Tamoxifen Citrate-Loaded γ-Cyclodextrin Metal Organic Frameworks: Studies on permeability through Caco-2 cell monolayers

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Mutlu Ağardan N. B., Edisan Ş., Gülsün İnal T.

21st International Pharmaceutical Technology Symposium, Ankara, Türkiye, 9 - 11 Eylül 2024, ss.184-185

  • Yayın Türü: Bildiri / Özet Bildiri
  • Basıldığı Şehir: Ankara
  • Basıldığı Ülke: Türkiye
  • Sayfa Sayıları: ss.184-185
  • Gazi Üniversitesi Adresli: Evet

Özet

Tamoxifen Citrate-Loaded γ-Cyclodextrin Metal Organic Frameworks: Studies on permeability through Caco-2 cell monolayers

N.Başaran Mutlu-Ağardan1; Şeyma Edisan1; Tuğba Gülsün İnal2

1 Gazi University, Department of Pharmaceutical Technology, Ankara, Turkey

2 Hacettepe University, Department of Pharmaceutical Technology, Ankara, Turkey

Correspondence: bmutlu@gazi.edu.tr


INTRODUCTION

Tamoxifen citrate (TMX) is a BCS class II drug which is used orally in the treatment of estrogen positive breast cancers [1]. CD-MOFs offer a practical, new platform to obtain micro-and nano-sized drug delivery systems to provide controlled release, increased solubility and bioavailability [2]. In this study, the permeability enhancing efficacy of γ-CD-MOFs was investigated using Caco-2 cells, on behalf of TMX.

 

Materials and Methods

Materials

γ-Cyclodextrin was donated by Cyclolab Ltd. TMX was a kind gift of Deva Holding. All the materials for cell culture studies were of cell culture grade.

Method

γ-CD-MOFs were obtained by two methods based on modified methanol diffusion method. TMX was encapsulated into presynthesized γ-CD-MOFs via impregnation method. TMX-γ-CD-MOFs were fully characterized by DSC, XRD, FT-IR and BET studies. Then, TMX-γ-CD-MOFs were evaluated in terms of cytotoxicity, and the effect of the formulation on the transport of TMX from Caco-2 cells. Caco-2 cell transport studies were conducted for 2 hours and the samples were analyzed by HPLC for TMX content.

Results and Discussion

The formulations prepared by two methods were named TMX-CD-MOF-1 and TMX-CD-MOF-2. The formation of γ-CD-MOFs and TMX loading to γ-CD-MOFs were confirmed by detailed characterization studies. The particle size of formulations increased approximately 1.8 times due to TMX loading. Cytotoxicity studies were performed on Caco-2 cells to determine the TMX concentration to be used in permeability studies increasing concentrations. γ-CD-MOFs did not presented cytotoxicity on Caco-2 cells even at high concentrations and TMX concentration was determined as 100 µg/mL to obtain cell viability over 80% (Figure 1). Formulations successfully increased oral permeability of pure TMX (Figure 2).

metin, çizgi, yazı tipi, ekran görüntüsü içeren bir resim Açıklama otomatik olarak oluşturuldu

Figure 1. Cell viability results of TMX, TMX/γ-CD physical mixture, and TMX-ɣ-CD-MOFs

metin, diyagram, ekran görüntüsü, yazı tipi içeren bir resim Açıklama otomatik olarak oluşturuldu

Figure 2. Comparative graph of apparent permeability coefficients calculated as a result of permeability studies from Caco-2 cells.

According to the results of the Caco-2 cell permeability study, TMX-γ-CD-MOF-1 increased the apparent permeability by 2.24 fold, while TMX-γ-CD-MOF-2 increased it by 3.57 fold compared to pure TMX and TMX/ γ-CD physical mixture.

CONCLuSION

γ-CD-MOFs could be a feasible and promising approach to enhance permeability properties of low soluble/permeable drugs with ease of scale-up and manufacturing.

References

1.      Ravikumar, N.R., Bharadwaj, M.,& Madhusudhan, B (2016). Tamoxifen citrate-loaded poly(d,l) lactic acid nanoparticles: Evaluation for their anticancer activity in vitro and in vivo. J Biomater Appl, 31(5), 755-772.

2.      Aiassa, V., Garnero, C., Longhi, M. R., & Zoppi,A.(2021). Cyclodextrin Multicomponent Complexes: Pharmaceutical Applications. Pharmaceutics, 13(7).

 

Acknowledgment

This study was supported by a grant from TÜBİTAK (SBAG-222S923). Thanks to TÜBİTAK