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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 SIDDIQUE4,*
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
Diserahkan: 2 Oktober 2023/Diterima: 2 Januari 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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*Pengarang untuk surat-menyurat; email: muhammad.siddique@nbu.edu.sa
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