Optimization and In Vivo Toxicity Evaluation of G4.5 Pamam Dendrimer-Risperidone Complexes

Abstract

Risperidone is an approved antipsychotic drug belonging to the chemical class of benzisoxazole. This drug has low solubility in aqueous medium and poor bioavailability due to extensive first-pass metabolism and high protein binding (>90%). Since new strategies to improve efficient treatments are needed, we studied the efficiency of anionic G4.5 PAMAM dendrimers as nanocarriers for this therapeutic drug. To this end, we explored dendrimer-risperidone complexation dependence on solvent concentration, pH and molar relationship. The best dendrimer-risperidone incorporation (46 risperidone molecules per dendrimer) was achieved with a mixture of chloroform:methanol 50∶50 v/v solution pH 3. In addition, to explore the possible effects of this complex, in vivo studies were carried out in the zebrafish model. Changes in the development of dopaminergic neurons and motoneurons were studied using tyrosine hydroxylase and calretinin, respectively. Physiological changes were studied through histological sections stained with hematoxylin-eosin to observe possible morphological brain changes. The most significant changes were observed when larvae were treated with free risperidone, and no changes were observed when larvae were treated with the complex.

Preparation of self-assembled core–shell nano structure of conjugated generation 4.5 poly (amidoamine) dendrimer and monoclonal Anti-IL-6 antibody as bioimaging probe

“…When the molar ratio was further increased to 4:1, fractal growth of Table 1). The zeta potential of G4.5 dendrimers in deionized water was -56.5 ± 0.2 mV, which was in agreement with previous studies [23,31,32]. The antibody IL-6 is neutral in charge with zeta potential of -2.3 mV.…”

“…In addition, the spectrum contained bands corresponding to the bending and vibrational modes of amide NH at 1643 cm -1 and 3380 cm -1 respectively. After IL-6 conjugation, the latter amide NH band shifted from 3380 cm -1 to 3390 cm -1 [23] and the absorbance at 1460 cm -1 increased due to interaction between terminal carboxylate groups and IL-6 [26]. Two new absorbance appeared at 1250 and 1390 cm -1 , corresponding to stretching vibrations of the carbonyl groups.…”

“…A c c e p t e d M a n u s c r i p t well-defined polymer that has been widely used in drug delivery [23,24]. It has 128 surface carboxylate groups, which allows high degree of conjugation to targeting molecules such as IL-6 through EDC and NHS chemistry, as shown in Scheme 1. to C-H stretches within the dendrimer core.…”

Radiation‐Sensitive Dendrimer‐Based Drug Delivery System

“…After 2 h, the embryos were replaced with PBS in six‐well plates in the absence or presence of radiation, and images were captured at 1 dpi. Subsequently, the embryos were immersed in DOX‐loaded dendrimer derivatives and incubated for 48 h. Finally, images were captured again at 3 dpi73 and the intensity was calculated as follows$\mathrm{Intensity}\mathrm{ }\left(\%\right)\mathrm{=}\mathrm{\hspace{0.17em}}\frac{\mathrm{Fluorescence}\mathrm{\hspace{0.17em}}\mathrm{area}\mathrm{\hspace{0.17em}}\mathrm{of}\mathrm{\hspace{0.17em}}\left(3\mathrm{normal\hspace{0.17em}}\mathrm{normaldpi}-1\mathrm{normal\hspace{0.17em}}\mathrm{normaldpi}\right)}{\mathrm{Fluorescence}\mathrm{\hspace{0.17em}}\mathrm{area}\mathrm{\hspace{0.17em}}\mathrm{of}\mathrm{\hspace{0.17em}}1\mathrm{\hspace{0.17em}}\mathrm{dpi}}\mathrm{\hspace{0.17em}}\times \mathrm{\hspace{0.17em}}100\%$ …”

Synthesis of PAMAM dendrimer-based fast cross-linking hydrogel for biofabrication

“…[20] A merit of PAMAM dendrimers is that they can be cleared through kidney [21] which is important for hydrogels used in biofabrication. Due to their water solubility, non-immunogenicity, uniform structures, and ample active functional groups for chemical modifications, they have been extensively used for cancer targeting, [22,23] drug delivery, [24,25] gene delivery, [26,27] and imaging. [28,29] PAMAM dendrimers are also reported for hydrogel formation mainly for drug delivery purposes.…”