Fourier-Transform Infrared Spectroscopy
Gelatin & Hyaluronic Acid Methacrylate (HAMA)
The platform is built with different materials. To examine each material and formation, they are measured in various ways, including FT-IR, XPS, microscopy, and SEM, to support what we provide below.
Fig.1 shows the FT-IR spectra of HAMA and gelatin, and their characteristic peaks are show in the table. The main characteristic peak positions are 3546 cm^-1 (O-H stretching vibration), 3421 cm^-1 (N-H stretching vibration on pyrrole), 2347 cm^-1 (O-C=O stretching vibration), 1533 cm^-1 (N-O stretching vibration), 1140 cm^-1 (in-plane C–H bending vibration), 1049 cm^-1 ( In-plane C-H deformation [ref1][ref2][ref3][ref4][ref5][ref6]. The result from FT-IR spectra proves that we successfully synthesized HAMA.
Fig.1 FT-IR spectra of gelatin (filler) and HAMA (shell) and the table of main peaks belongs to the gelatin and HAMA.
Silk Fibroin
In the near future, we want to use a more stable drug carrier and a slower release/diffusion rate to face different situations. Silk fibroin is the candidate we provide, and we’ve prepared it already. The FT-IR in Fig.2 shows the typical spectrum for silk fibroin. Next stage, we will load the AMPC and fabricate some different structures on it.
Fig.2 FT-IR spectrum of silk fibroin
X-ray Photoelectron Spectroscopy (XPS)
From the binding energies of the respective XPS C 1s and O 1s peaks, the formation of HAMA is confirmed by observing the chemical structure of HAMA via XPS in Fig.3. In C 1s spectrum, peaks at 284 and 285.4 eV are attributed to the sp2 atom, respectively. In addition, O^1+ and O2+ could be identified at 531.3 and 533 eV.
Fig.3 The XPS spectra of HAMA, and the C and O profile peak of HAMA
HAMA Shell
In Fig.4, an optical microscopy image of a microneedle patch is presented. The homogeneous distribution of the pyramid-like tips fabricated by gelatin can be recognized. Fig.4 shows a microneedle patch after curing a HAMA coating by photo-linkable technique.
Fig.4 The optical microscopy image of microneedle patch
We prepared a HAMA film on a plastic plate to observe whether the film can be dissolved by water or not. Fig.5a shows the film after one week still can’t degrade by water. After the above experiment, we switched respectively the media to E. coli and S. aureus to simulate the wound with bacteria. Fig.5b can observe the HAMA film was erased by S. aureus after 30 min. This evidence can provide critical information for us that the HAMA can be broken by S. aureus.
Fig.5a The time dependent evolution image of HAMA film under various medium
Fig.5b The time dependent evolution image of HAMA film under various medium
In Fig.6a, the microneedle borders without the HAMA shell were less sharp as observed by dissecting microscopy, while the photocured-prepared system had a sharper appearance and better physical properties. In fig.6b we took the larger magnification picture of the microneedle to check the hollow structure in the center of the microneedle.
Fig.6a The optical microscopy image of microneedle with dye
Fig.6b The larger magnification image of microneedle
Field Emission Scanning Electron Microscopy
Fig.7a provides field emission scanning electron microscopy (FESEM) morphological images of the microneedles. In Fig.7b, the FESEM image of the microneedles with the HAMA coat shows the sharper edge after UV curing, with the same results as above.
Fig.7a The FESEM image of microneedle
Fig.7b The FESEM image of microneedle with the HAMA coat
On Plate Test
The same volume and different concentrations of the drug were added to the carrier, and the co-incubation with Staphylococcus aureus showed that he could successfully carry the drug, and the drug was still effective.
Fig.8 The microneedle patch with various concentration AMPC incubated with S. aureus
Dye Release Test
The drugs were replaced by pigment mixed with gelatin immersed in the water can be released after one hour, which means this system can use as the drug carrier.
Fig.9 Digital image of microneedle patch use as the drug carrier system
In Fig.10, we performed puncture tests using pigskin to simulate human skin, and the results showed that the microneedle patch can effectively puncture and retain the drug. Below is a photo of a pigskin puncture showing the effective release of our microneedles.
Fig.10 The microneedle after releasing in pigskin
Biocompatibility
We conducted MTT tests on our microneedles to assess their biocompatibility. In order to prepare the extract solutions, equally-sized PEGDA hydrogels and microneedle parts were immersed in 1 mL of culture medium and incubated for 24 h. NIH 3T3 cells were placed in 96-well cell culture dishes for 24 h to ensure engraftment. The control group was added to a 24 h culture medium. Using the microplate, read the OD value reader, cell viability can be obtained. In Fig.11 the results showed that cells in both positive and negative groups grew and replicated well, demonstrating the biocompatibility of our microneedle patch.
Fig.11 MTT test of our microneedle
Mechanical Analysis of Microneedle Patch
In order to overcome the skin's barrier and effectively deliver drugs into the skin, insertion ability are critical for microneedle patches. As described above, drug-loaded MN patches were prepared from HAMA shells with different centrifugation times and gelatin fillers. Micromechanical testing machines equipped with mechanical sensors were used to quantify the mechanical properties. The vertical removal sensor slowly presses the MN sample fixed on the platform. To obtain the front stroke curve, record the changing force and stroke of the sensor during the test that all microneedle patches show reduction and deformation but no bending or fracture after compression with a 42N force. This indicates that the 2 min centrifugation time is not as mechanically strong as the other times. To facilitate S. aureus to degrading the shell, we chose “2 min” to make microneedle patch in the end.
Fig.12a Mechanical analysis of microneedle patches
Fig.12b Mechanical analysis of microneedle patches with different centrifugation times
Reference
- Nieuwenhuizen, M.S.; Nederlof, A.J.; Barendsz, A.W., (Metallo)-phthalocyanines as chemical interfaces on a surface acoustic wave gas sensor for nitrogen dioxide. Analytical Chemistry 1988, 60 (3), 230-235.
- Moriya, K.; Enomoto, H.; Nakamura, Y., Characteristics of the substituted metal phthalocyanine NO2 sensor. Sensors and Actuators B: Chemical 1993, 13 (1), 412-415.
- Zhu, D. G.; Petty, M. C.; Harris, M., An optical sensor for nitrogen dioxide based on a copper phthalocyanine Langmuir—Blodgett film. Sensors and Actuators B: Chemical 1990, 2 (4), 265-269.
- Sergeyeva, T. A.; Lavrik, N. V.; Rachkov, A. E.; Kazantseva, Z. I.; Piletsky, S. A.; El'skaya, A. V., Hydrogen peroxide – sensitive enzyme sensor based on phthalocyanine thin film. Analytica Chimica Acta 1999, 391 (3), 289-297.
- Gu, C.; Sun, L.; Zhang, T.; Li, T.; Zhang, X., High-sensitivity phthalocyanine LB film gas sensor based on field effect transistors. Thin Solid Films 1998, 327-329, 383-386.
- Jakubik, W.; Urbańczyk, M.; Stanislaw, K.; Bodzenta, J., Bilayer structure for hydrogen detection in a surface acoustic wave sensor system. Sensors and Actuators B: Chemical 2002, 82, 265-271.