br Fig Isotherm and pore distribution curves of a
Fig. 8. Isotherm and pore distribution curves of a) [email protected] and b) [email protected]@L-Dopa based on the BET and BJH method, respectively.
Finally, the forth mass loss step in temperature above 570 °C is probably due to the decomposition of the mixed metal oxide into a spinel phase .
Also, according to the obtained results from ICP-AES measurements, the drug carrier being exposed to diﬀerent pHs, it was determined that the composition of [email protected] remains unchanged.
Zeta potentials of [email protected] and [email protected]@L-Dopa in the
dispersion are positive and the average zeta potentials given by the instrument are 41 and 16 mV for [email protected] and [email protected]@L-Dopa respectively. The positive zeta potential of the LDH structures is in principle attributed to the structural positive charge and the electric double layer on the LDH surface. Although the interior charges of LDHs are fully screened by the interlayer anions, the surface structural charges are not fully balanced by the adsorbed surface anions because the surface-adsorbed anions can desert the electric double layer
on the surface of LDHs, and thus the LDH particles have a surface po-sitive charge. After placing a part of L-Dopa inside the layers and on the surface of [email protected], the negative charge on the surface in-creases which cause smaller zeta potential in [email protected][email protected] (Fig. 11a).
In order to investigate the size of [email protected]@L-Dopa, size distribution analysis was performed using dynamic light scattering (DLS) in aqueous solution. It was found that the average size of [email protected]@L-Dopa was about 150 nm. Fig. 11b shows that the particles range in size from 70 to 400 nm and possess an average size of 150 nm. According to the obtained results from TEM images, [email protected]@L-Dopa has uniform and spherical morphology and the mean diameter of the particles are about 130 nm (Fig. 5). The main reason of diﬀerence between particle size derived from TEM analysis and DLS data is aggregation of [email protected]@L-Dopa nanoparticle.
3.2. pH-dependent L-Dopa loading and release from [email protected]
In order to optimize the loading of L-Dopa on the [email protected] structure and evaluation of the drug solubility in diﬀerent body en-vironments (normal and cancerous cells), the synthesis of [email protected]@L-Dopa was investigated in two diﬀerent pHs. As it appears from the Fig. 12, the amount of drug loading and drug encapsulation eﬃ-ciency in pH = 7.4 are higher than pH = 5.5.
The L-Dopa molecules interact with the LDH layers principally via electrostatic, Methoctramine and van der Waal's forces. Therefore, having a higher negative charge of interlayer drug, play an important role in the replacement of L-Dopa in the CaAl-LDH structures. Also, increasing the pH causes enhancing the hydrogen bond strength be-tween L-Dopa and CaAl-LDH and facilitates the anion exchange process. Therefore, formation of hydrogen bond between L-Dopa and CaAl-LDH cause increases the amount of drug in the [email protected]@L-Dopa structure.
The increment of the loading of L-Dopa on [email protected] in the pH = 7.4 (52 wt%), clearly demonstrates the higher solubility and re-lease of the drug in cancerous cells which have a lower pHs than normal cells. It is notable that, the lower solubility of L-Dopa at pH = 7.4, justifies the greater amount of drug encapsulation eﬃciency and drug content (Fig. 13).
In the next step of our investigation, the drug loading studies were carried out at constant pH = 7.4 by varying the concentration of L-
Dopa. As illustrated in Table 1, the adsorption of L-Dopa on the [email protected] was much higher than Fe3O4. Strengthening the hydrogen bonds of L-Dopa-carrier and increasing the surface area of the carrier are the main reasons for the increment of drug loading and drug encapsulation eﬃciency. It is noteworthy that, the amount of L-Dopa
Fig. 11. a) Zeta potential distribution of [email protected] and [email protected]@L-Dopa, b) DLS particle size analysis of [email protected]
Fig. 13. Reducing the hydrogen bond strength with decreasing pH.
Table 1 Optimization of the drug loading and drug encapsulation eﬃciency of L-Dopa.
Entry Carrier Drug/ Drug Drug encapsulation
loading increased from 36% to 52% with increasing the weight ratio of L-Dopa to carrier from 1 to 1.5. Further increase in the weight ratio of L-Dopa to [email protected] showed no enhancement in the drug loading and drug encapsulation eﬃciency (Table 1, entry 4). The drug release behaviour of [email protected]@L-Dopa was in-vestigated in phosphate buﬀer (pH = 7.4) and acetate buﬀer (pH = 5.4). As mentioned previously, the release profile of L-Dopa is aﬀected by pH changes. The extracellular pH of cancerous tissues are often acidic  and release features of [email protected]@L-Dopa at pH = 5.5 was investigated to simulate the behaviour of the drug de-livery systems in the natural physiological environment of the tumor cells [35,36]. The L-Dopa loaded [email protected] with a drug loading of 52% showed the release profile attributed to the pH of the media (Fig. 14). At higher pHs (pH = 7.4), the obvious decrease in the L-