Comparison of naproxen-loaded zeolitic imidazolate frameworks (ZIF) and halloysite nanotube-zif composites with 3D printed PLA embedded in gelatin hydrogel

Abstract

Nanomedicine is an interdisciplinary discipline that integrates nanotechnology with biomedical sciences. It brings about a revolution in illness management by introducing revolutionary methods in diagnosis, treatment, and prevention. A crucial element of this development is the investigation of nanocarriers, vital constituents in sophisticated pharmaceutical delivery systems that aim to surpass biological obstacles and facilitate precise and regulated drug discharge. Within this framework, the study specifically examines two types of inorganic nanocarriers, namely Zeolitic Imidazolate Frameworks (ZIFs) and Halloysite Nanotubes (HNTs). These two nanocarriers possess similar distinctive characteristics, which make them well-suited for a comparative analysis. ZIFs, which are categorized as metal-organic frameworks (MOFs), possess a wide range of beneficial characteristics that are essential for their function as nanocarriers in nanomedicine and drug delivery systems. The characteristics of these materials encompass high porosity, modifiable size and structure, convenient surface alteration, minimal toxicity, significant loading capacity, improved stability, favorable biocompatibility, water solubility, and biodegradability. ZIFs exhibit pH-responsive properties, allowing for the targeted release of medications in response to changes in acidity. This attribute improves the accuracy and timeliness of drug administration. In comparison, Halloysite Nanotubes (HNTs) belong to a different category of inorganic nanocarriers that offer exceptional characteristics, making them extremely desirable for use in medicinal applications. The inherent tubular morphology of HNTs enhances their biocompatibility, extensive surface area, and capacity for surface modification, making them highly favorable for applications as drug delivery systems. HNTs possess the ability to release drugs in a controlled and prolonged manner, while also having less toxic effect and being naturally abundant. This makes them highly adaptable and beneficial in the field of pharmaceutical sciences. Furthermore, HNTs possess antibacterial properties, which are essential in situations when it is necessary to prevent the growth of germs. The pH-responsive drug release properties of HNTs further facilitate accurate and focused medication delivery. Therefore, HNT- ZIF combination was designed and synthesized to analyze how the properties of HNT effect the properties of ZIF, comparing with synthesized ZIF. Hydrogels that are known for their capacity to absorb water and compatibility with living organisms and are crucial in the field of biomedicine, particularly in applications such as wound dressings and drug delivery systems. The scaffold structures used in tissue engineering, particularly when paired with poly(lactic acid) (PLA), play a significant role in promoting cell proliferation and tissue regeneration. PLA offers advantages such as providing structural reinforcement and undergoing a progressive process of biodegradation. The combination of hydrogel and PLA scaffold, facilitated by 3D printing technology, improves accuracy and personalization. The benefits of utilizing 3D printing in tissue engineering encompass the capacity for replication, expandability, and the capability to fabricate structures with regulated porosity. The combination of these elements has the potential to generate groundbreaking solutions in the field of regenerative medicine. The aim of the study was to combine two distinct patches: one comprising a composite gelatin hydrogel and PLA scaffold with Naproxen, a nonsteroidal anti-inflammatory drug, loaded ZIF embedded within it, and the other comprising a composite gelatin hydrogel and PLA scaffold with Naproxen loaded HNT-ZIF embedded within it. The objective is to evaluate and compare the drug loading capacity, drug release behavior and pH responsiveness To determine their properties using various techniques, including scanning electron microscopy (SEM), Liquid Chromatography–Mass Spectrometry (LC-MS), Energy-Dispersive X-Ray Spectroscopy (EDS), swelling capacity determination, drug release analysis, pH responsiveness analysis, and in vitro cytotoxicity study. They were successfully completed. Based on examinations, ZIF and HNT-ZIF composite were synthesized successfully and their bonds and each size of synthesized nanoparticles were quite similar with literatures, which FT-IR graphs and SEM images proved. Data of EDS and FT-IR demonstrates that Naproxen was loaded into synthesized nanocarriers and according to LC-MS results show approximately %92 efficiency. Drug release and pH responsiveness analysis demonstrates HNT-ZIF had lower release rate and both HNT-ZIF and ZIF were pH responsive. Additionally, SEM images show that gelatin hydrogel has too small pores and polymer layers. Moreover, swelling capacity of PLA embedded gelatin hydrogel was quite stable due to strong mechanical properties of PLA. The results of toxicity shows that HNT may contribute to increased cell viability in HNT-ZIF due to block the release of ions from organic linkers of ZIF. In high concentration of ZIF, cell viability was higher than followed decreased concentration with 1:2 dilution due to the fact that it was agglomerated. In lower concentration, especially 0.0025 mg/µL, there could be more released ZIF without agglomeration. Moreover, the incorporation of hydrogel nanocarrier composites significantly enhances cell viability compared to samples lacking hydrogels. This demonstrates that hydrogel effectively slows down the release of ions and drugs.