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Sains Malaysiana 55(4)(2026): 601-612
http://doi.org/10.17576/jsm-2026-5504-01
Preservation of Physicochemical Properties in
Freeze-Dried Betaine-Glucose Eutectic-Based Curcumin Niosomes using Mannitol as Cryoprotectant
THAARANNI BASHKERAN1, FAIZNUR MOHD FUAD2,
TRUNG XUAN NGO3 & MASRINA MOHD NADZIR1,*
1School of Chemical
Engineering, Tuanku Syed Sirajuddin Engineering
Campus, Universiti Sains Malaysia, 14300 Nibong Tebal, Pulau Pinang, Malaysia
Received:
15 October 2025/Accepted: 9 March 2026
Abstract
This study investigates the preservation of physicochemical properties
in freeze-dried eutectic-based curcumin niosomes using mannitol. Three
niosomes’ formulations, incorporating various natural deep eutectic solvents
(NADES) alongside a blank formulation devoid of NADES, were subjected to
freeze-drying processes. The particle size (Z-average), polydispersity index
(PDI), entrapment efficiency, and zeta potential of the freeze-dried niosomes
were assessed upon rehydration. Niosomes were prepared with varying
concentrations of the cryoprotectant, mannitol, relative to non-ionic
surfactants. Although the pharmaceutical potential of curcumin niosomes is
recognized, this research focuses on the specific synergy between the internal
BET-GLU NADES core and the external mannitol in maintaining niosome integrity
after lyophilization. The incorporation of mannitol markedly improved the
physicochemical properties of the freeze-dried eutectic-based niosomes. The use of BET-GLU NADES
in the niosome formulation resulted in a reduction in
particle size from 870.0 ± 15.52 nm to 418.07 ± 5.95 nm, concomitant with a
decrease in PDI from 0.34 ± 0.016 to 0.12 ± 0.04. Moreover, the entrapment
efficiency of curcumin in the BG-NADES formulation was 75.75 ± 6.12%, which was
higher than the blank formulation (37.52 ± 2.19%). The synergistic addition of
10 g/g of mannitol was identified as the most effective concentration, further increasing
entrapment efficiency to 93.24 ± 3.21%. Additionally, the zeta potential
slightly increased in the negative direction from -38.87 ± 0.32 mV to -45.33 ±
3.99 mV with the incorporation of mannitol. The in vitro drug-release
profiles, demonstrating sustained-release kinetics, and the antioxidant assays
indicated preserved activity. This
study highlights the critical synergistic role of mannitol and NADES in
preserving the physicochemical properties of freeze-dried eutectic-based
curcumin niosomes, providing a precise framework for stable nano-delivery
systems.
Keywords: Cryoprotectant; curcumin; drug delivery; freeze-drying; niosomes Abstrak
Penyelidikan ini mengkaji pemeliharaan sifat fizikokimia dalam niosom kurkumin berasaskan eutektik beku-kering menggunakan manitol. Tiga formulasi niosom, yang menggabungkan pelbagai pelarut eutektik dalam semula jadi (NADES) bersama-sama satu formulasi sifar tanpa NADES, telah melalui proses beku-kering. Saiz zarah (purata-Z), indeks polidispersiti (PDI), kecekapan pemerangkapan dan potensi zeta niosom beku-kering dinilai selepas penghidratan semula. Niosom disediakan dengan kepekatan krioprotektan, manitol yang berbeza-beza berbanding surfaktan bukan ion. Walaupun potensi farmaseutikal niosom kurkumin telah diiktiraf, penyelidikan ini memberi tumpuan kepada sinergi khusus antara teras dalaman NADES BET-GLU dan manitol luaran dalam mengekalkan integriti niosom selepas liofilisasi. Penggabungan manitol telah menambah baik sifat fizikokimia niosom berasaskan eutektik beku-kering dengan ketara. Penggunaan NADES BET-GLU dalam formulasi niosom menghasilkan pengurangan saiz zarah daripada 870.0 ± 15.52 nm kepada 418.07 ± 5.95 nm, disertakan dengan penurunan PDI daripada 0.34 ± 0.016 kepada 0.12
± 0.04. Selain itu, kecekapan pemerangkapan kurkumin dalam formulasi BG-NADES adalah 75.75 ±
6.12%, iaitu lebih tinggi berbanding formulasi sifar (37.52 ± 2.19%). Penambahan sinergi manitol pada 10 g/g telah dikenal pasti sebagai kepekatan paling berkesan,
yang meningkatkan lagi kecekapan pemerangkapan kepada 93.24 ± 3.21%. Tambahan pula, potensi zeta meningkat sedikit ke arah negatif daripada -38.87 ± 0.32 mV kepada -45.33 ± 3.99 mV dengan penggabungan manitol. Profil pembebasan dadah in vitro menunjukkan kinetik pembebasan berterusan dan ujian antioksidan menunjukkan aktiviti yang dikekalkan. Kajian ini menyerlahkan peranan sinergi kritikal antara manitol dan NADES dalam memelihara sifat fizikokimia niosom kurkumin berasaskan eutektik beku-kering, sekali gus menyediakan rangka kerja yang tepat bagi sistem nano-penyampaian yang stabil.
Kata kunci: Krioprotektan; kurkumin; niosom; pengeringan beku; penghantaran dadah
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*Corresponding author; email: chmasrina@usm.my
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