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. 2026 Jan 2;12(1):51.
doi: 10.3390/gels12010051.

Rectal In Situ Thermosensitive Gel Loaded with Agomelatine-Silver Nanoparticles: Formulation and Characterization

Marwa H Abdallah  1 , Mohamed S Mohamed  2 , Tamer M Shehata  3 , Wael A Abdelhafez  2 , Mahmoud M A Elsayed  4 , Abd El Hakim Ramadan  5 , Islam Kamal  5 , Abdulsalam M Kassem  6   7 , Mahmoud Elkot Mostafa  8 , Ayman Salama  9 , Reda A Mahmoud  2 , Ahmed A El-Shenawy  2   10   11
Affiliations

Rectal In Situ Thermosensitive Gel Loaded with Agomelatine-Silver Nanoparticles: Formulation and Characterization

Marwa H Abdallah et al. Gels. .

Abstract

Agomelatine (AG) is a novel antidepressant characterized by distinct mechanism of action and minimal side effects. However, extensive first-pass hepatic metabolism limits its clinical efficacy after oral administration, leading to low bioavailability (<5%). To get around these restrictions, the current study set out to create and assess a rectal thermosensitive in situ gel using biosynthesized AG-silver nanoparticles (AG-AgNPs). AG-AgNPs were successfully synthesized with gum acacia as a stabilizing agent, using silver nitrate as a precursor, and ascorbic acid as a reducing agent. The in situ gel formulation was optimized using a 32 factorial design, and then physicochemical, in vitro, and in vivo assessments were conducted. Nanoparticle formation was also evidenced by the appearance of a visible color change, UV-VIS, TEM, and XRD analysis techniques, which depicted spherical-shaped nanoparticles and a crystalline nature. The formulated optimized thermosensitive in situ gel showed good properties, which included drug content of 91.64%, gelation temperature of 26.63 °C, pH of 7.2, gel strength of 36.98 s, and sustained drug release of 80.24% in 6 h. The relative bioavailability in animal studies showed a remarkable increase in systemic availability with 277.5% relative bioavailability in comparison to an oral tablet formulation. In summary, results show that the AG-AgNP-loaded thermosensitive in situ gel could have potential use as a rectal delivery drug for bypassing first-pass effects and improving bioavailability for the drug Agomelatine.

Keywords: agomelatine; enhanced bioavailability; green biosynthesis; rectal drug delivery; silver nanoparticles; sustained release; thermosensitive gel.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
(A) UV Spectrophotometry of AgNPs at different time intervals, (B) before addition of silver nitrate, and (C) after addition of silver nitrate (2 h).
Figure 2
Figure 2
TEM image of AgNPs synthesized with 0.5%, w/v gum acacia and 1 mM silver nitrate.
Figure 3
Figure 3
(A) Particle size and (B) Zeta potential of the synthesized AG-loaded AgNPs.
Figure 4
Figure 4
X-ray diffraction pattern of the synthesized AG-loaded with AgNPs.
Figure 5
Figure 5
FTIR spectra of pure agomelatine, unprocessed silver nitrate, gum acacia, ascorbic acid, and the prepared silver nanoparticles.
Figure 6
Figure 6
Three-dimensional response surface plots estimating the effect of independent variables on the gelation temperature, the gel strength, and the cumulative % AG released after 6 h.
Figure 7
Figure 7
Contour plots estimating the effect of independent variables on the GT, the GS, and the cumulative % AG released after 6 h.
Figure 8
Figure 8
In vitro release profile of AG from various rectal in situ gel formulations (data expressed as the mean ± SD, n = 3). The various formulations are coded with F1, F2, F3, … and F9.
Figure 9
Figure 9
Composition and the dependent variables of the optimized rectal in situ gel formulation.
Figure 10
Figure 10
Histopathology photomicrographs of (A) untreated rectal mucosa and (B) rectal mucosa treated with optimized in situ gel formula.
Figure 11
Figure 11
The rabbit plasma concentration-time curve after a single-dose administration of different agomelatine dosage forms (The results are expressed as the mean ± SD, n = 3).
See this image and copyright information in PMC

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