Optimization and in vitro evaluation of injectable sustained-release of levothyroxine using PLGA-PEG-PLGA
Open accessAbstract
Abstract Purpose In situ-forming gels (semi-solid state) (ISFGs) are widely used as sustained drug delivery, but they show a high burst release as well. The purpose of the current study is to make triblock that can make a quick gel on injection with a minimum burst release. Methods In this study, to control the release of levothyroxine from ISFG, PLGA-PEG-PLGA (triblock) polymer was used. The melting method was employed to synthesize the triblock via ring-opening polymerization (ROP). Different weight percentages of triblock in the formulation were investigated to reach the minimum initial burst release of levothyroxine from ISFGs.Furthermore, the results of the in-situ forming implant (solid-state) (ISFI) of levothyroxine prepared from PLGA 504 H polymers were compared with ISFG. Results The melting method employed in this study showed a successful ROP of the triblock. As the % triblock concentration was increased from 30 to 50%, the initial burst release decreased significantly. The initial burst release levothyroxine from ISFG (6.52 ± 0.30%) was much lower than the amount of levothyroxine released from ISFI (14.15 ± 0.79%). No cytotoxicity was observed for the sustained-release formulation containing ISFG 50% according to the MTT assay. Conclusion The results indicated that this formulation was safe to be administered subcutaneously. As the synthesized triblock has thermosensitive properties, and also has the hydrogen bonding between the N-methyl pyrrolidone molecules and PEG, therefore, these properties make ISFG formulation to have a smaller initial burst release compared to ISFI formulation.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
A 50% triblock NMP solution showed the best biocompatibility of all concentrations.
“Taking cellular toxicity into consideration, a 50% triblock NMP solution showed the best biocompatibility of all concentrations.”
From Levothyroxine: conventional and novel drug delivery formulations. (2023) · cites this paper as [278]
A 25 °C to 30 °C transition temperature from sol to gel limits the application of thermosensitive polymers in clinical practice.
“However, a 25 °C to 30 °C transition temperature from sol to gel limits the application of thermosensitive polymers in clinical practice.”
From Levothyroxine: conventional and novel drug delivery formulations. (2023) · cites this paper as [278]
In vitro experiments revealed a 500-hour gradual release of LT4 after a burst release of approximately 20% of the total contents in the first 24 hours for a thermosensitive polymer preparation.
“In vitro experiments revealed a 500-hour gradual release of LT4 after a burst release of ∼20% of the total contents in the first 24 hours.”
From Levothyroxine: conventional and novel drug delivery formulations. (2023) · cites this paper as [278]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
In situ-forming hydrogels--review of temperature-sensitive systems
Ruel-Gariépy, E., & Leroux, J.-C. (2004) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/j.ejpb.2004.03.019 · Cited by 1,297 · see citing works
Biodegradable block copolymers for delivery of proteins and water-insoluble drugs
Zentner, G. M., Rathi, R. C., Shih, C., McRea, J. C., Seo, M.-H., Oh, H., Rhee, B.-O., Mestecky, J. F., Moldoveanu, Z., Morgan, M. E., et al. (2001) · Journal of Controlled Release · doi:10.1016/s0168-3659(01)00276-0 · Cited by 587 · see citing works
Poly(lactic-co-glycolic) Acid-Controlled-Release Systems: Experimental and Modeling Insights
Hines, D. J., & Kaplan, D. L. (2013) · Critical Reviews in Therapeutic Drug Carrier Systems · doi:10.1615/critrevtherdrugcarriersyst.2013006475 · Cited by 399 · see citing works
Qiao, M., Chen, D., Xi-chen, M., & Liu, Y. (2005) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2005.01.017 · Cited by 277 · see citing works
Kaplan, G., Casoy, J., & Zummo, J. (2013) · Patient Preference and Adherence · doi:10.2147/ppa.s53795 · Cited by 201 · see citing works
Farahyar, S., Zaini, F., Kordbacheh, P., Rezaie, S., Safara, M., Raoofian, R., & Heidari, M. (2013) · DARU Journal of Pharmaceutical Sciences · doi:10.1186/2008-2231-21-1 · Cited by 125 · see citing works
Recent developments in microwave-assisted polymerization with a focus on ring-opening polymerization
Zhang, C., Liao, L., & Gong, S. (2007) · Green Chemistry · doi:10.1039/b608891k · Cited by 102 · see citing works
Pilon, D., Tandon, N., Lafeuille, M., Kamstra, R. L., Émond, B., Lefèbvre, P., & Joshi, K. (2017) · Clinical Therapeutics · doi:10.1016/j.clinthera.2017.08.008 · Cited by 98 · see citing works
Gong, C. Y., Shi, S., Dong, P. W., Yang, B., Qi, X., Guo, G. F., Gu, Y. C., Zhao, X., Wei, Y., & Qian, Z. Y. (2009) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.21780 · Cited by 93 · see citing works
Astaneh, R., Erfan, M., Moghimi, H., & Mobedi, H. (2008) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.21415 · Cited by 89 · see citing works
Tamboli, V., Mishra, G. P., & Mitra, A. K. (2013) · Colloid and Polymer Science · doi:10.1007/s00396-012-2854-0 · Cited by 87 · see citing works
In-situ forming PLGA implants for intraocular dexamethasone delivery
Bode, C., Kranz, H., Siepmann, F., et al. (2018) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2018.07.013 · Cited by 85 · see citing works
Tablet Splitting of a Narrow Therapeutic Index Drug: A Case with Levothyroxine Sodium
Shah, R. B., Collier, J. S., Sayeed, V. A., Bryant, A., Habib, M. J., & Khan, M. A. (2010) · AAPS PharmSciTech · doi:10.1208/s12249-010-9515-8 · Cited by 83 · see citing works
Ni, X., Cheng, A. H.-L., & Li, J. (2008) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.31906 · Cited by 81 · see citing works
Ahmed, T. A., Ibrahim, H. M., Samy, A. M., Kassem, A. A., Nutan, M. T. H., & Hussain, M. D. (2014) · AAPS PharmSciTech · doi:10.1208/s12249-014-0101-3 · Cited by 76 · see citing works
In Vitro Insulin Release from Thermosensitive Chitosan Hydrogel
Khodaverdi, E., Tafaghodi, M., Ganji, F., et al. (2012) · AAPS PharmSciTech · doi:10.1208/s12249-012-9764-9 · Cited by 75 · see citing works
Self-citationAval, S. F., Akbarzadeh, A., Yamchi, M. R., et al. (2014) · Artificial Cells Nanomedicine and Biotechnology · doi:10.3109/21691401.2014.934456 · Cited by 72 · see citing works
Thermoresponsive biodegradable PEG‐PCL‐PEG based injectable hydrogel for pulsatile insulin delivery
Payyappilly, S. S., Dhara, S., & Chattopadhyay, S. (2013) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.34800 · Cited by 70 · see citing works
Khodaverdi, E., Tekie, F. S. M., Mohajeri, S. A., et al. (2012) · AAPS PharmSciTech · doi:10.1208/s12249-012-9781-8 · Cited by 69 · see citing works
Self-citationGou, M., Gong, C., Zhang, J., Wang, X., Wang, X., Gu, Y., Guo, G. F., Chen, L., Luo, F., Zhao, X., et al. (2009) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.32546 · Cited by 66 · see citing works
Lü, Y., Wu, F., Duan, W., et al. (2019) · Materials Science and Engineering C · doi:10.1016/j.msec.2019.110294 · Cited by 66 · see citing works
Bakhshi, R., Vasheghani‐Farahani, E., Mobedi, H., et al. (2006) · Polymers for Advanced Technologies · doi:10.1002/pat.717 · Cited by 63 · see citing works
Roberge, C., Cros, J.-M., Serindoux, J., Cagnon, M.-E., Samuel, R., Vrlinič, T., Berto, P., Rech, A., Richard, J., & López‐Noriega, A. (2020) · Journal of Controlled Release · doi:10.1016/j.jconrel.2020.01.022 · Cited by 63 · see citing works
Cosolvent Effects on the Drug Release and Depot Swelling in Injectable In situ Depot-Forming Systems
Liu, H., & Venkatraman, S. S. (2012) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.23065 · Cited by 62 · see citing works
Guglielmi, R., Grimaldi, F., Negro, R., Frasoldati, A., Misischi, I., Graziano, F., Cipri, C., Guastamacchia, E., Triggiani, V., & Papini, E. (2018) · Endocrine, Metabolic & Immune Disorders - Drug Targets · doi:10.2174/1871530318666180125155348 · Cited by 57 · see citing works
Mechanistic analysis of PLGA/HPMC-based in-situ forming implants for periodontitis treatment
Do, M. P., Neut, C., Metz, H., et al. (2015) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/j.ejpb.2015.05.018 · Cited by 48 · see citing works
Dimer, F. A., Carvalho‐Wodarz, C. D. S., Goes, A., Cirnski, K., Herrmann, J. E., Schmitt, V., Pätzold, L., Abed, N., Rossi, C. D., Bischoff, M., et al. (2019) · Nanomedicine Nanotechnology Biology and Medicine · doi:10.1016/j.nano.2019.102125 · Cited by 47 · see citing works
Comparison of a laboratory and a production coating spray gun with respect to scale-up
Mueller, R., & Kleinebudde, P. (2007) · AAPS PharmSciTech · doi:10.1208/pt0801003 · Cited by 45 · see citing works
Current and New Approaches for Mucosal Vaccine Delivery
Rhee, J. H. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-811924-2.00019-5 · Cited by 44 · see citing works
Assessment of PLGA-PEG-PLGA Copolymer Hydrogel for Sustained Drug Delivery in the Ear
Feng, L., Ward, J. A., Li, S. K., et al. (2014) · Current Drug Delivery · doi:10.2174/1567201811666140118224616 · Cited by 39 · see citing works
Zare, M., Mobedi, H., Barzin, J., et al. (2007) · Journal of Applied Polymer Science · doi:10.1002/app.27520 · Cited by 36 · see citing works
Kamali, H., Khodaverdi, E., Hadizadeh, F., et al. (2018) · Journal of Drug Delivery Science and Technology · doi:10.1016/j.jddst.2018.06.027 · Cited by 34 · see citing works
Self-citationShah, H. S., Chaturvedi, K. K., Hamad, M. L., Bates, S., Hussain, A., & Morris, K. R. (2019) · AAPS PharmSciTech · doi:10.1208/s12249-018-1264-0 · Cited by 34 · see citing works
Lizambard, M., Menu, T., Fossart, M., Bassand, C., Agossa, K., Huck, O., Neut, C., & Siepmann, F. (2019) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2019.118833 · Cited by 34 · see citing works
In-vitro/In-vivo comparison of leuprolide acetate release from an in-situ forming plga system
Mashayekhi, R., Mobedi, H., Najafi, J., et al. (2013) · DARU Journal of Pharmaceutical Sciences · doi:10.1186/2008-2231-21-57 · Cited by 33 · see citing works
Tanguay, M., Girard, J., Scarsi, C., Mautone, G., & Larouche, R. (2019) · Clinical Pharmacology in Drug Development · doi:10.1002/cpdd.608 · Cited by 33 · see citing works
Kamali, H., Khodaverdi, E., Hadizadeh, F., et al. (2018) · Materials Science and Engineering C · doi:10.1016/j.msec.2018.11.058 · Cited by 33 · see citing works
Self-citationKoocheki, S., Madaeni, S. S., & Niroomandi, P. (2011) · Saudi Pharmaceutical Journal · doi:10.1016/j.jsps.2011.05.001 · Cited by 28 · see citing works
Astaneh, R., Moghimi, H., Erfan, M., et al. (2006) · DARU Journal of Pharmaceutical Sciences · Cited by 25 · see citing works
In-situ forming PLGA implants: How additives affect swelling and drug release
Bode, C., Kranz, H., Kruszka, A., Siepmann, F., & Siepmann, J. (2019) · Journal of Drug Delivery Science and Technology · doi:10.1016/j.jddst.2019.101180 · Cited by 25 · see citing works
Graves, R. A., Freeman, T., & Mandal, T. K. (2007) · AAPS PharmSciTech · doi:10.1208/pt0803062 · Cited by 24 · see citing works
Kamali, H., Khodaverdi, E., Hadizadeh, F., et al. (2019) · Journal of Drug Delivery Science and Technology · doi:10.1016/j.jddst.2019.01.011 · Cited by 23 · see citing works
Self-citationKhodaverdi, E., Akbari, A., Tekie, F. S. M., Mohajeri, S. A., Zohuri, G., & Hadizadeh, F. (2013) · PDA Journal of Pharmaceutical Science and Technology · doi:10.5731/pdajpst.2013.00908 · Cited by 21 · see citing works
Self-citationKhodaverdi, E., Rajabi, O., Farshid, F., et al. (2010) · doi:10.22038/ijbms.2010.5095 · Cited by 18 · see citing works
Self-citationEnvironmental photochemical fate and UVC degradation of sodium levothyroxine in aqueous medium
Parizi, M. P. S., Lastre-Acosta, A. M., Ishiki, H. M., Rossi, R. C., Mafra, R. C., & Teixeira, A. C. S. C. (2018) · Environmental Science and Pollution Research · doi:10.1007/s11356-018-2907-0 · Cited by 18 · see citing works
Ayoub, M. M., Jasti, B., Elantouny, N. G., El-Nahas, H. M., & Ghazy, F.-E. S. (2020) · Journal of Drug Delivery Science and Technology · doi:10.1016/j.jddst.2020.101585 · Cited by 18 · see citing works
Rahimi, M., Mobedi, H., & Behnamghader, A. (2015) · International Journal of Polymeric Materials · doi:10.1080/00914037.2015.1055633 · Cited by 15 · see citing works
Yehia, S. A., Halim, S. A. A., & Aziz, M. Y. (2018) · Current Drug Delivery · doi:10.2174/1567201815666180320101125 · Cited by 13 · see citing works
Sevelamer Carbonate Markedly Reduces Levothyroxine Absorption
Iovino, M., Iovine, N., Petrosino, A., Giagulli, V. A., Licchelli, B., Guastamacchia, E., & Triggiani, V. (2014) · Endocrine Metabolic & Immune Disorders - Drug Targets · doi:10.2174/1871530314666140902151804 · Cited by 11 · see citing works
Negro, R. (2018) · Endocrine Metabolic & Immune Disorders - Drug Targets · doi:10.2174/1871530318666180131103029 · Cited by 10 · see citing works
Leuprolide Acetate Release Study from γ-Irradiated PLGA-based In Situ Forming System
Shapourgan, M., Mobedi, H., Sheikh, N., et al. (2017) · Current Drug Delivery · doi:10.2174/1567201814666170329104047 · Cited by 7 · see citing works
Synthesis of PEG-PLGA copolymer for preparation of docetaxel nanoparticles
Yousefi, G., Tamaddon, A. M., & Parhizgar, E. (2012) · Research in Pharmaceutical Sciences · Cited by 3 · see citing works
Whitney, K. E., Ackerman, K., & Tenforde, A. (2020) · Elsevier eBooks · doi:10.1016/b978-0-323-67949-7.00015-x · Cited by 2 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Levothyroxine: conventional and novel drug delivery formulations.
Liu, H., Li, W., Zhang, W., Sun, S., & Chen, C. (2023) · Endocrine Reviews · doi:10.1210/endrev/bnac030 · Cited by 63 · see citing works
Poly(caprolactone)-based subcutaneous implant for sustained delivery of levothyroxine
Stewart, S. A., Domínguez-Robles, J., Utomo, E., Picco, C. J., Corduas, F., Mancuso, E., Amir, M. N., Bahar, M. A., Sumarheni, S., Donnelly, R. F., et al. (2021) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2021.121011 · Cited by 35 · see citing works
- Authors
- Kamali, H., Khodaverdi, E., Kaffash, E., Saffari, A. S., Shiadeh, S. N. R., Nokhodchi, A., & Hadizadeh, F.
- Affiliations
- Mashhad University of Medical Sciences (IR)
- University of Sussex (GB)
- Corresponding author
- Nokhodchi, Ali
- Hadizadeh, Farzin
- Venue
- Journal of Pharmaceutical Innovation
- Published
- 2020-08-11
- Volume
- 16
- Issue
- 4
- Pages
- 688-698
- ISSN
- 1872-5120 (ISSN-L)
- 1939-8042
- OpenAlex
- W3048673846
- Cited by
- 24
- References
- 53
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 3 · 2023: 1 · 2022: 10 · 2021: 4 · 2020: 1
- FWCI
- 1.55
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Journal of Pharmaceutical Innovation (publishedVersion, cc-by)
- Funders
- Mashhad University of Medical Sciences (N-961554)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
- Physical Sciences › Materials Science › Biomaterials › biodegradable polymer synthesis and properties
- Keywords
- levothyroxine, in situ gel, in situ forming implants, sustained drug release, burst release, ring-opening polymerization, thermoresponsive polymers, subcutaneous injection, cytotoxicity
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
