Meloxicam encapsulated nanostructured colloidal self‐assembly for evaluating antitumor and anti‐inflammatory efficacy in 3D printed scaffolds

• Published in: Journal of biomedical materials research. Part A 2021-08, Vol.109 (8), p.1441-1456
• Main Authors: Rarokar, Nilesh, C, Ravikumar, Gurav, Shailendra, Khedekar, Pramod
• Format: Article
• Language: English
• Subjects: 3D printing; Anti-Inflammatory Agents, Non-Steroidal - administration & dosage; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Anticancer properties; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - pharmacology; Antitumor activity; Assembly; Breast Neoplasms - drug therapy; Cancer; Cell culture; Cell viability; Colloids; Colloids - chemistry; Controlled release; Cyclooxygenase 2 Inhibitors - administration & dosage; Cyclooxygenase 2 Inhibitors - pharmacology; Cytotoxicity; Drug Carriers - chemistry; Drug delivery; Drug delivery systems; Encapsulation; Estrogens; Female; Growth inhibition; Humans; Inflammation; Internalization; Invasiveness; MCF-7 Cells; Meloxicam; Meloxicam - administration & dosage; Meloxicam - pharmacology; Nanostructure; Nanostructures - chemistry; Optimization; Printing, Three-Dimensional; Prostaglandin endoperoxide synthase; Scaffolds; self‐assembly; Sustained release; Three dimensional printing; Toxicity
• ISSN: 1549-3296; 1552-4965
• DOI: 10.1002/jbm.a.37135

Nanostructured colloidal self‐assembly (NCS) is one of the most promising drug delivery carriers in cancer treatment. The present research work aimed towards synthesizing meloxicam (MLX) loaded NCS for its improved circulation half‐life and increased cellular internalization. NCS was formulated using glyceryl monoolein, Pluronic® F127, and MLX. Quality by Design experiments with a quadratic model was subjected to optimization of the formulation. The optimized NCS with an average particle size of 185.5 ± 3.02 nm showed higher MLX encapsulation (94.74 ± 3.41%) and sustained release behavior of MLX up to 24 hr. in vitro cytotoxicity of the developed NCS with MCF‐7 and MDA‐MB‐231 cell lines confirmed lower cell viability and a higher rate of cell growth inhibition. This MLX loaded NCS showed dual activity as an antitumor and anti‐inflammatory in highly invasive estrogen‐dependent MDA‐MB‐231 cells due to the high expression of cyclooxygenase‐2 (COX‐2). Besides, an activity of the MLX‐NCS was also observed in 3D printed MCF‐7 cells. This investigation shows the possible use of MLX‐NCS as an efficient cancer drug delivery system with excellent colloidal stability, sustained release of MLX, enhanced antitumor and anti‐inflammatory efficacy in 3D printed scaffolds. In contrast to toxicity study in 2D culture, the 3D constructs revealed the activity of the MLX via COX‐2 independent mechanism and demonstrated that the relationship between COX‐2 expression and antitumor activity of inhibitors is limited. In conclusion, the overall observations and results of this study strengthen the hypothesized development of NCS as a next‐generation therapeutics regimen for cancer therapy.