Schematic description of the hydrogel template approach for fabrication of homogeneous microstructures.
The first step is to form a pattern of vertical posts on a silicon wafer master template (A). If an intermediary silicone rubber template is to be used, then the vertical posts on the master template will become vertical cavities. On top of the master template is poured a warm aqueous gelatin solution, and then the temperature is lowered to form a gelatin hydrogel imprint (B). Once the gelatin layer is solidified, the gelatin mold is peeled off and the gelatin mold is placed on the flat surface to expose the cavities (C). The cavities in the gelatin mold are filled with a solution or a paste of drug/polymer mixture (D). In this study, poly(lactic-co-glycolic acid) (PLGA) was used as a model biodegradable polymer, and Nile Red, a fluorescent probe, was used for easy visualization unless specified otherwise. The organic solvent present inside the cavities is removed by drying, and the formed particles are collected by simply dissolving the hydrogel mold, followed by centrifugation or filtration (E).
Fabrication of homogeneous 10 µm PLGA microstructures using the hydrogel template method: (A) bright field image of a gelatin-hydrogel template; (B) fluorescence image of a hydrogel template filled with PLGA solution containing Nile Red; (C) SEM image of free standing PLGA microstructures obtained by pressing the gelatin template on a glass slide; (D) fluorescence image of free PLGA microstructures obtained after dissolving gelatin templates. (Scale bars correspond to 10 µm).
Fabrication of submicron PLGA particles by the hydrogel template approach. PLGA nanoparticles with diameter of 500 nm (A-D) and 200 nm (E-H). SEM images of gelatin templates (A & E); fluorescence image of a gelatin template filled with PLGA-Nile Red solution (B & F); SEM images of free PLGA particles (C & G); and fluorescence images of free PLGA particles (D & H). Recently, nanoparticles of 100 nm were made using the same technique but with different types of polymer templates. .
A gelatin template imprinted with a computer keyboard demonstrating the precision imprinting capability. (A) SEM image of a partially dried gelatin template with keyboard imprint as trenches; (B) fluorescence micrograph of a gelatin template filled with PLGA-Nile Red solution; (C) SEM image of a partially dried gelatin template with keyboard imprint as projections; (D) fluorescence micrograph of free letters obtained by dissolving the gelatin template in water.
The hydrogel template approach allows easy preparation of diverse structures and sizes. The best way of demonstrating the ability to make structures of various shapes, a computer keyboard was made using the hydrogel template method. A computer keyboard containing letters, numerals, and symbols presents rather complicated geometries. The gelatin templates can be used to imprint not only simple characters (such as I, O, C, etc,) but also complex geometries (such as &, $, #, π, etc.), thus demonstrating its precision imprinting capability. The space between each key is clearly visible and even the smallest spaces inside the letters retained their integrity. The line thickness of each character is 5 µm. The filling of the keyboard template with PLGA-Nile Red solution was very clean and no formation of scum layer was observed (B). The gelatin template can also be used to form the letters of the key board in the projection mode (C). The high precision imprinting capability was maintained. Panel D shows the letters obtained by dissolving the gelatin template in Panel B in water.
Microstructures in other shapes relevant to drug delivery can be easily made as shown below. (Back to the Top)
Fabrication of microparticles of different geometries by the hydrogel template approach. .
Drug-containing microparticles in the cylinder or disc shapes have been prepared for drug release experiments.
Drugs loaded PLGA particles in thedisc shape.
Felodipine release profile from PLGA microparticles (20 µm in diameter). The amount of felodipine in the microparticles was 50 % (w/w).
The drug loading efficiency was 80%
(n= 3). The release profile depends on the type of a drug, i.e., drug-PLGA interactions.
The drug release kinetics can be controlled independely of the drug-PLGA interactions.
The hydrogel template method can be used for making other nano/micro structures regardless of the nature of the material, because the cavities in the hydrogel template can be filled with any material of interest.