Enzymatically synthesized poly(δ-valerolactone) and poly(δ-valerolactone) nanohybrid usage in controlled drug delivery systems

Abstract

There is an increasing interest for the biopolymers these days, because oppose to synthetically/artificially formed ones, they are generated by renewable resources. It is clear that with the increasing population and the times when we need to pay more attention to the world's depleting resources, why the people are tending to use biopolymers instead of synthetic polymers, which are petroleum-based. In other words, with the developing technology, oppose to fossil resources, which are very traditional, people started to care to eliminate their carbon footprint. In order to make this valuable approach happen, they beginned to use natural resources. Due to their better biodegradability, reproducable, biocompatibility and chemical degradability, they indicate non-toxicity and they have low-weight. These qualities lead them to be used in not only packaging, textile, medical, agricultural industries, but also wearable devices, sensors and mostly in drug delivery systems. Due to their many benefits, including biocompatibility, nontoxicity, thermoplasticity, semi-crystalline and hydrophobic form, flexibility, along with controlled decomposition, PVL is an intriguing option and frequently utilized in biomedical implementations. PVL is a fundamental component in the production of anthracycline type of antibiotics and the controlled medications (like doxorubicin (DOX)), which are prescribed to avoid different types of cancer. Nanohybrid systems are composite substances constructed up of two or more different nanoscale constituents that are closely joined or blended at the molecular or atomic scale. When these elements are combined, a fresh substance with specific qualities that may be superior to those of the constituent parts individually can be produced. The resultant nanohybrids frequently show mutually beneficial impacts, which enhance efficiency across a range of applications. Having particle sizes varying from one to thousand µm in diameter, microspheres are a form of particle dispersion mechanism, where molecules of drug are incorporated in a polymer matrix by adsorption or dispersion. Numerous medical compounds, including peptides, proteins, nucleic acids and molecules of small size medicine could be encapsulated in microspheres and have the relevant therapeutic properties. The microspheres have garnered a lot of interest lately upon account of their tiny size of particles, unique surface features, and substantial surface-to-volume ratio. Chalcones are polyphenolic chemicals of various structures found in plants. There are several possible uses for chalcone-based compounds, including antibacterial, antiviral, antioxidant, anti-inflammatory, antidiabetic, antiulcer, anticancer properties. The remarkable chemical structure and intriguing pharmalogical properties of trans-chalcone (TC), also known as 1,3-diphenyl-2-propen-1-one, make it a prominent focus of scientific investigation alongside other chalcones. In this study, physical adsorption was employed in the first part to immobilize lipase on surface-modified rice husk ash (RHA) to be used in enzymatic ring opening polymerization. The silica based material underwent surface modification when amine groups were added to its surface by utilizing 3-aminopropyltriethoxysilane (3-APTES). Then, pysical adsorption methodology was used to immobilize the free form of Candida antarctica lipase B. By using the monomer ratios from prior study, poly(δ-valerolactone) and poly(δ-valerolactone) nanohybrid were generated by enzymatic ring opening polymerization. The reactions are conducted at 80oC for 24 hours to get the highest molecular mass for both polymer and nanohybrid. These resultant materials were ultimately found to be applied in the fabrication of microspheres. As following, the methodology of O/W emulsion was employed to fabricate TC-loaded PVL microspheres, TC-loaded PVL nanohybrid microspheres, drug-free PVL microspheres and drug free PVL nanohybrid microspheres. Afterwards, drug release mechanism of these fabricated microspheres were investigated. For this investigation, with three different PVA concentrations (0.1, 0.5, 1 (w/v)% ), there different TC:PVL ratio (10, 20, 40%) and TC:PVL nanohybrid ratio (10, 20, 40%) have been evaluated in order to ascertain greatest encapsulation efficiency, and thereby drug release profile. To define the thermal, chemical and mechanical properties, TGA, DSC, SEM and XRD were applied to these microspheres. The greatest encapsulation efficiencies were observed with specimen A-2 (1% PVA and 20% ratio of TC:PVL) as 98.6 ± 8.4 (%) and specimen C-2 (1% PVA and 20% ratio of TC:PVL nanohybrid) as 82.7 ± 6.4 (%). This research, also demonstrates that drug release mechanisms are not affected majorly by the pH-changes. The DSC analysis shows that addition of TC into microspheres has lowered the melting points but there were no any extra TC-peak on the curves, so it is concluded that TC is successfully encapsulated and molecularly dispersed into PVL and PVL nanohybrid microspheres. TGA analyses were used to compare the thermal degradation pattern of drug-free and TC-loaded PVL microspheres with PVL. Additionally, TGA analyses were used to compare the thermal degradation pattern of drug-free and TC-loaded PVL nanohybrid microspheres with PVL nanohybrid. Decompositions and weight losses have been evaluated and interpreted based on the scientific literature and the analyses that were conducted. The chemical groups that indicate the existence of TC, PVL, TC-loaded PVL microspheres, drug-free PVL microspheres, PVL nanohybrid, TC-loaded PVL nanohybrid microspheres, and drug-free PVL nanohybrid microspheres were all observed by using FT-IR as characterization technique. Since FT-IR spectras are alike, it shows that TC was determined to be encapsulated within the microspheres. XRD analyses were used besides to several other characterizations to investigate the impact of TC loading on the crystalline structures and the crystallinity of microspheres. The SEM images reveal that every single one of the microsphere formulations had spherical shape. To observe the drug release behaviour of the microspheres fabricated in various surroundings, pH-dependent drug release investigations were conducted in the present research by employing two pH levels that were 5.6 and 7.4. The total cumulative release of TC was enhanced by the PVL microsphere formulations, reaching 42.1% in pH 7.4 ambient and 43.5% in pH 5.6 ambient. Moreover, the total cumulative release of TC was enhanced by the PVL nanohybrid microsphere formulations, reaching 39.4% in pH 7.4 ambient and 34.2% in pH 5.6 ambient. The TC release was conducted for an overall duration of 744 hours in each case. Finally, the release kinetics were examined. The release was found to be compatible with the kinetic model of Korsmeyer-Peppas. All microsphere formulations had TC release that was controlled by Fickian diffusion, according to the calculated n value. In conclusion, the goal of this study is to develop new controlled drug delivery systems by integrating a transchalcone into biological in origin polymeric carriers. A biocompatible, environmentally friendly, high-molecular-weight polymer and nanohybrid containing home-made immobilized enzymes that are compatible for human body will be produced in order to fabricate microspheres. Transchalcone will be incorporated with the polymer and nanohybrid generated by biocatalyst for use in therapy. Following the completion of all characterization tests and investigation of drug release profiles, it can be clearly said that this research's findings suggest that PVL microspheres or PVL nanohybrid microspheres may find implementation in prolonged therapeutic applications.