Transethosomal Gel for the Topical Delivery of Celecoxib: Formulation and Estimation of Skin Cancer Progression
Ahmed A H Abdellatif1,2, Basmah Nasser Aldosari3, Amal Al-Subaiyel1
1Department of Pharmaceutics, College of Pharmacy, Qassim University, Qassim 51452, Saudi Arabia.
Abstract:
The topical delivery of therapeutics is a promising strategy for managing skin conditions. Cyclooxygenase-2 (COX-2) inhibitors showed a possible target for chemoprevention and cancer management. Celecoxib (CXB) is a selective COX-2 inhibitor that impedes cell growth and generates apoptosis in different cell tumors. Herein, an investigation proceeded to explore the usefulness of nano lipid vesicles (transethosomes) (TES) of CXB to permit penetration of considerable quantities of the drug for curing skin cancer. The prepared nanovesicles were distinguished for drug encapsulation efficiency, vesicle size, PDI, surface charge, and morphology. In addition, FT-IR and DSC analyses were also conducted to examine the influence of vesicle components. The optimized formulation was dispersed in various hydrogel bases. Furthermore, in vitro CXB release and ex vivo permeability studies were evaluated. A cytotoxicity study proceeded using A431 and BJ1 cell lines. The expression alteration of the cyclin-dependent kinase inhibitor 2A (CDKN2A) gene and DNA damage and fragmentation using qRT-PCR and comet assays were also investigated. Optimized CXB-TES formulation was spherically shaped and displayed a vesicle size of 75.9 ± 11.4 nm, a surface charge of -44.7 ± 1.52 mV, and an entrapment efficiency of 88.8 ± 7.2%. The formulated TES-based hydrogel displayed a sustained in vitro CXB release pattern for 24 h with an enhanced flux and permeation across rat skin compared with the control (free drug-loaded hydrogel). Interestingly, CXB-TES hydrogel has a lower cytotoxic effect on normal skin cells compared with TES suspension and CXB powder. Moreover, the level of expression of the CDKN2A gene was significantly (p ≤ 0.01, ANOVA/Tukey) decreased in skin tumor cell lines compared with normal skin cell lines, indicating that TES are the suitable carrier for topical delivery of CXB to the cancer cells suppressing their progression. In addition, apoptosis demonstrated by comet and DNA fragmentation assays was evident in skin cancer cells exposed to CXB-loaded TES hydrogel formulation. In conclusion, our results illustrate that CXB-TES-loaded hydrogel could be considered a promising carrier and effective chemotherapeutic agent for the management of skin carcinoma.
Insights
This study developed transethosomes (TES) loaded with celecoxib (CXB) for effective topical skin cancer treatment. The CXB-TES hydrogel demonstrated enhanced drug delivery and suppressed cancer cell progression with reduced toxicity.
Area of Science:
- Nanotechnology
- Dermatology
- Oncology
Background:
- Topical drug delivery offers a promising strategy for managing skin conditions.
- Celecoxib (CXB), a selective cyclooxygenase-2 (COX-2) inhibitor, shows potential in cancer chemoprevention by impeding cell growth and inducing apoptosis.
- Effective topical delivery of CXB for skin cancer management requires advanced carrier systems to enhance skin penetration.
Purpose of the Study:
- To explore the efficacy of transethosomes (TES) for topical delivery of celecoxib (CXB) to treat skin cancer.
- To characterize the physicochemical properties of CXB-loaded TES and evaluate their performance in a hydrogel formulation.
- To assess the therapeutic potential of CXB-TES hydrogel through in vitro and ex vivo studies, including cytotoxicity, gene expression, and DNA damage.
Main Methods:
- Preparation and characterization of CXB-loaded TES, including vesicle size, surface charge, and encapsulation efficiency.
- Formulation of CXB-TES into a hydrogel base and evaluation of in vitro drug release and ex vivo skin permeation.
- Cytotoxicity assessment on A431 and BJ1 cell lines, qRT-PCR for CDKN2A gene expression, and comet assays for DNA damage and fragmentation.
Main Results:
- Optimized CXB-TES were spherical with a size of 75.9 ± 11.4 nm, surface charge of -44.7 ± 1.52 mV, and 88.8 ± 7.2% entrapment efficiency.
- The TES-based hydrogel exhibited sustained in vitro CXB release over 24 h and enhanced permeation across rat skin compared to the free drug.
- CXB-TES hydrogel showed reduced cytotoxicity on normal skin cells, significantly decreased CDKN2A gene expression in cancer cells, and induced apoptosis, indicating suppressed cancer progression.
Conclusions:
- CXB-loaded TES represent a suitable nanocarrier for topical delivery of celecoxib for skin cancer management.
- The developed TES-based hydrogel formulation is a promising chemotherapeutic agent for effectively treating skin carcinoma.
- This approach offers enhanced drug delivery, targeted action, and reduced side effects for topical cancer therapy.
