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. 2024 Jul 15;17(14):3510.
doi: 10.3390/ma17143510.

Novel Collagen Membrane Formulations with Irinotecan or Minocycline for Potential Application in Brain Cancer

Andreea-Anamaria Idu  1   2 , Mădălina Georgiana Albu Kaya  3 , Ileana Rău  1 , Nicoleta Radu  4   5 , Cristina-Elena Dinu-Pîrvu  6   7 , Mihaela Violeta Ghica  6   7
Affiliations

Novel Collagen Membrane Formulations with Irinotecan or Minocycline for Potential Application in Brain Cancer

Andreea-Anamaria Idu et al. Materials (Basel). .

Abstract

Our study explores the development of collagen membranes with integrated minocycline or irinotecan, targeting applications in tissue engineering and drug delivery systems. Type I collagen, extracted from bovine skin using advanced fibril-forming technology, was crosslinked with glutaraldehyde to create membranes. These membranes incorporated minocycline, an antibiotic, or irinotecan, a chemotherapeutic agent, in various concentrations. The membranes, varying in drug concentration, were studied by water absorption and enzymatic degradation tests, demonstrating a degree of permeability. We emphasize the advantages of local drug delivery for treating high-grade gliomas, highlighting the targeted approach's efficacy in reducing systemic adverse effects and enhancing drug bioavailability at the tumor site. The utilization of collagen membranes is proposed as a viable method for local drug delivery. Irinotecan's mechanism, a topoisomerase I inhibitor, and minocycline's broad antibacterial spectrum and inhibition of glial cell-induced membrane degradation are discussed. We critically examine the challenges posed by the systemic administration of chemotherapeutic agents, mainly due to the blood-brain barrier's restrictive nature, advocating for local delivery methods as a more effective alternative for glioblastoma treatment. These local delivery strategies, including collagen membranes, are posited as significant advancements in enhancing therapeutic outcomes for glioblastoma patients.

Keywords: bioengineering; collagen-based membranes; glioblastoma; irinotecan; minocycline; nanotechnology.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 6
Figure 6
Antibacterial effects of minocycline. (a) Test performed on thin biofilm; (b) minimal inhibitory concentration of minocycline on S. aureus, for different applied standards (data adapted after Bidell et al., 2021 [44]); (c) effect of minocycline 5 mg/mL on E. coli; (d) effect of thin film M1 on E. coli; (e) effect of minocycline 5 mg/mL on S. aureus; (f) effect of thin film M1 on S. aureus; (g) effect of thin film IR4 with irinotecan on E. coli; (h) effect of thin film IR3 with irinotecan on E. coli; (i) effect of thin film IR1 with irinotecan on E. coli. n.d. = not determined; CLSI = Clinical and Laboratory Standard Institute; EUCAST = European Committee on Antimicrobial Susceptibility; FDA = Food and Drug Administration, USA.
Figure 1
Figure 1
Collagen membranes with minocycline 40% (a) and irinotecan 10% (b).
Figure 2
Figure 2
Water absorption for collagen membranes with different concentrations of minocycline. A p-value > 0.5 indicates that the results obtained are not statistically significant. “*” corresponds to results with statistical significance (0.5 < p < 0.1), “**” corresponds to distinctly statistically significant results (0.1 ≤ p < 0.01), and “***” corresponds to highly statistically significant results (p ≤ 0.01).
Figure 3
Figure 3
Water absorption for the collagen-based membranes with different irinotecan concentrations. A p-value > 0.5 indicates that the results obtained are not statistically significant. “*” corresponds to results with statistical significance (0.5 < p < 0.1), “**” corresponds to distinctly statistically significant results (0.1 ≤ p < 0.01), and “***” corresponds to highly statistically significant results (p ≤ 0.01).
Figure 4
Figure 4
Collagenase degradation of collagen membranes with minocycline. A p-value > 0.5 indicates that the results obtained are not statistically significant. “*” corresponds to results with statistical significance (0.5 < p < 0.1), “**” corresponds to distinctly statistically significant results (0.1 ≤ p < 0.01), and “***” corresponds to highly statistically significant results (p ≤ 0.01).
Figure 5
Figure 5
Collagenase degradation of the collagen membranes with irinotecan. A p-value > 0.5 indicates that the results obtained are not statistically significant. “*” corresponds to results with statistical significance (0.5 < p < 0.1), “**” corresponds to distinctly statistically significant results (0.1 ≤ p < 0.01), and “***” corresponds to highly statistically significant results (p ≤ 0.01).
Figure 7
Figure 7
Time-dependent cumulative release patterns of minocycline from collagen membranes.
Figure 8
Figure 8
Time-dependent cumulative release patterns of irinotecan from collagen membranes.
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