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Combinatorial drug-loaded quality by design adapted transliposome gel formulation for dermal delivery: In vitro and
Abdul Qadir1,2, Shehla Nasar Mir Najib Ullah3, Dipak Kumar Gupta2
1Department of Pharmaceutics, School of Pharmaceutical Education & Research, New Delhi, India.
Background:
Ursolic acid is a powerful drug that possesses many therapeutic properties, such as hepatoprotection, immunomodulation, anti-inflammatory, antidiabetic, antibacterial, antiviral, antiulcer, and anticancer activity. Centella asiatica (L.) Urban (Umbelliferae) contains a triterpene called asiatic acid, which has been used effectively in traditional Chinese and Indian medicine system for centuries. Anticancer, anti-inflammatory, and neuroprotective properties are only some of the many pharmacological actions previously attributed to asiatic acid .
Aim:
The present work developed an optimized combinatorial drug-loaded nano-formulation by Quality by design approach.
Materials And Methods:
The optimize transliposome for accentuated dermal delivery of dual drug. The optimization of drug-loaded transliposome was done using the "Box-Behnken design." The optimized formulation was characterized for vesicles size, entrapment efficiency (%), and in vitro drug release. Additionally, transmission electron microscopy (TEM), confocal laser scanning microscopy (CLSM), and dermatokinetic study were performed for further evaluation of drug-loaded optimized transliposome formulation.
Results:
The optimized combinatorial drug-loaded transliposome formulation showed a particle size of 86.36 ± 2.54 nm, polydispersity index (PDI) 0.230 ± 0.008, and an entrapment efficiency of 87.43 ± 2.66% which depicted good entrapment efficiency. In vitro drug release of ursolic acid and asiatic acid transliposomes was found to be 85.12 ± 2.54% and 80.23 ± 3.23%, respectively, as compared to optimized ursolic acid and asiatic acid transliposome gel drug release that was 67.18 ± 2.85% and 60.28 ± 4.12%, respectively. The skin permeation study of ursolic and asiatic acid conventional formulation was only 32.48 ± 2.42%, compared with optimized combinatorial drug-loaded transliposome gel (79.83 ± 4.52%) at 12 h. After applying combinatorial drug-loaded transliposome gel, rhodamine was able to more easily cross rat skin, as observed by confocal laser scanning microscopy, in comparison with when the rhodamine control solution was used.
Discussion:
The UA_AA-TL gel formulation absorbed more ursolic acid and asiatic acid than the UA_AA-CF gel formulation, as per dermatokinetic study. Even after being incorporated into transliposome vesicles, the antioxidant effects of ursolic and asiatic acid were still detectable. In most cases, transliposomes vesicular systems generate depots in the skin's deeper layers and gradually release the medicine over time, allowing for fewer applications.
Conclusion:
In overall our studies, it may be concluded that developed dual drug-loaded transliposomal formulation has great potential for effective topical drug delivery for skin cancer.
