Unveiling the Power of CO₂ Gas Hydrates: Precise Size Control and Enhanced Drug Encapsulation for Next-Generation Niosomes

This study reports the first-time application of the CO2 gas hydrate method for the size reduction of multilayered niosomes loaded with Tretinoin. This novel technique was developed by integrating pharmaceutical science with chemical engineering principles. This approach enabled the efficient incorporation of low-efficiency drugs into niosomes while simultaneously reducing their diameter. Additionally, this innovative method had the ability to separate niosomes of different sizes. In detail, a series of four different parts of hydrate experiments were conducted to study the effects of various formulating parameters through the gas hydrate method. First, niosomes were shaped with three distinct molar masses and experienced the hydrate tests for size reduction at 30 bar and 275 K. In the second part of hydrate experiments, the entrance niosomes had larger diameter with the same situation of hydrate tests along with 83% of diameter reduction. Also, at the third part of hydrate experiments, the maximum diameter reduction of 68% was achieved with two hydrate formation stages at 30 bar and 275 K. Afterward, in the fourth part, the focus shifted toward investigating the impact of the ratio between the volume of the solution and the pressure of the input gas. The greatest diameter reduction (76%) occurred at a volume of 35 cc and a pressure of 30 bar in this part. The results demonstrated the feasibility of using this approach to effectively reduce niosome size and improve their functionality.