Sains Malaysiana 53(6)(2024): 1343-1362

http://doi.org/10.17576/jsm-2024-5306-10

Design and Characterisation of Curcumin-Loaded Nanostructured Lipid Carriers for Safe and Efficient Topical Drug Delivery in The Treatment of Pressure Ulcer

(Reka Bentuk dan Pencirian Pembawa Lipid Berstruktur Nano Berpengisi Kurkumin untuk Penghantaran Ubat Topikal yang Selamat dan Berkesan dalam Rawatan Ulser Tekanan)

NUR AMIRA MOHD SHAMSUDDIN¹, FAZREN AZMI¹, KHAIRANA HUSAIN², LEONG LEK MUN³ & MOHD HANIF ZULFAKAR¹,*

¹Centre for Drug Delivery Technology & Vaccine, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, 50300 Kuala Lumpur, Malaysia

²Centre for Drug and Herbal Development, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, 50300 Kuala Lumpur, Malaysia

³Prima Nexus Sdn. Bhd., 28-1B, Jalan Puteri 1/2, Bandar Puteri, 47100 Puchong, Selangor, Malaysia

Diserahkan: 14 Februari 2024/Diterima: 16 Mei 2024

Abstract

Pressure ulcers (PU) are chronic lesions with a high prevalence in at-risk populations. Although curcumin has various therapeutic properties, its use as a dermal therapeutic agent is limited by its poor solubility and permeability. This study aimed to develop nanostructured lipid carriers (NLCs) to facilitate the topical use of curcumin as wound healing agent in treating PU. The optimised curcumin-NLCs were characterised for their physicochemical properties, drug release, and skin permeation, while effectiveness and toxicity were investigated via cell viability, scratch assays, and an in vivo skin irritation test. The optimised curcumin-NLCs comprised 3.5% solid lipids, 1% surfactant, and 2% co-surfactant with an average particle size of 134.68±6.0 nm, polydispersity index of 0.248±0.00, zeta potential of −44.94±5.44, percentage of encapsulation efficiency of 93.42±0.32%, and drug loading of 0.11±0.00%. Curcumin-NLCs showed stable physicochemical properties and extended drug release for up to 48 h, with a cumulative release of 77.72% following a first-order kinetics. The formulation exhibited slower curcumin permeation than the free curcumin. Furthermore, the safe and non-toxic curcumin-NLCs were highly effective at 0.98 μM and showed a high rate of wound closure without skin irritation. Collectively, the NLCs developed for topical delivery of curcumin demonstrated prolonged and sustained release and improved wound healing activity, which indicates that curcumin-NLCs are a viable strategy for treating PU.

Keywords: Curcumin; nanostructured lipid carrier; physicochemical characterisation; pressure ulcers; toxicity

Abstrak

Ulser tekanan (PU) adalah lesi kronik dengan prevalens yang tinggi dalam populasi berisiko. Kurkumin, walaupun mempunyai pelbagai sifat terapeutik, penggunaannya sebagai agen terapeutik kulit adalah terhad akibat keterlarutan dan kebolehtelapan yang lemah. Kajian ini bertujuan untuk membangunkan pembawa lipid berstruktur nano (NLC) untuk memudahkan penggunaan kurkumin sebagai ubat topikal untuk penyembuhan luka dalam merawat PU. Kurkumin-NLC yang dioptimumkan telah dicirikan berdasarkan sifat fizikokimia, pembebasan dadah dan penelapan kulit, manakala keberkesanan dan ketoksikan dianalisis melalui daya maju sel, asai penyembuhan luka dan ujian iritasi kulit in vivo. Kurkumin-NLC yang dioptimumkan terdiri daripada 3.5% lipid pepejal, 1% surfaktan dan 2% surfaktan bersama dengan saiz zarah purata 134.68±6.0 nm, indeks polidispersiti 0.248±0.00, potensi zeta −44.94±5.44, peratusan kecekapan pengkapsulan 93.42±0.32% dan pemuatan dadah 0.11±0.00%. Kurkumin-NLCs menunjukkan sifat fizikokimia yang stabil dan pembebasan ubat yang dilanjutkan sehingga 48 jam dengan pembebasan kumulatif sebanyak 77.72% mengikut kinetik urutan pertama. Formulasi menunjukkan penelapan kurkumin yang lebih perlahan daripada kurkumin bebas. Tambahan pula, kurkumin-NLC yang selamat dan tidak toksik sangat berkesan pada 0.98 μM dan menunjukkan kadar penutupan luka yang tinggi tanpa iritasi kulit. Secara kolektif, NLC yang dibangunkan untuk penghantaran topikal kurkumin menunjukkan pembebesan yang berpanjangan dan berterusan serta aktiviti penyembuhan luka yang lebih baik, ini menunjukkan bahawa kurkumin-NLCs ialah strategi yang berdaya maju untuk merawat PU.

Kata kunci: Ketoksikan; kurkumin; pembawa lipid berstruktur nano; pencirian fizikokimia, ulser tekanan

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*Pengarang untuk surat-menyurat; email: email: hanifzulfakar@ukm.edu.my