The development of pH-responsive microcapsules for controlled drug delivery has garnered significant attention. This study investigates the fabrication and characterization of microcapsules composed of different nanocomposites, focusing on their pH responsiveness for potential drug delivery applications. The research delves into the impact of pH and temperature on microcapsule morphology, stability, and drug release profiles, utilizing various microscopic, spectroscopic, and thermal analysis techniques.
Morphological and Stability Analysis of pH Responsive Microcapsules
Optical microscopy revealed interconnected microcapsules with robust mechanical stability, attributed to the non-covalent interactions between functionalized graphene sheets and the copolymer Poly(NIPAM-co-MAA). Hydrogen bonding between the amide and carboxylic acid groups of the copolymer and the functional groups on graphene facilitated stable microcapsule formation. Temperature increases led to a decrease in microcapsule diameter, suggesting potential for temperature-dependent drug release. Control experiments with polymethacrylic acid microcapsules demonstrated no diameter change with temperature variations, highlighting the unique thermoresponsive properties of the Poly(NIPAM-co-MAA)/GO microcapsules.
OPM images of microcapsules at 30°C (a) and 38°C (b). White arrows indicate shrinkage due to temperature.
Electron microscopy further elucidated the microcapsule morphology. FESEM images revealed surface roughness at pH 7.5 due to polymer agglomeration around graphene sheets. At the lower pH of 5.2, larger pore sizes were observed, likely due to weaker non-covalent interactions. HRTEM analysis showed a well-spread polymer layer on graphene sheets at pH 7.5, while at pH 5.2, the polymer formed stacked multiple sheets. The intact graphene sheets underscored their role in providing a stable microcapsule framework.
FESEM and HRTEM images of microcapsules at pH 7.5 (a, c) and pH 5.2 (b, d). White arrows indicate pores.
Drug Release Profiles: Influence of pH and Temperature
UV illumination studies revealed faster and greater drug release at pH 4 compared to pH 7, confirming the pH responsiveness of the microcapsules. Furthermore, drug release was enhanced at 40°C compared to 30°C at both pH levels. Fluorescence spectroscopy corroborated these findings, showing higher initial release efficiency at lower pH and higher temperature. Saturation in drug release was reached more rapidly under these conditions. DLS studies revealed a higher net negative charge on the polymer at pH 7, leading to stronger binding with GO and slower drug release compared to the lower acidic pH of 4.
pH and temperature-dependent drug release under UV light.
Atomic absorption spectroscopy (AAS) was employed to investigate the release of the anticancer drug cisplatin. Higher cisplatin release was observed at pH 4. Temperature-dependent studies showed increased release at 40°C compared to 30°C, particularly at pH 4. Fluorescence microscopy confirmed these results, with minimal fluorescence observed at pH 7 (indicating encapsulated riboflavin) and noticeable fluorescence at pH 4, demonstrating rapid riboflavin release in the acidic environment.
Fluorescence microscopy images of riboflavin release at pH 7 (a) and pH 4 (b).
Biocompatibility and Characterization of Microcapsule Components
MTT assays demonstrated the biocompatibility of the polymer solution, with over 80% cell viability up to a concentration of 1.8%. This finding supports the potential use of these microcapsules for biomedical applications. Further characterization was performed using various techniques. 1H NMR spectroscopy confirmed successful polymerization. FTIR spectroscopy revealed the presence of functional groups and their interactions within the nanocomposite. TGA analysis showed enhanced thermal stability of the microcapsules compared to the parent polymer, attributed to non-covalent interactions. DSC analysis determined the glass transition temperature and cloud point temperature of the copolymer. Raman spectroscopy confirmed the presence of GO and its interaction with the polymer in the microcapsules.
DSC thermogram of Poly(NIPAM-co-MAA).
Conclusion
This comparative study demonstrated the successful fabrication of pH-responsive microcapsules from different nanocomposites. The comprehensive analysis highlighted the significant influence of pH and temperature on microcapsule morphology, stability, and drug release kinetics. The findings underscore the potential of these microcapsules as promising candidates for controlled drug delivery systems, particularly in applications requiring targeted release in specific pH environments. Further research could explore the encapsulation and release of various therapeutic agents using these microcapsules for diverse biomedical applications.
