Microsponge-Based Gel Loaded with Immunosuppressant as a Simple and Valuable Strategy for Psoriasis Therapy: Determination of Pro-Inflammatory Response through Cytokine IL-2 mRNA Expression
Tacrolimus (TL) is a topical calcineurin inhibitor immunosuppressive drug widely used to manage various skin disorders. Herein, we report a TL-loaded microsphere gel formulation with severe atopic dermatitis effects that are required to manage skin disorders. The current study adopted a modified emu...
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| Format: | Article |
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MDPI AG
2023-11-01
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| Series: | Gels |
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| Online Access: | https://www.mdpi.com/2310-2861/9/11/871 |
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| author | Yasir Mehmood Hira Shahid Umar Inzamam ul Huq Hamza Rafeeq Hafiz Muhammad Bilal Khalid Mohammad N. Uddin Mohsin Kazi |
| author_facet | Yasir Mehmood Hira Shahid Umar Inzamam ul Huq Hamza Rafeeq Hafiz Muhammad Bilal Khalid Mohammad N. Uddin Mohsin Kazi |
| author_sort | Yasir Mehmood |
| collection | DOAJ |
| description | Tacrolimus (TL) is a topical calcineurin inhibitor immunosuppressive drug widely used to manage various skin disorders. Herein, we report a TL-loaded microsphere gel formulation with severe atopic dermatitis effects that are required to manage skin disorders. The current study adopted a modified emulsion solvent evaporation technique to synthesize TL-loaded microspheres, which were further converted into gels for skin use. Characterization of the synthesized formulation was performed by differential dynamic light scattering, scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, X-ray crystallography, Brunauer–Emmett–Teller (BET) analysis, differential scanning calorimetry, and drug release. A Franz diffusion cell was used to study the diffusion of TL for up to 8 h at pH 6.8 and 5.5. Evaluation of cell viability was determined by MTT assay and showed higher IC50 values compared to the plain drug. RNA extraction, real-time polymerase chain reaction (RT–PCR), and reverse transcription were also performed to determine the expression levels of the anti-inflammatory cytokine IL-2. Particle size determination was performed by a zeta sizer, and the TL microsphere size was 1745 ± 70 nm with a good polydispersity (0.337 ± 0.12). The drug entrapment efficiency was also very good at 60% ± 10, and the drug release was 93.9% ± 3.5 within 8 h. An in vitro diffusion study of the formulation also showed improved permeability at both pH values (4.5 and 5.5). The findings of the hemolytic tests demonstrated that TL-MG at concentrations of 50, 100, and 200 mg/mL did not produce any hemolysis. A dose-dependent pattern of cytotoxicity was found during the cell viability assay, with an IC50 value of 787.55 ± 12.78 µg/mL. There was a significant decrease in the IL-2 level in the TL-MG group compared to the other groups. TL-MG microspheres were nontoxic carriers for tacrolimus delivery, with greater loading capacity, a significant release profile, and enhanced cellular uptake with improved permeability. |
| first_indexed | 2024-03-09T16:48:35Z |
| format | Article |
| id | doaj.art-242a9de5e5a446209a06632cd638548c |
| institution | Directory Open Access Journal |
| issn | 2310-2861 |
| language | English |
| last_indexed | 2024-03-09T16:48:35Z |
| publishDate | 2023-11-01 |
| publisher | MDPI AG |
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| series | Gels |
| spelling | doaj.art-242a9de5e5a446209a06632cd638548c2023-11-24T14:43:20ZengMDPI AGGels2310-28612023-11-0191187110.3390/gels9110871Microsponge-Based Gel Loaded with Immunosuppressant as a Simple and Valuable Strategy for Psoriasis Therapy: Determination of Pro-Inflammatory Response through Cytokine IL-2 mRNA ExpressionYasir Mehmood0Hira Shahid1Umar Inzamam ul Huq2Hamza Rafeeq3Hafiz Muhammad Bilal Khalid4Mohammad N. Uddin5Mohsin Kazi6Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Government College University Faisalabad, Faisalabad P.O. Box 38000, PakistanDepartment of Pharmacology, Faculty of Pharmaceutical Sciences, Government College University Faisalabad, Faisalabad P.O. Box 38000, PakistanLahore College of Pharmaceutical Sciences, Lahore P.O. Box 54000, PakistanDepartment of Biochemistry, Riphah International University, Faisalabad Campus, Faisalabad P.O. Box 38000, PakistanDepartment of Pharmaceutics, Faculty of Pharmaceutical Sciences, Government College University Faisalabad, Faisalabad P.O. Box 38000, PakistanCollege of Pharmacy, Mercer University, 3001 Mercer University Drive, Atlanta, GA 30341, USADepartment of Pharmaceutics, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi ArabiaTacrolimus (TL) is a topical calcineurin inhibitor immunosuppressive drug widely used to manage various skin disorders. Herein, we report a TL-loaded microsphere gel formulation with severe atopic dermatitis effects that are required to manage skin disorders. The current study adopted a modified emulsion solvent evaporation technique to synthesize TL-loaded microspheres, which were further converted into gels for skin use. Characterization of the synthesized formulation was performed by differential dynamic light scattering, scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, X-ray crystallography, Brunauer–Emmett–Teller (BET) analysis, differential scanning calorimetry, and drug release. A Franz diffusion cell was used to study the diffusion of TL for up to 8 h at pH 6.8 and 5.5. Evaluation of cell viability was determined by MTT assay and showed higher IC50 values compared to the plain drug. RNA extraction, real-time polymerase chain reaction (RT–PCR), and reverse transcription were also performed to determine the expression levels of the anti-inflammatory cytokine IL-2. Particle size determination was performed by a zeta sizer, and the TL microsphere size was 1745 ± 70 nm with a good polydispersity (0.337 ± 0.12). The drug entrapment efficiency was also very good at 60% ± 10, and the drug release was 93.9% ± 3.5 within 8 h. An in vitro diffusion study of the formulation also showed improved permeability at both pH values (4.5 and 5.5). The findings of the hemolytic tests demonstrated that TL-MG at concentrations of 50, 100, and 200 mg/mL did not produce any hemolysis. A dose-dependent pattern of cytotoxicity was found during the cell viability assay, with an IC50 value of 787.55 ± 12.78 µg/mL. There was a significant decrease in the IL-2 level in the TL-MG group compared to the other groups. TL-MG microspheres were nontoxic carriers for tacrolimus delivery, with greater loading capacity, a significant release profile, and enhanced cellular uptake with improved permeability.https://www.mdpi.com/2310-2861/9/11/871tacrolimusmicroparticlesdrug deliverypermeabilitypsoriasis therapy |
| spellingShingle | Yasir Mehmood Hira Shahid Umar Inzamam ul Huq Hamza Rafeeq Hafiz Muhammad Bilal Khalid Mohammad N. Uddin Mohsin Kazi Microsponge-Based Gel Loaded with Immunosuppressant as a Simple and Valuable Strategy for Psoriasis Therapy: Determination of Pro-Inflammatory Response through Cytokine IL-2 mRNA Expression Gels tacrolimus microparticles drug delivery permeability psoriasis therapy |
| title | Microsponge-Based Gel Loaded with Immunosuppressant as a Simple and Valuable Strategy for Psoriasis Therapy: Determination of Pro-Inflammatory Response through Cytokine IL-2 mRNA Expression |
| title_full | Microsponge-Based Gel Loaded with Immunosuppressant as a Simple and Valuable Strategy for Psoriasis Therapy: Determination of Pro-Inflammatory Response through Cytokine IL-2 mRNA Expression |
| title_fullStr | Microsponge-Based Gel Loaded with Immunosuppressant as a Simple and Valuable Strategy for Psoriasis Therapy: Determination of Pro-Inflammatory Response through Cytokine IL-2 mRNA Expression |
| title_full_unstemmed | Microsponge-Based Gel Loaded with Immunosuppressant as a Simple and Valuable Strategy for Psoriasis Therapy: Determination of Pro-Inflammatory Response through Cytokine IL-2 mRNA Expression |
| title_short | Microsponge-Based Gel Loaded with Immunosuppressant as a Simple and Valuable Strategy for Psoriasis Therapy: Determination of Pro-Inflammatory Response through Cytokine IL-2 mRNA Expression |
| title_sort | microsponge based gel loaded with immunosuppressant as a simple and valuable strategy for psoriasis therapy determination of pro inflammatory response through cytokine il 2 mrna expression |
| topic | tacrolimus microparticles drug delivery permeability psoriasis therapy |
| url | https://www.mdpi.com/2310-2861/9/11/871 |
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