br Impact of intravenous diluent on the
3.6. Impact of intravenous diluent on the FNP properties
The final products of our study are lyophilized powders of α-man-gostin loaded FNPs for intravenous injection propose. Before injection, the powders need to be reconstituted in intravenous diluent such as dextrose 5% and NSS. Therefore, the stability of α-mangostin loaded FNPs in these two diluents was studied. After dispersion in NSS, all formulas showed particle aggregation with the surface charge of 0 mV in 2 h. However, in dextrose 5%, the particles were stable up to 24 h (Fig. 4A). This phenomenon could be explained by the diﬀerence in ionic strength between the two media. The NSS has an ionic strength of 0.15 M, whereas dextrose 5% is non-ionization nature. Based on the Derjaguin-Landau-Verwey-Overbeek (DLVO) theory, there are two main forces that control the interaction energy between two colloidal particles in a solution, including the attractive van der Waals force and the repulsive surface electrical force . Mathematically, this re-pulsive force originated from the electrical double layer interaction energy between two particles, which is dependent on the electrolyte concentration through the Debye constant κ (note that κ−1 is called the Debye length or the double layer thickness). Accordingly, an increase in solution ionic strength leads to an increase in the Debye constant, which in turn exponentially reduces the double layer energy, ultimately decreases the repulsive force . As a consequence, the FNPs get aggregate due to the Aprotinin of the attractive van der Waals force. Therefore, dextrose 5% is considered a suitable infusion medium for re-
In addition, the α-mangostin loaded FNPs dissolution profiles in dextrose 5% are also demonstrated in Fig. 4B. The drug release pattern was consistent between formulations, which followed the order of EDClow-FNP > PEI-FNP > EDChigh-FNP. These results were in agree-ment to the dissolution profiles in HEPES buﬀer. Within 24 h, 15–30% α-mangostin was released into the diluents, depending on the for-mulation.
Clinically, the long infusion time of up to 24 h (slow drug inflow rate) for chemotherapy is recommended to avoid hypersensitivity or allergic reactions caused by the immune system. However, such long hospitalization causes burdens in outpatient administration, increases administration costs, and reduces patient compliance . Hence, ef-forts should be made to increase the drug inflow rate as much as pos-sible, but slow enough to minimize unwanted reactions. Therefore, by utilizing fibroin to carry the cytotoxic drugs, a short infusion time is possible as the fibroin carrier could prevent the direct contact between the drugs and the immune system. Furthermore, within 3-h infusion, less than 10% α-mangostin released into the medium, thus, preserving the α-mangostin loaded FNPs eﬃcacy as a whole system.
3.7. Physicochemical stability
The physicochemical stability of lyophilized powders of α-man-gostin loaded FNPs were determined in terms of particle size, zeta po-tential, and the remaining drug, for a period of 6 months at 25 °C and 4 °C. At 25 °C, all formulas showed aggregation with a mean size of > 1 μm in only 1 month. Thus, further investigations were excluded. Nevertheless, at 4 °C, the FNPs size and zeta potential were maintained for at least 6 months. Temperature plays an important role in α-man-gostin loaded FNPs’ physical stability. At 25 °C, the kinetic energy of fibroin molecules in the particles, even in solid state, was higher than that at 4 °C. Hence, more inter- and intramolecular interactions were formed due to excessive contact, consequently, aggregation occurred. In term of chemical stability, > 99% of the α-mangostin retained in FNPs after 6 month storage at 4 °C, suggesting the suitability of the systems in protecting the entrapped drugs from degradation.