Drug molecules can interact with surfactant molecules either in their monomeric form, where the Benesi-Hildebrand equation determines the binding constant, or when a micellar pseudophase is formed, where the Kawamura equation assesses the partition coefficient. Benesi-Hildebrand plots represent the differential absorbance as a function of surfactant concentration below the critical micelle concentration (CMC), while Kawamura plots show this relationship above the CMC, where the drug can influence the CMC and needs consideration. This review aims to provide an overview of methods for evaluating drug-surfactant interactions in aqueous solutions, particularly below and above the CMC, using spectroscopic data. Understanding these interactions is crucial for pharmacodynamics, affecting drug binding, enzymatic activity, and formulation. Various surfactants were analyzed with diphenhydramine hydrochloride, levofloxacin, phenothiazine, moxifloxacin, and chlorpromazine hydrochloride to determine monomeric binding constants, while sulfathiazole, sodium valproate, cefotaxime, losartan, and metformin hydrochloride were assessed for partitioning coefficient values. Errors in Benesi-Hildebrand plots may arise from considering surfactant concentrations above the CMC, while mistakes in Kawamura plots may stem from neglecting to determine the CMC in the presence of drug molecules, which can alter the surfactant’s behavior.
In the current study, a core–shell inorganic nanostructure comprising a gold nanorod core and −mesoporous manganese dioxide shell was synthesized. Then, the mesoporous manganese dioxide shell was loaded with doxorubicin (DOX) and then coated with pluronic F127 and pluronic F127-folic acid conjugate (1.5:1 wt ratio of pluronic F127: pluronic F127-folic acid conjugate) to prepare targeted final platform. In this design, mesoporous manganese dioxide acted as a reservoir for DOX loading, anti-hypoxia, and MRI contrast agent, while the gold nanorod core acted as a photothermal and CT scan imaging agent. DOX was encapsulated in the mesoporous manganese dioxide shell with a loading capacity and loading efficiency of 19.8 % ± 0.2 and 99.0 % ± 0.9, respectively. The in vitro release experiment showed the impact of glutathione (GSH), mildly acidic pH, and laser irradiating toward accelerated stimuli-responsive DOX release. The ·OH production of the prepared platform was verified by methylene blue (MB) decomposition reaction. Furthermore, thermal imaging exhibited the ability of the prepared platform to convert the NIR irradiation to heat. In vitro cytotoxicity tests on the folate receptor-positive 4 T1 cell line revealed the remarkable cytotoxicity of the targeted formulation compared to the nontargeted formulation (statistically significant). The MTT experiment demonstrated that exposure to laser 808 irradiation enhanced cytotoxicity of the targeted formulation (p < 0.0001). The production of ROS in 4 T1 cells following treatment with the targeted formulation was demonstrated by the dichloro-dihydro-fluorescein diacetate (DCFH-DA) assay. Furthermore, in vivo investigations by implementing subcutaneous 4 T1 tumorized female BABL/c mice indicated that the prepared platform was an effective system in suppressing tumor growth by combining chemotherapy with PTT (photothermal therapy). Additionally, simultanous PTT and anti-hypoxic activity of this system showed potent tumor growth suppression impact. The percent of tumor size reduction in mice treated with FA-F127-DOX@Au-MnO2 + 808 nm laser compared to the control group was 99.7 %. The results of the biodistribution investigation showed tumor accumulation and modified pharmacokinetics of the targeted system. Lastly, 6 and 24 h post-intravenous injection, CT-scan and MR imagings capability of the prepared platform was verified in preclinical stage. The prepared multipurpose system introduces great opportunity to provide multiple treatment strategy along with multimodal imaging capability in a single platform for breast cancer treatment.
Aqueous suspensions of poorly soluble, crystalline drug particles in the sub-micron range hold the ability to regulate the drug release for a defined period of time after e.g., intramuscular, or subcutaneous administration, working as an eminent formulation strategy for the preparation of long-acting injectables. Aqueous suspensions are typically prepared by top-down approaches, e.g., wet bead media milling or high-pressure homogenization, containing the active pharmaceutical compound and surfactants and/or polymers for stabilization purposes. Currently, the screening of proper stabilizers and adequate stabilizer concentration during formulation investigations is based on a trial-and-error approach with variations in combinations, concentrations, and/or ratios. To obtain a more efficient methodology during formulation screening, the present study investigated the correlation between the surface activity of two different surfactants, i.e., poloxamer 188 and polysorbate 20, by drop profile tensiometry and Langmuir trough monolayer, and the obtained sizes of cinnarizine particles as a tool to predict the optimal surfactant concentration to prepare physical stable nano- and microsuspensions. The obtained results demonstrated that the molecular area determined as the area per surfactant molecule measured in the Langmuir trough combined with the specific surface area of the prepared suspensions could be used to predict the suitable concentration of the surfactant based upon short-term stress stability data. The results further showed that higher concentrations of poloxamer 188 were necessary to stabilize the suspensions when compared to the needed concentration of polysorbate 20. In addition, it was observed that there was a need for a slightly higher surfactant concentration when the suspensions were milled with the smallest bead size of 0.5 mm instead of larger sizes of bead (0.8 and 1.0 mm), which could not be accounted for by differences in specific surface area.