicity studies. The results
(/user/discount_voucher) demonstrated favorable toxicity profiles, often showing reduced toxicity compared
Invoices to free drugs or substances. Acute toxicity studies consistently reported high LD50
values, frequently exceeding 5000 mg/kg body weight, while subacute studies
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typically revealed no significant adverse effects. Routes of administration varied,
LaTex Word Count including oral, intravenous, intraperitoneal, inhalation, and topical, each showing
(/user/get/latex_word_count) promising safety profiles.
Keywords Drug-coated; Chitosan nanoparticles; Toxicity; LD50, NOAEL.
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Author Information
Submitting Author Muchtaridi Muchtaridi (https://sciprofiles.com/profile/615)
Corresponding Muchtaridi Muchtaridi (https://sciprofiles.com/profile/615)
Author
Author #1 Shela Salsabila
E-Mail [email protected] (co-author email will be published)
Author #2 Misky Aghnia Khairunisa (https://sciprofiles.com/profile/1962386)
E-Mail [email protected] (co-author email will be published)
Author #6 Muchtaridi Muchtaridi (https://sciprofiles.com/profile/615)
E-Mail [email protected] (corresponding author email)
Manuscript Information
Received Date 29 June2024
Revised Date 23 June 2024
Word Count 3038
Page Count 16
APC information
Journal APC: 2,700.00 CHF
IOAP Participant: Padjadjaran University
IOAP Payment: Non-central: Invoiced to author
Funding
Funding Universitas Padjadjaran: 1503/UN6.3.1/PT.00/2024
information
Author Eligible No
Central:
IOAP Discount: 10%
Discount 6c45a9d293c21906 (100.00 CHF) ([email protected])
Vouchers: 7556445a1330dd38 (50.00 CHF) (
[email protected])
Total Payment 2,280.00 CHF
Amount:
Previously Published Papers
Muchtaridi; Subarnas, A.; Apriyantono, A.; Mustarichie, R. Identification of Compounds in the Essential Oil of Nutmeg Seeds
(Myristica fragrans Houtt.) That Inhibit Locomotor Activity in Mice. Int. J. Mol. Sci. 2010, 11, 4771-4781. doi:
10.3390/ijms11114771 (https://doi.org/10.3390/ijms11114771)
Muchtaridi; Diantini, A.; Subarnas, A. Analysis of Indonesian Spice Essential Oil Compounds That Inhibit Locomotor Activity in
Mice. Pharmaceuticals 2011, 4, 590-602. doi: 10.3390/ph4040590 (https://doi.org/10.3390/ph4040590)
Muchtaridi, M.; Yusuf, M.; Diantini, A.; Choi, S.B.; Al-Najjar, B.O.; Manurung, J.V.; Subarnas, A.; Achmad, T.H.; Wardhani, S.R.;
Wahab, H.A. Potential Activity of Fevicordin-A from Phaleria macrocarpa (Scheff) Boerl. Seeds as Estrogen Receptor
Antagonist Based on Cytotoxicity and Molecular Modelling Studies. Int. J. Mol. Sci. 2014, 15, 7225-7249. doi:
10.3390/ijms15057225 (https://doi.org/10.3390/ijms15057225)
Muchtaridi, M.; Syahidah, H.N.; Subarnas, A.; Yusuf, M.; Bryant, S.D.; Langer, T. Molecular Docking and 3D-Pharmacophore
Modeling to Study the Interactions of Chalcone Derivatives with Estrogen Receptor Alpha. Pharmaceuticals 2017, 10, 81. doi:
10.3390/ph10040081 (https://doi.org/10.3390/ph10040081)
Wathoni, N.; Yuniarsih, N.; Cahyanto, A.; Muhctaridi, M. α-Mangostin Hydrogel Film Based Chitosan–Alginate for Recurrent
Aphthous Stomatitis. Appl. Sci. 2019, 9, 5235. doi: 10.3390/app9235235 (https://doi.org/10.3390/app9235235)
Muchtaridi, M.; Sugijanto, M.; Mohd Gazzali, A.; Wahab, H.A. Anti-Neuraminidase Bioactives from Manggis Hutan (Garcinia
celebica L.) Leaves: Partial Purification and Molecular Characterization. Molecules 2020, 25, 821. doi:
10.3390/molecules25040821 (https://doi.org/10.3390/molecules25040821)
Muchtaridi, M.; Fauzi, M.; Khairul Ikram, N.K.; Mohd Gazzali, A.; Wahab, H.A. Natural Flavonoids as Potential Angiotensin-
Converting Enzyme 2 Inhibitors for Anti-SARS-CoV-2. Molecules 2020, 25, 3980. doi: 10.3390/molecules25173980
(https://doi.org/10.3390/molecules25173980)
Wathoni, N.; Sari, D.P.; Suharyani, I.; Motoyama, K.; Mohammed, A.F.A.; Cahyanto, A.; Abdassah, M.; Muchtaridi, M.
Enhancement of α-Mangostin Wound Healing Ability by Complexation with 2-Hydroxypropyl-β-Cyclodextrin in Hydrogel
Formulation. Pharmaceuticals 2020, 13, 290. doi: 10.3390/ph13100290 (https://doi.org/10.3390/ph13100290)
Wathoni, N.; Meylina, L.; Rusdin, A.; Mohammed, A.F.A.; Tirtamie, D.; Herdiana, Y.; Motoyama, K.; Panatarani, C.; Joni, I.M.;
Lesmana, R.; Muchtaridi, M. The Potential Cytotoxic Activity Enhancement of α-Mangostin in Chitosan-Kappa Carrageenan-
Loaded Nanoparticle against MCF-7 Cell Line. Polymers 2021, 13, 1681. doi: 10.3390/polym13111681
(https://doi.org/10.3390/polym13111681)
Herdiana, Y.; Wathoni, N.; Shamsuddin, S.; Joni, I.M.; Muchtaridi, M. Chitosan-Based Nanoparticles of Targeted Drug Delivery
System in Breast Cancer Treatment. Polymers 2021, 13, 1717. doi: 10.3390/polym13111717
(https://doi.org/10.3390/polym13111717)
Muchtaridi, M.; Lestari, D.; Khairul Ikram, N.K.; Gazzali, A.M.; Hariono, M.; Wahab, H.A. Decaffeination and Neuraminidase
Inhibitory Activity of Arabica Green Coffee (Coffea arabica) Beans: Chlorogenic Acid as a Potential Bioactive Compound.
Molecules 2021, 26, 3402. doi: 10.3390/molecules26113402 (https://doi.org/10.3390/molecules26113402)
Herdiana, Y.; Wathoni, N.; Shamsuddin, S.; Muchtaridi, M. α-Mangostin Nanoparticles Cytotoxicity and Cell Death Modalities in
Breast Cancer Cell Lines. Molecules 2021, 26, 5119. doi: 10.3390/molecules26175119
(https://doi.org/10.3390/molecules26175119)
Suharyani, I.; Muchtaridi, M.; Mohammed, A.F.A.; Elamin, K.M.; Wathoni, N.; Abdassah, M. α-Mangostin/γ-Cyclodextrin
Inclusion Complex: Formation and Thermodynamic Study. Polymers 2021, 13, 2890. doi: 10.3390/polym13172890
(https://doi.org/10.3390/polym13172890)
Meylina, L.; Muchtaridi, M.; Joni, I.M.; Mohammed, A.F.A.; Wathoni, N. Nanoformulations of α-Mangostin for Cancer Drug
Delivery System. Pharmaceutics 2021, 13, 1993. doi: 10.3390/pharmaceutics13121993
(https://doi.org/10.3390/pharmaceutics13121993)
Muchtaridi, M.; Nuwarda, R.F.; Ikram, E.H.K.; Abdul Rahim, A.S.; Gazzali, A.M.; Wahab, H.A. Neuraminidase Inhibitor of
Garcinia atroviridis L. Fruits and Leaves Using Partial Purification and Molecular Characterization. Molecules 2022, 27, 949.
doi: 10.3390/molecules27030949 (https://doi.org/10.3390/molecules27030949)
Khutami, C.; Sumiwi, S.A.; Khairul Ikram, N.K.; Muchtaridi, M. The Effects of Antioxidants from Natural Products on Obesity,
Dyslipidemia, Diabetes and Their Molecular Signaling Mechanism. Int. J. Mol. Sci. 2022, 23, 2056. doi: 10.3390/ijms23042056
(https://doi.org/10.3390/ijms23042056)
Dewi, C.; Fristiohady, A.; Amalia, R.; Khairul Ikram, N.K.; Ibrahim, S.; Muchtaridi, M. Signaling Pathways and Natural
Compounds in Triple-Negative Breast Cancer Cell Line. Molecules 2022, 27, 3661. doi: 10.3390/molecules27123661
(https://doi.org/10.3390/molecules27123661)
Ramadhani, D.; Maharani, R.; Gazzali, A.M.; Muchtaridi, M. Cyclic Peptides for the Treatment of Cancers: A Review. Molecules
2022, 27, 4428. doi: 10.3390/molecules27144428 (https://doi.org/10.3390/molecules27144428)
Herdiana, Y.; Wathoni, N.; Shamsuddin, S.; Muchtaridi, M. Cytotoxicity Enhancement in MCF-7 Breast Cancer Cells with
Depolymerized Chitosan Delivery of α-Mangostin. Polymers 2022, 14, 3139. doi: 10.3390/polym14153139
(https://doi.org/10.3390/polym14153139)
Muchtaridi, M.; Amirah, S.R.; Harmonis, J.A.; Ikram, E.H.K. Role of Nuclear Factor Erythroid 2 (Nrf2) in the Recovery of Long
COVID-19 Using Natural Antioxidants: A Systematic Review. Antioxidants 2022, 11, 1551. doi: 10.3390/antiox11081551
(https://doi.org/10.3390/antiox11081551)
Puluhulawa, L.E.; Joni, I.M.; Elamin, K.M.; Mohammed, A.F.A.; Muchtaridi, M.; Wathoni, N. Chitosan–Hyaluronic Acid
Nanoparticles for Active Targeting in Cancer Therapy. Polymers 2022, 14, 3410. doi: 10.3390/polym14163410
(https://doi.org/10.3390/polym14163410)
Budiman, A.; Nurfadilah, N.; Muchtaridi, M.; Sriwidodo, S.; Aulifa, D.L.; Rusdin, A. The Impact of Water-Soluble Chitosan on the
Inhibition of Crystal Nucleation of Alpha-Mangostin from Supersaturated Solutions. Polymers 2022, 14, 4370. doi:
10.3390/polym14204370 (https://doi.org/10.3390/polym14204370)
Maritha, V.; Harlina, P.W.; Musfiroh, I.; Gazzali, A.M.; Muchtaridi, M. The Application of Chemometrics in Metabolomic and
Lipidomic Analysis Data Presentation for Halal Authentication of Meat Products. Molecules 2022, 27, 7571. doi:
10.3390/molecules27217571 (https://doi.org/10.3390/molecules27217571)
Budiman, A.; Citraloka, Z.G.; Muchtaridi, M.; Sriwidodo, S.; Aulifa, D.L.; Rusdin, A. Inhibition of Crystal Nucleation and Growth
in Aqueous Drug Solutions: Impact of Different Polymers on the Supersaturation Profiles of Amorphous Drugs—The Case of
Alpha-Mangostin. Pharmaceutics 2022, 14, 2386. doi: 10.3390/pharmaceutics14112386
(https://doi.org/10.3390/pharmaceutics14112386)
Arifian, H.; Maharani, R.; Megantara, S.; Gazzali, A.M.; Muchtaridi, M. Amino-Acid-Conjugated Natural Compounds: Aims,
Designs and Results. Molecules 2022, 27, 7631. doi: 10.3390/molecules27217631
(https://doi.org/10.3390/molecules27217631)
Nurhidayah, W.; Setyawati, L.U.; Daruwati, I.; Gazzali, A.M.; Subroto, T.; Muchtaridi, M. Future Prospective of
Radiopharmaceuticals from Natural Compounds Using Iodine Radioisotopes as Theranostic Agents. Molecules 2022, 27,
8009. doi: 10.3390/molecules27228009 (https://doi.org/10.3390/molecules27228009)
Mustapa, M.A.; Guswenrivo, I.; Zuhrotun, A.; Ikram, N.K.K.; Muchtaridi, M. Anti-Breast Cancer Activity of Essential Oil: A
Systematic Review. Appl. Sci. 2022, 12, 12738. doi: 10.3390/app122412738 (https://doi.org/10.3390/app122412738)
Meylina, L.; Muchtaridi, M.; Joni, I.M.; Elamin, K.M.; Wathoni, N. Hyaluronic Acid-Coated Chitosan Nanoparticles as an Active
Targeted Carrier of Alpha Mangostin for Breast Cancer Cells. Polymers 2023, 15, 1025. doi: 10.3390/polym15041025
(https://doi.org/10.3390/polym15041025)
Herdiana, Y.; Wathoni, N.; Gozali, D.; Shamsuddin, S.; Muchtaridi, M. Chitosan-Based Nano-Smart Drug Delivery System in
Breast Cancer Therapy. Pharmaceutics 2023, 15, 879. doi: 10.3390/pharmaceutics15030879
(https://doi.org/10.3390/pharmaceutics15030879)
Musfiroh, I.; Kartasasmita, R.E.; Ibrahim, S.; Muchtaridi, M.; Hidayat, S.; Ikram, N.K.K. Stability Analysis of the Asiatic Acid-
COX-2 Complex Using 100 ns Molecular Dynamic Simulations and Its Selectivity against COX-2 as a Potential Anti-
Inflammatory Candidate. Molecules 2023, 28, 3762. doi: 10.3390/molecules28093762
(https://doi.org/10.3390/molecules28093762)
Mustapa, M.A.; Guswenrivo, I.; Zurohtun, A.; Khairul Ikram, N.K.; Muchtaridi, M. Analysis of Essential Oils Components from
Aromatic Plants Using Headspace Repellent Method against Aedes aegypti Mosquitoes. Molecules 2023, 28, 4269. doi:
10.3390/molecules28114269 (https://doi.org/10.3390/molecules28114269)
Budiman, A.; Nurani, N.V.; Laelasari, E.; Muchtaridi, M.; Sriwidodo, S.; Aulifa, D.L. Effect of Drug–Polymer Interaction in
Amorphous Solid Dispersion on the Physical Stability and Dissolution of Drugs: The Case of Alpha-Mangostin. Polymers 2023,
15, 3034. doi: 10.3390/polym15143034 (https://doi.org/10.3390/polym15143034)
Arisanti, C.I.S.; Wirasuta, I.M.A.G.; Musfiroh, I.; Ikram, E.H.K.; Muchtaridi, M. Mechanism of Anti-Diabetic Activity from Sweet
Potato (Ipomoea batatas): A Systematic Review. Foods 2023, 12, 2810. doi: 10.3390/foods12142810
(https://doi.org/10.3390/foods12142810)
Maulidya, V.; Hasanah, A.N.; Rijai, L.; Muchtaridi, M. Quality Control and Authentication of Black Betel Leaf Extract (Piper acre
Blume) from East Kalimantan as an Antimicrobial Agent Using a Combination of High-Performance Liquid Chromatography
and Chemometric Fourier Transform Infrared. Molecules 2023, 28, 5666. doi: 10.3390/molecules28155666
(https://doi.org/10.3390/molecules28155666)
Muchtaridi, M.; Suryani, A.I.; Wathoni, N.; Herdiana, Y.; Mohammed, A.F.A.; Gazzali, A.M.; Lesmana, R.; Joni, I.M.
Chitosan/Alginate Polymeric Nanoparticle-Loaded α-Mangostin: Characterization, Cytotoxicity, and In Vivo Evaluation against
Breast Cancer Cells. Polymers 2023, 15, 3658. doi: 10.3390/polym15183658 (https://doi.org/10.3390/polym15183658)
Herdiana, Y.; Wathoni, N.; Shamsuddin, S.; Muchtaridi, M. Cytotoxicity Enhancement of α-Mangostin with Folate-Conjugated
Chitosan Nanoparticles in MCF-7 Breast Cancer Cells. Molecules 2023, 28, 7585. doi: 10.3390/molecules28227585
(https://doi.org/10.3390/molecules28227585)
Putra, O.N.; Musfiroh, I.; Elisa, S.; Musa, M.; Ikram, E.H.K.; Chaidir, C.; Muchtaridi, M. Sodium Starch Glycolate (SSG) from
Sago Starch (Metroxylon sago) as a Superdisintegrant: Synthesis and Characterization. Molecules 2024, 29, 151. doi:
10.3390/molecules29010151 (https://doi.org/10.3390/molecules29010151)
Rusdin, A.; Mohd Gazzali, A.; Ain Thomas, N.; Megantara, S.; Aulifa, D.L.; Budiman, A.; Muchtaridi, M. Advancing Drug
Delivery Paradigms: Polyvinyl Pyrolidone (PVP)-Based Amorphous Solid Dispersion for Enhanced Physicochemical Properties
and Therapeutic Efficacy. Polymers 2024, 16, 286. doi: 10.3390/polym16020286 (https://doi.org/10.3390/polym16020286)
Muchtaridi, M.; Az-Zahra, F.; Wongso, H.; Setyawati, L.U.; Novitasari, D.; Ikram, E.H.K. Molecular Mechanism of Natural Food
Antioxidants to Regulate ROS in Treating Cancer: A Review. Antioxidants 2024, 13, 207. doi: 10.3390/antiox13020207
(https://doi.org/10.3390/antiox13020207)
Aulifa, D.L.; Amirah, S.R.; Rahayu, D.; Megantara, S.; Muchtaridi, M. Pharmacophore Modeling and Binding Affinity of
Secondary Metabolites from Angelica keiskei to HMG Co-A Reductase. Molecules 2024, 29, 2983. doi:
10.3390/molecules29132983 (https://doi.org/10.3390/molecules29132983)
Arifian, H.; Maharani, R.; Megantara, S.; Ikram, N.K.K.; Muchtaridi, M. Glycine-Conjugated α-Mangostins as Potential Estrogen
Receptor Alpha (ERα) Antagonists through Pharmacophore Modeling, Docking Analysis, and Molecular Dynamics Simulations.
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