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CHI TIẾT
Nghiên cứu mối liên quan nhân quả và tối ưu hóa công thức giá mang nano lipid chứa quercetin và curcumin
Study on cause - effect relations and optimization of quercetin and curcumin loaded nanostructured lipid carriers
Nguyễn Đức Hạnh, Nguyễn Thị Quỳnh Trang, Tần Bảo Châu, Đỗ Quang Dương
Số: 526 - Tháng 2/2020 - Trang 23-29

Quercetin là một flavonoid có tác dụng chống oxi hóa mạnh, làm giảm các tổn thương do tia UV, tăng sinh collagen, làm chậm quá trình lão hóa da, kháng viêm và làm lành vết thương hiệu quả. Curcumin là polyphenol có tác dụng chống oxi hóa, kháng viêm, hỗ trợ làm lành sẹo, vết bỏng và phục hồi nhanh các vết thương hở trên da. Việc kết hợp cả hai hoạt chất giúp tối ưu hóa hiệu quả điều trị và tăng khả năng hấp thu trên da của hoạt chất.

Tuy nhiên, độ tan của quercetin và curcumin trong nước thấp (< 1 µg/ml), độ ổn định kém. Đây là những vấn đề cần được khắc phục trong quá trình phát triển các dạng bào chế dùng trên da cho cả hai hoạt chất này. Hiện nay, có nhiều kỹ thuật có thể cải thiện độ tan, tăng độ ổn định cho hoạt chất như hệ vi tự nhũ, hệ vi nhũ tương, hệ liposome, giá mang nano lipid (NLC-Nanostructured lipid carriers),… Trong hệ NLC, sự kết hợp lipid lỏng và lipid rắn giúp ức chế quá trình tái kết tinh của phân tử hoạt chất, tăng khả năng tải và chống hiện tượng hoạt chất bị đẩy ra khỏi tiểu phân trong quá trình bảo quản. Hệ NLC có kích thước nhỏ giúp tăng tính thấm của hoạt chất qua da. Vì vậy, hệ NLC được ứng dụng để cải thiện sinh khả dụng qua da những hạn chế kể trên của quercetin và curcumin.

Hiện nay, chưa có công bố về việc nghiên cứu phối hợp đồng thời hai hoạt chất quercetin và curcumin trên một hệ NLC. Việc cạnh tranh giữa 2 hoạt chất cũng như ảnh hưởng của thành phần tá dược lên khả năng tải và khả năng bắt giữ đồng thời hai hoạt chất quercetin và curcumin trên cùng một hệ NLC chưa được nghiên cứu, đánh giá. Vì vậy, nghiên cứu được thực hiện nhằm mục tiêu  thiết lập mối liên quan nhân quả và tối ưu hóa công thức giá mang nano lipid chứa đồng thời quercetin và curcumin.

            Nguyên liệu, hóa chất

Quercetin (độ tinh khiết 97,83 %) và curcumin (độ tinh khiết 96,89 %); Maisine 35-1, Capryol 90, Labrafac lipophile, Labrafac PG, Labrafac CC, Plurol Oleique CC 497, Labrasol, Transcutol P, Compritol 888ATO, Geleol và PrecirolATO 5; Cremophor RH 40, Cremophor EL, Lutrol E-400, Miglyol 812N.

Phương pháp nghiên cứu

- Khảo sát và lựa chọn tá dược hệ QC-NLC

+ Độ tan của quercetin hoặc curcumin trong tá dược lỏng

+ Tính tan riêng của quercetin hoặc curcumin trong tá dược lipid rắn

+ Khảo sát lựa chọn chất diện hoạt và chất đồng diện hoạt

- Phương pháp điều chế hệ QC-NLC

- Nghiên cứu mối liên quan nhân quả và tối ưu hóa công thức hệ QC-NLC

- Phương pháp xác định kích thước tiểu phân và chỉ số đa phân tán

- Khả năng bắt giữ và tải hoạt chất

Kết luận

            Đây là nghiên cứu đầu tiên phối hợp đồng thời 2 hoạt chất quercetin và curcumin trên cùng một hệ NLC. Các tá dược Capryol 90, Compritol 888ATO, Cremophor RH40, Lutrol E-400 đã được lựa chọn làm tá dược lipid lỏng, lipid rắn, chất diện hoạt và chất đồng diện hoạt cho hệ QC-NLC. Mối liên quan nhân quả giữa tínhchất của hệ QC-NLC và thành phần tá dược đã được thiết lập và công thức hệ QC-NLC đã được tối ưu hóa làm cơ sở cho các nghiên cứu tiếp theo.

As nanostructured lipid carriers (NLC). which well improve the solubility, drug loading and increases the absorption of the active ingredients through the skin, were.investigated for the two active compounds of low solubility: Quercetin and Curcumin. For this, the cause-effect relations was estimated and the formulation of quercetin and curcumin loaded nanostructured lipid carriers (QC-NLC) was optimized, both by the BCPharSoft OPT software. Excipient screening was based on quercetin and curcumin solubilities and the compatibility of excipient mixtures. QC-NLC was prepared by hot ultrasonication. Ten experiments were designed by Design-Expert 6.0.6 for evaluating the effect of 3 independent variables (liquid lipid to total lipid ratio, surfactant concentration, total lipid concentration) on 6 dependent variables (particle size (PS), polydispersity index (PDI), quercetin entrapment efficiency (EEquer), curcumin entrapment efficiency (EEcur), quercetin loading capacity (DLquer), curcumin loading capacity (DLcur). An HPLC method for quantitative determination of quercetin and curcumin was validated following ICH guidelines. The optimized QC-NLC system was evaluated for its pH, zeta potential, morphology, average particle size and preliminary assessment of stability. It was found that all investigated factors including liquid lipid to total lipid ratio, surfactant concentration, total lipid concentration showed significant effects on PS, PDI, EE and DL. PS, PDI, EEquer, EEcur, DLquer and DLcur of the optimal QC-NLC system (these were 21.77 ± 3.68 nm; 0.13 ± 0.11; 99.85% ± 0.06; 99.99%, 2.42 ± 0.05; 2.32 ± 0.09, respectively). The obtained QC-NLC system possessed an average pH of 4.17, a zeta potential of about -5.19 mV, showed desirable stability of the particle size and good protection of active ingredient during 2-week period. This report is the first one on the cause-effect relations and optimization of QC-NLC, would be useful for topical bioavailability enhancement of quercetin and curcumin.

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