Yingtai: Application of Vacuum Freeze-Drying Technology in Microsphere Development

Yingtai: Application of Vacuum Freeze-Drying Technology in Microsphere Development

Freeze-drying technology, as an effective preservation method, is widely used in the pharmaceutical, biotechnology, and materials science fields, particularly demonstrating unique advantages in the preparation of microsphere formulations. Microspheres serve as drug carriers that enable sustained or controlled release, enhancing efficacy while reducing side effects. The application of freeze-drying technology in the preparation of drug-loaded microspheres, such as PLGA (poly-lactic-co-glycolic acid) microspheres and chitosan microspheres, is particularly noteworthy.

The freeze-drying process is crucial for controlling the burst release of hydrophilic macromolecular drugs (e.g., FITC-labeled dextran) from PLGA microspheres. During freezing and subsequent drying, microporous channels form within the microspheres, facilitating the rapid diffusion of encapsulated molecules, leading to increased release. Confocal microscopy has been utilized to analyze this mechanism, suggesting that vacuum drying can more effectively reduce drug burst release compared to freeze-drying. Various drying methods have been compared for optimizing the drug release behavior of microspheres. The choice of drying method impacts drug release profiles; a 2019 study compared vacuum freeze-drying and vacuum drying's effects on the structure, morphology, and in vitro release characteristics of risperidone-loaded PLGA microspheres. Results indicated that microspheres produced by freeze-drying exhibited higher porosity, resulting in faster drug release rates. This research underscores the importance of selecting drying processes for precise control of drug release curves.

Earlier reports described the use of human serum albumin and mercaptopurine encapsulated in magnetic microspheres, creating a novel drug carrier for treating gastrointestinal tumors. After oral administration, these magnetic microspheres can be attracted to specific target areas using an appropriately strong magnet, achieving the desired concentration. The characteristics of this carrier include:

1. Reduced drug dosage due to localized absorption around the target area, leading to decreased distribution in other regions and consequently lowering the overall dosage.

2. Minimization of drug side effects on normal tissues, particularly reducing damage to the liver, spleen, kidneys, and other components of the hematopoietic and excretory systems.

3. Accelerated onset of action and improved efficacy.

The preparation of magnetic microspheres requires key raw materials, including magnetic materials, polymer matrices, and possible additives. The materials and finished products must meet specific technical requirements:

1. The carrier's structural components must be metabolizable in vivo, with non-toxic metabolic byproducts excreted within a certain timeframe.

2. Non-biodegradable ferromagnetic particles should generally have diameters between 10-20 μm, not exceeding 100 μm (with injectable particle sizes below 1-3 μm), maintaining adequate repulsion to prevent aggregation and vascular blockage. They should uniformly distribute in capillaries and diffuse to target areas.

3. Good biocompatibility and minimal antigenicity are essential.

4. Ferromagnetic materials should not remain in large blood vessels under a defined external magnetic field but should stay within target capillaries.

5. The microspheres must transport sufficient drug quantities while possessing adequate mechanical strength and biodegradation rates, with suitable drug release speeds to ensure substantial drug availability at the target site.

Domestic studies have reported on the design of 5-Fu magnetic microsphere carriers, which, after oral administration, adhere to cancerous areas in the esophagus under an external magnetic field, releasing 5-Fu for absorption by cancerous tissues to treat esophageal cancer. This approach allows for high local concentrations with smaller dosages, reducing drug toxicity in normal tissues while enhancing therapeutic effects. Additionally, strong magnetic fields exhibit anti-cancer properties.