Sains Malaysiana 52(5)(2023): 1545-1556

http://doi.org/10.17576/jsm-2023-5205-16

Gel Mengandungi Nanozarah Kitosan yang Dimuatkan dengan DsiRNA dan Kurkumin sebagai Pembalut Luka Kencing Manis: Pelepasan Bahan Aktif dan Kesan Kesitotoksikan

(Gel Containing Chitosan Nanoparticles Loaded with DsiRNA and Curcumin as a Diabetic Wound Dressing: The Release of Active Ingredients and Cytotoxic Effects)

 FATIN HANANI MOHD FADHIL, NG SHIOW-FERN & HALIZA KATAS^*

Centre for Drug Delivery Technology, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300 Kuala Lumpur, Wilayah Persekutuan, Malaysia

Received:20 September 2022/Accepted: 14 April 2023

Abstrak

Baru-baru ini, RNA penghalang kecil substrat-Diser (DsiRNA) telah digabungkan dengan satu agen anti-radang semula jadi iaitu kurkumin (Cur) dalam bentuk nanozarah dan dimuatkan ke dalam gel untuk rawatan luka kencing manis. DsiRNA telah digunakan untuk melenyapkan ekspresi berlebihan gen pembawa prostaglandin (PGT) yang mengganggu respons pembentukan salur darah dan melambatkan penyembuhan luka. Selain sifat fizikokimia, keberkesanan dan keselamatan formulasi ini juga bergantung kepada corak pelepasan bahan aktif. Oleh itu,  kajian ini telah menilai corak pelepasan bahan aktif daripada nanozarah dan gel tersebut serta kesan kesitotoksikannya. Dalam kajian ini, kedua-dua bahan aktif ini telah dimasukkan ke dalam nanozarah kitosan (CSNPs) menggunakan kaedah gelasi ion dan kemudiannya dicampur ke dalam pembawa gel Pluronik F-127 (PF-127) pada kepekatan berbeza. CSNPs yang terhasil telah dioptimumkan untuk memperoleh zarah bersaiz kecil (301.3 ± 57.6 nm) dan cas permukaan yang tinggi (+23.7 ± 0.7 mV). Kebanyakan zarah adalah berbentuk sfera dengan keberkesanan pemerangkapan yang tinggi untuk Cur (86.8 ± 4.2%) dan DsiRNA (100.9 ± 52.5%). Gel yang terhasil pula mempunyai tekstur dan morfologi gel yang baik dan sesuai untuk aplikasi topikal. Kajian pelepasan dadah selama 24 jam secara in-vitro menunjukkan jumlah kumulatif pelepasan DsiRNA adalah lebih tinggi berbanding Cur iaitu dalam lingkungan 23.8-35.4 µg/cm². Kebolehidupan fibroblas yang didedahkan kepada formulasi ini juga adalah melebihi 80%, menggambarkan sifat tidak toksik CSNPs terhadap sel. Kesimpulannya, formulasi gel yang mengandungi CSNPSs ini berpotensi untuk dibangunkan sebagai pembalut luka dan agen penyembuh luka kencing manis.

Kata kunci: Diabetes; luka kronik; semi-pepejal; teknologi asid nukleik

Abstract

Recently, Dicer-substrate small interfering RNA (DsiRNA) has been incorporated into chitosan nanoparticles (CSNPs) in combination with a natural anti-inflammatory agent called curcumin (Cur) and later the nanoparticles were loaded into gels for treating diabetic wounds. DsiRNA is used to silence the overexpression of prostaglandin transporter gene (PGT) which attenuates blood vessel formation and slows the healing of diabetic wounds. In addition to physicochemical properties, the effectiveness and safety of these formulations depend on the release of active ingredients. Therefore, this study evaluated the release pattern of active ingredients from the nanoparticles and the gels as well as their cytotoxic effects. In this study, both active ingredients were incorporated into the CSNPs via ionic gelation method and loaded into different concentrations of Pluronic F-127 (PF-127) gels. The CSNPs were optimized to produce small-sized particles (301.3 ± 57.6 nm) and a high surface charge value (+23.7 ±0.7 mV). Most particles were spherical in shape with high percent of entrapment efficiency for Cur (86.8 ±4.2%) and DsiRNA (100.9 ±52.5%), respectively. The resulting gels had shown good texture and morphology that were suitable for topical applications. An in-vitro drug release study for 24 h showed that the cumulative amount of DsiRNA released was higher than Cur; in the range of 23.8-35.4 μg/cm². The viabilty of fibroblasts exposed to the formulations was more than 80%, showing the non-toxic property of CSNPs to cells. In conclusion, gels containing the CSNPSs have shown the potential to be developed as wound dressings and healing agents for diabetic wounds.

Keywords: Chronic wound; diabetes; nucleic acid technology; semi-solid

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^*Corresponding author; email: haliza.katas@ukm.edu.my