Sains Malaysiana 53(1)(2024): 201-215

http://doi.org/10.17576/jsm-2024-5301-16

Stability and Safety Analysis of Statin-Loaded Nano-films for the Treatment of Diabetic Wound

(Analisis Kestabilan dan Keselamatan Filem Nano Sarat Statin untuk Rawatan Luka Diabetes)

MARIA RASOOL¹, NAWAF M. ALOTAIBI², MUHAMMAD SARFRAZ³ & MUHAMMAD IRFAN SIDDIQUE^4,*

¹Institute of Pharmaceutical Sciences, Faculty of Biosciences, University of Veterinary and Animal Sciences, Lahore

²Department of clinical Pharmacy, Faculty of Pharmacy, Northern Border University, Rafha, Saudi Arabia

³College of Pharmacy, Al Ain University, Al Ain, postal code 64141. UAE

⁴Department of Pharmaceutical Sciences, Faculty of Pharmacy, Northern Border University, Rafha, Saudi Arabia

Received: 2 October 2023/Accepted: 2 January 2024

Abstract

Diabetes mellitus (DM) is a metabolic disease that delays the regular stages of the wound's healing process due to delayed inflammatory stages. Due to foot pressure points, chronic foot wounds are ultimately considered the primary cause of lower leg amputation. Diabetic patients have vascular dysfunction and neuropathy, leading to inadequate oxygen supply to the wound area. Statins have a crucial role in the regulation of angiogenesis that could increase vascular endothelial growth factor (VEGF) synthesis. By offering a localized treatment approach while minimizing systemic side effects associated with oral medication, this study aimed to develop statin-loaded nanofilms to determine their stability and safety among healthy individuals as a potential procedure for diabetic wound healing. Simvastatin (SIM) loaded nanofilms formulations (F1-F10) were prepared using the solvent casting method. The formulation was optimized based on tests such as physical appearance, tensile strength, microscopic photographs, morphology, and drug content uniformity. ICH guidelines were followed to determine various parameters (physical appearances, tensile strength, microscopic photographs, morphology, and drug content uniformity) for six-month stability study at three different storage conditions. Safety analysis of the nanofilms was performed on healthy human skin using the Draize skin irritation test. Results showed F7 formulation was considered an optimized formulation as well as stable through the storage period at 4 ± 2°C, 25 ± 2°C, and 40 ± 2 °C. Furthermore, Primary Irritation Index results (PII was 0 showed no irritation in case and control groups) indicate its safety and biocompatibility to skin. Thus, the optimized statin-loaded nanofilm is stable, safe, and non-toxic, which may be used as a potential diabetic wound healing agent.

Keywords: Nanoparticles; polymeric drug carrier; safety analysis; targeted drug delivery; wound healing

Abstrak

Diabetes mellitus (DM) adalah penyakit metabolik yang melambatkan peringkat biasa proses penyembuhan luka disebabkan oleh tahap keradangan yang tertangguh. Disebabkan oleh titik tekanan kaki, luka kaki kronik akhirnya dianggap sebagai punca utama amputasi kaki bawah. Pesakit diabetes mempunyai disfungsi vaskular dan neuropati yang membawa kepada bekalan oksigen yang tidak mencukupi ke kawasan luka. Statin mempunyai peranan penting dalam pengawalan angiogenesis yang boleh meningkatkan sintesis faktor pertumbuhan endotelium vaskular (VEGF). Dengan menawarkan pendekatan rawatan setempat sambil meminimumkan kesan sampingan sistemik yang berkaitan dengan ubat oral, kajian ini bertujuan untuk membangunkan nanofilem yang dimuatkan statin untuk menentukan kestabilan dan keselamatan mereka dalam kalangan individu yang sihat sebagai prosedur yang berpotensi untuk penyembuhan luka diabetes. Formulasi nanofilem yang dimuatkan simvastatin (SIM) (F1-F10) telah disediakan menggunakan kaedah tuangan pelarut. Formulasi dioptimumkan berdasarkan ujian seperti penampilan fizikal, kekuatan tegangan, gambar mikroskopik, morfologi dan keseragaman kandungan ubat. Garis panduan ICH diikuti untuk menentukan pelbagai parameter (penampilan fizikal, kekuatan tegangan, gambar mikroskopik, morfologi, dan keseragaman kandungan ubat) untuk kajian kestabilan enam bulan pada tiga keadaan penyimpanan yang berbeza. Analisis keselamatan nanofilem telah dilakukan pada kulit manusia yang sihat menggunakan ujian kerengsaan kulit Draize. Keputusan menunjukkan formulasi F7 dianggap sebagai rumusan yang dioptimumkan serta stabil melalui tempoh penyimpanan pada 4 ± 2 °C, 25 ± 2 °C dan 40 ± 2 °C. Tambahan pula, keputusan Indeks Kerengsaan Utama (PII ialah 0 menunjukkan tiada kerengsaan dalam kes dan kumpulan kawalan) menunjukkan keselamatan dan biokeserasiannya kepada kulit. Oleh itu, nanofilem dimuatkan statin yang dioptimumkan adalah stabil, selamat dan tidak toksik yang boleh digunakan sebagai agen penyembuhan luka diabetes yang berpotensi.

Kata kunci: Analisis keselamatan; nanozarah; pembawa dadah polimer; penghantaran dadah yang disasarkan; penyembuhan luka

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*Corresponding author; email: muhammad.siddique@nbu.edu.sa