The fragment peak of the mass spectroscopy 135 [679-543] and 39[1030-991] polymer, which reflects the fragment of potassium sulfate and K+ ion present.
1. Process of Gel Formation through de-solvation.
The solubility and conformational study were performed in our laboratory, which suggests that the carrageenan behaves differently in cold water and nano water because of the conformational change from 1C4 helix to 4C1coilform. [18] It was utilized to create the nano gel; it was demonstrated that the solution needs be heated in order for it to convert to its matching disoriented form and remain suspended, compared to cold water. The carrageenan prefers to be in a lower energy state conformer and forms the gel with the helical conformation. (Figure 2). Conformation is an important aspect in macromolecular gels because it controls the three-dimensional structure and interactions inside the gel matrix. The gel's mechanical strength, responsiveness to external stimuli, and ability to encapsulate or release substances can all be affected by the conformation of the gel's components.[19]
In cold water, it forms a gel, and in hot water, the carrageenan gets solubilized and remains in the disoriented form, which does not allow it to form a gel and remain in the solution phase. It is also well established that the K+ or any ion influences the formation of the gel as seen below given figure 3. [20]
Later, the carrageenan solution in hot water was treated with methanol dropwise, and the cloudy mixture began to form, allowing the polymer to be de-solvated (Figure 4); additionally, the pH analysis of the process cried out to see the influence of H+, but the H+ remained stable and its involvement was eliminated from the possibility of making the nanoparticle. The solution's de-solvation triggered the creation of the nanocluster and the vicinity of the all-disoriented coil conformation. [21] However, the drop in temperature causes the conformation to be in the oriented form and initiates the nanoparticle with an excess of water, as confirmed by the IR analysis of the nano and regular gel SEM image below with detail description.
2) Evaluation of the Gels:
A) Infra-Red Interpretation:
The experimental study below was also corelated to the comparison study of the nanogel and simple gel using IR spectroscopy, which shows clearly the broad differences between the two. The two-four major parts of the carrageenan's characteristic parts represent the entirety of the change in the compound's nano (Fig. 5) and simple gel form (Fig 6)
a) Area A: The region-coloured red indicates O-H stretching at 3000 cm-1, which reveals details about the water's molecular structure and intramolecular interactions. The nano-formulation showed a peak with a high wave number and intensity, indicating a higher water content and intramolecular interaction. [22]
b) Area B: The higher wave number and intensity in the nano phase (2051 cm-1 >2039 cm-1) compared to the macro phase provides further evidence that the nano formulation has a higher concentration of free ions, a finding that is corroborated by the conductivity test. [23] The nanogel has higher conductivity (as shown in table 5) than simple gel because it generates molecular networking, which functions as an electric contact between the molecules, and it also has more water, which displays high conductivity behavior. It can also be based on the creation of conductive pathways in the bulk of a composite network via nanoparticles create relationships. [24-25] The relationship between high conductivity of a gel and medication application might be significant, especially in the context of transdermal drug delivery systems. Conductive gels are commonly employed as medication carriers in medicinal and cosmetic purposes.
Table 5: Conductivity evaluation of simple and nanogel
c) Area C: The bonded water content and OH bending in the formulation, with intermolecular interaction, are represented by the area of 1644 cm-1. We found that the nano gel had a peak absorption of 86%, while the simple gel peaked at 73%, indicating that the nano gel contained more bonded water through strong intermolecular interaction. (Figure 7) [22] The figure below depicts the intramolecular and intermolecular interactions of water in the nano gel, as well as the free state of K+, which allows the nano gel to form at a smaller scale due to a greater driving force, it is also represented by the SEM image too. (Figure 8)
Nano Gel was examined by SEM an image to obtain the particle size by the verified lines provided in each image, and the particle was then studied via the measurement line and measurement circle. The final data was calculated in each case, and the particle means were determined to be around 160 nm, indicating that the particle in the gel network is nanoscale, as shown in table 2 and figure 8.
Table 2: Particle size distribution inside the nano gel
The final data was calculated in each example, and the particle mean was determined to be around 520 nm, indicating that the particle in the gel network is not prevalent in the nano material. The mean and distribution in table 3 and figure 9 are used for easy identification. The gel in this range will be considered as macrogel and have various limitation as compare to nano, like the encapsulated capability, targeted delivery and various others.
Table 3: Particle size distribution inside the gel
In addition, the nano with regular pattern surface compares favorably to the simple gel, whose surface displays discontinuity Furthermore, as shown in the side-by-side SEM image of both gels, the nano with the regular pattern surface is superior to the simple gel, whose surface has discontinuity. (Figure 10)
The confirmation of the nano particle inside the core of the nano gel, a clear sign of the gel's unusual properties, which were further examined with the usage on the drug delivery system. The surface feature also reveals its regular shape, which provides more regularity than typical gel.
d) Area D: The area represents the S-O---K+ bond and the case of the nano gel the high intensity of the S-O was observes, compare to simple gel, because the less interaction of the K+ with the O and no disturbance in the bond strength, however in the case with the S-O bond strength in the simple was observed similar due the more attraction it remains stable and dipole moment was high with nano gel with high intensity of the area peak. (Figure 11) The more interaction with K+, it also justifies with the freer K+ ion in the case of nano gel. [26]
The more content of water represents the degree of freedom of water molecules and more movability, which is related to gel strength and flexibility, it was also observed during the calculation of the gel point. [27]
The gel point was calculated by examining the gel to solution property as well as critically analyzing the temperature with real-time data, as shown in the picture below. The gel point of the nano gel was 50 oC, whereas the normal gel had a gel point of 64 oC; additionally, the melting point of the nano gel was 48 oC, while the normal gel had a melting point of 62 oC (Figure 12). The difference between the gel points reveals both the difference and the elasticity of the gel. The lower the Gel point, the better the spreadability, which can be used for topical drug delivery method to release in the intended site. The IR was also justified by the lower gel point with high water content.
B) Special Characters and comparison of Simple and Nano Gel:
A major finding in the results obtained while comparing nano gel and simple gel of CG is fluorescently seen in nano gel, unlike simple gel; additionally, in the B with indirect fluorescent light, the blue spot was visible; however, the normal gel remains transparent. (Figure 13)
According to scientific thinking, the reason for this is relatively simple: once the particle gets equal in size to the wavelengths of light involved, quantum effects begin to matter for the particle's behavior. Based on this application, it may be anticipated that this can be used for a variety of reasons such as diagnostic as a dye and is biodegradable, making it preferable to others. [28]
Viscosity:
The viscosity of the nano gel was found as 252 centipoise and the simple gel has 649, (Table 4) which also justifies the water content in the nano gel is more and its sensitivity with temperature because of the more water content and heat transfer is more in the nano gel. The nano gel's low viscosity indicates its low adherent feature, which is a positive signal as a drug carrier for releasing drugs without obstructing them.
Table 4: Viscosity results of nano and simple gel
Spreadability:
The spreadability of nanogel and simple gel was computed using the above-mentioned approach, and it was discovered that nanogel has a high spreadability (Figure 13) by applying a specified force at the same time to obtain the spread area. The period was 5 minutes, and the covered area of the nano gel was calculated to be 1.2 cm diameter and 1cm for the gel, indicating a difference in both gels. The gel's strong spreadability supports its low viscosity and high-water content, indicating a higher value for the drug to be distributed via the topical route. Its temperature sensitivity will also give a synergistic impact in the drug's topical administration. (Figure B SI)
The higher the water content and the nano size of the particle, the greater the gel's spread ability, which may be very useful for topical application with a higher amount of the drug, [29] where the dissolution and absorption of the drug will be greater due to the higher solubility and lower viscosity with low tensile strength (Figure 14).