Ketoconazole-pamam Dendrimer Supramolecular Complex for Prolonged Delivery by In Vitro and In Vivo Studies

Irina  KACSO; Ioana  BÂLDEA; Maria-Olimpia  MICLĂUȘ; Augustin Cătalin MOŢ; Remus  MOLDOVAN; Flavia  MARTIN

doi:10.24193/subbchem.2023.4.10

Ketoconazole-pamam Dendrimer Supramolecular Complex for Prolonged Delivery by In Vitro and In Vivo Studies

Authors

Irina KACSO National Institute for Research and Development of Isotopic and Molecular Technologies, Cluj-Napoca, Romania. Corresponding author: flavia.martin@itim-cj.ro. https://orcid.org/0000-0003-1039-0543
Ioana BÂLDEA Department of Physiology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania. Email: ioana.baldea@umfcluj.ro. https://orcid.org/0000-0003-4046-7310
Maria-Olimpia MICLĂUȘ National Institute for Research and Development of Isotopic and Molecular Technologies, Cluj-Napoca, Romania. Email: maria.miclaus@itim-cj.ro. https://orcid.org/0000-0002-9738-2417
Augustin Cătalin MOŢ Faculty of Chemistry and Chemical Engineering, Babes-Bolyai University, Cluj-Napoca, Romania. Email: augustin.mot@ubbcluj.ro. https://orcid.org/0000-0002-1679-0487
Remus MOLDOVAN Department of Physiology, "Iuliu Haţieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania. Email: remus_ri@yahoo.com. https://orcid.org/0000-0002-4441-7030
Flavia MARTIN National Institute for Research and Development of Isotopic and Molecular Technologies, Cluj-Napoca, Romania. Email: flavia.martin@itim-cj.ro.

DOI:

https://doi.org/10.24193/subbchem.2023.4.10

Keywords:

Ketoconazole, PAMAM dendrimer, Drug-dendrimer complex, Solubility, Cell viability, Mouse ear sensitization test

Abstract

The current study investigates the potential of the supramolecular complex between the antifungal agent Ketoconazole (KTZ) and PAMAM dendrimer G5 generation to be used as a topically applied antimycotic drug. The new drug-dendrimer formulation was confirmed by combining XRPD, FT-IR and DSC analytical techniques, and presents improved aqueous solubility and delayed in vitro release profile compare to pure KTZ. The biological assays data showed the biocompatibility of the supramolecular complex and improved delivery of the encapsulated KTZ into the superficial layers of skin and mucosa at the mycotic infections site, leading to a better outcome of the infection.

References

A. H. Groll; J. Lumb; Future Microbiol., 2012, 7, 179-184

D. T. Mlynarczyk; J. Dlugaszewska; A. Kaluzna-Mlynarczyk; T. Goslinski; JCR, 2021, 330, 599-617

G. L. Amidon; H. Lennernäs; V. P. Shah; J. R. Crison; Pharm Res., 1995, 12(3), 413-420

S. Basa; T. Muniyappan; P. Karatgi; R. Prabhu; R. Pillai; Drug. Dev. Ind. Pharm., 2008, 34, 1209-1218

E. N. Lo; L. A. Beckett; C. -X. Pan; D. Robles; J. M. Suga; J. M. Sands; P. N. Lara; Prostate. Cancer. Prostatic. Dis., 2015, 18, 144-148

European Medicines Agency. Ketoconazole HRA; http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/003906/human_med_001814.jsp&mid=WC0b01ac058001d124.

F. D. Choi; M. L. W. Juhasz; N. A. Mesinkovska; J. Dermatolog. Treat., 2019, 30(8), 760-771

F. A. Martin; M. M. Pop; G. Borodi; X. Filip; I. Kacso; Cryst. Growth. Des., 2013, 13(10), 4295-4304

I. Kacso; L. M. Rus; F. Martin; M. Miclaus; X. Filip, M. Dan; J. Therm. Anal. Calorim., 2021, 143, 3499-3506

F. Martin; M. Pop; I. Kacso; I. G. Grosu; M. Miclăuş; D. Vodnar; I. Lung; G. A. Filip; E. D. Olteanu; R. Moldovan; A. Nagy; X. Filip; I. Bâldea; Molec. Pharmaceutics, 2020, 17(3), 919-932

X. Chen; D. Li; Z. Deng; H. Zhang; Cryst. Growth Des., 2020, 20, 6973-6982

A. K. Aggarwal; S. Jain; Chem. Pharm. Bull., 2011, 59, 629-638

P. K. Mididoddi; M. A. Repka; Eur. J. Pharm. Biopharm., 2007, 66, 95-105

J. Taraszewska; M. J. Kozbial; Inclusion Phenom. Mol. Recognit. Chem., 2005, 53, 155-161

A.S. Chauhan; Molecules, 2018, 23(4), 938-947

A. Santos; F. Veiga; A. Figueiras; Materials, 2020, 13(65), 1-31

V. Patel; P. Patel; J. V. Patel; P. M. Patel; J. Indian Chem. Society, 2022, 99(7), 100516

N. P. Silva JR; F. P. Menacho; M. Chorilli; J. Pharma., 2012, 2, 23-30

R.V. de Araújo; S. da Silva Santos; F. E. Igne; J. Giarolla; Molecules, 2018, 23, 2849-2876

K. Winnicka; M. Wroblewska; P. Wieczorek; P.T. Sacha; E. Tryniszewska; Molecules, 2012, 17, 4612-4624

J. Jose; R. N. Charyulu; Optoelectronics and advanced materials – Rapid Communications, 2016, 10(7-8), 604–608

A. Chauhana; B. Antona; M. K. Singh; Dendrimers for drug solubilization, dissolution and bioavailability, in Pharmaceutical Applications of Dendrimers, A. Chauhan, H. Kulhari Eds.; Elsevier, 2019, Chapter 3, pp. 59-92

B. Yavuz; S. B. Pehlivan; N. Unlu; Sci. World J., 2013, 732340

S. Svenson; Chem. Soc. Rev., 2015, 44(12), 4131-44

P. Papneja; M. Kumar Kataria; A. Bilandi; EJPMR, 2015, 2(5), 990-1014

A. Karolewicz; A. Górniak; E. Owczarek; A. Żurawska-Plaksej; J. Pluta Piwowar; J. Therm. Anal. Calorim., 2014, 115, 2487-2493

S. Uppuluri; P. R. Dvornic; J. W. Klimash; P. I. Carver; N. C. Beck Tan; The Properties of Dendritic Polymers I: Generation 5 Poly(amidoamine) Dendrimers, 2022

C. D. Bevan; R. S. Lloyd; Anal. Chem., 2000, 72(8), 1781-1787

S. D’Souza; Advances in Pharmaceutics, 2014, Art. ID 304757, 1-12

J. Jose; R. N. Charyulu; Int. J. Pharm. Investig., 2016, 6(2), 123-127

J. ‐L. Garrigue; J. ‐F. Nicolas; R. Fraginals; C. Benezra; H. Bour; D. Schmitt; Contact Dermatitis., 1994, 30(4), 231-237

P. S. Thorne; C. Hawk; S. D. Kaliszewski; P. D. Guiney; Fundam. Appl. Tox., 1991, 17, 807-820

C. G. Shayne; J. D. Brendan; D. W. Dobbs, C. Reilly, R. D.Walsh, Toxicol and Applied Pharmacol, 1986, 84:(1), 93-114

L. Tordesillas; R. Goswami; S. Benedé; G. Grishina; D. Dunkin; K. M. Järvinen; S. J. Maleki; H. A. Sampson; M. C. Berin; J. Clin. Invest. 2014, 124(11), 4965-7

S. Danescu; G. A. Filip; R. Moldovan; D. Olteanu; A. Nagy; X. Filip; F. Martin; I. Kacso; I. Baldea; Inflammopharmacology, 2021, 29(3), 721-733.

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Published

2023-12-20

How to Cite

KACSO, I. ., BÂLDEA, I. ., MICLĂUȘ, M.-O. ., MOŢ, A. C., MOLDOVAN, R. ., & MARTIN, F. . (2023). Ketoconazole-pamam Dendrimer Supramolecular Complex for Prolonged Delivery by In Vitro and In Vivo Studies. Studia Universitatis Babeș-Bolyai Chemia, 68(4), 137–154. https://doi.org/10.24193/subbchem.2023.4.10