Formulation of Dacarbazine-Loaded Cubosomes—Part I: Influence of Formulation Variables

Abstract

Abstract. The purpose of this study was to investigate the combined influence of three-level, three-factor variables on the formulation of dacarbazine (a water-soluble drug) loaded cubosomes. Box-Behnken design was used to obtain a second-order polynomial equation with interaction terms to predict response values. In this study, the selected and coded variables X 1 , X 2 , and X 3 representing the amount of monoolein, polymer, and drug as the independent variables, respectively. Fifteen runs of experiments were conducted, and the particle size (Y 1 ) and encapsulation efficiency (Y 2 ) were evaluated as dependent variables. We performed multiple regression to establish a full-model second-order polynomial equation relating independent and dependent variables. A second-order polynomial regression model was constructed for Y 1 and confirmed by performing checkpoint analysis. The optimization process and Pareto charts were obtained automatically, and they predicted the levels of independent coded variables X 1 , X 2 , and X 3 (−1, 0.53485, and −1, respectively) and minimized Y 1 while maximizing Y 2 . These corresponded to a cubosome formulation made from 100 mg of monoolein, 107 mg of polymer, and 2 mg with average diameter of 104.7 nm and an encapsulation efficiency of 6.9%. The Box-Behnken design proved to be a useful tool to optimize the particle size of these drug-loaded cubosomes. For encapsulation efficiency (Y 2 ), further studies are needed to identify appropriate regression model.

Development of nanostructured lipid carrier for dacarbazine delivery

“…Several previous attempts have been made to develop drug delivery vehicles for Dac to improve the therapeutic profile of the drug [16,18,19,34]. However, the low drug encapsulation and loading efficiency present critical limitations for these new formulations to achieve a real benefit.…”

Formulation of Dacarbazine-loaded Cubosomes. Part III. Physicochemical Characterization

“…The method of preparation of DTIC-loaded cubosomes was adapted from previous work of Esposito et al (17)(18)(19). Briefly, for each sample, a volume of 15 ml chloroform was used to completely dissolve 500 mg GMO and 75 mg F127.…”

“…Sample #1 and control #1 were formulated using the authors' published method related to the study of formulation variables (18). Basically, drug-loaded sample #1 (F1+) and control #1 (blank cubosomes, F1−) were prepared in the same condition, namely at homogenization speed of 13,500 rpm for 1 min duration at 80°C±2°C.…”

Nanostructured Cubosomes in a Thermoresponsive Depot System: An Alternative Approach for the Controlled Delivery of Docetaxel

“…In recent years, there has been a growing interest among researchers in exploring the pharmaceutical applications of cubosomes and cubosomebased systems. With the recent developments in the technology, experience and expertise in the area of nano-pharmaceuticals, cubosome-based systems are being actively pursued as potential alternatives to now-common systems such as liposomes and niosomes (10,11). Cubosomes are made up of a binary system of monoolein and water, where the monoolein acts as a precursor for lipid bilayer, which divides the hydrophilic regions of cubic phases (10,12).…”

“…With the recent developments in the technology, experience and expertise in the area of nano-pharmaceuticals, cubosome-based systems are being actively pursued as potential alternatives to now-common systems such as liposomes and niosomes (10,11). Cubosomes are made up of a binary system of monoolein and water, where the monoolein acts as a precursor for lipid bilayer, which divides the hydrophilic regions of cubic phases (10,12). This binary system can self-assemble into thermodynamically stable bi-continuous, cubic, liquid-crystalline phases (13).…”