(M1430-05-30) Formulation Development of PEGylated Deferoxamine Carbon Nanoparticles Gel for Topical Application

Purpose: The focus of current research work is to develop and evaluate gel formulation of PEGylated deferoxamine conjugated carbon nanoparticles (CNP) for topical delivery. The gel formulations were evaluated for physicochemical attributes (viscosity and mechanical properties) and permeation through pig ear.

Methods: The morphology of CNP was performed by transmission electron microscope (TEM). A novel size exclusion HPLC analytical method was developed and validated for CNP quantification in various samples. The CNP gel formulations containing Carbopol^® 974P and Transcutol (TC) were prepared. The CNP gel formulation was evaluated for mechanical properties, permeation, flux, and retention via pig ear skin using Franz diffusion cells. The permeation medium used was phosphate buffer pH 7.4 (0.2M) as a medium. The samples were analyzed for steady-state flux from the permeation data between 2 to 6 h.

Results: Aggregates of spherical CNP particles were observed in TEM image analysis. The absence of medium and gel formulation matrix interference with the CNP peak demonstrated the selectivity of the devised HPLC technique. The novel validated HPLC analytical method met the preset criteria of system suitability parameters such as retention time (RSD ≤2%), peak area (RSD ≤2%), capacity factor ( >3), and USP tailing factor ( < 2) for CNP peak. The correlation coefficient was >0.999. Accuracy and precision were calculated from the quality control samples, and RSD was found to be < 2%. The cohesiveness of CNP gel formulations was recorded in the range 7.8±0.1 to 11.2 ± 0.8 g.s, whereas, adhesiveness of the CNP topical gel formulations were found to be in the range of -5.7±0.16 g.s. The cumulative permeation of CNP from the gel formulations were 15.2±1.6 to 37.7±4.9 µg/cm² and 23.2±2.3 to 70.9±12.2 µg/cm² in 1 and 6 h, respectively, through the pig ear skin with a high steady-state flux in the range of 0.8±0.3 to 6.6±2.1 µg/cm²/h between 2 to 6 h. The gel formulation containing 2% Carbopol and 20% TC provided maximum permeation (70.9±12.2 µg/cm²) in 6 h. The retained CNP in the skin was found to be 5.6±0.3 to 38.8±8.8 µg/g.

Conclusion: The newly developed and validated HPLC analytical method is simple, sensitive, and specific to CNP, and it can quantify the least quantity of it in samples. The CNP gel formulation exhibited high permeation with zero lag time, and a high steady-state flux was recorded between 0 to 2 h. Thus, the gel formulation of CNP has the potential for topical and systemic administration of the drug. In conclusion, the CNP gel formulation could be a promising approach for local and systemic delivery of drug by topical and transdermal routes.

Acknowledgements: This work was funded by Presidential Clinical Research Partnership Grants between TAMU, College Station, and Houston Methodist Hospital and Research Institute.