Nanoparticle impregnated self-supporting protein gel for enhanced reduction in oxidative stress: A molecular dynamics insight for lactoferrin-polyphenol interaction.

In the present work, lactoferrin (Lf) based nanoparticle incorporated self-supporting gel encapsulating a flavonoid, quercetin (Q), was developed. The complex formation between Lf and Q was assessed using molecular docking and dynamics simulation that lactoferrin and quercetin showed strong interaction and binding supporting hydrophobic interaction. The microscopic, spectroscopic, and x-ray techniques were used to characterize the gel extensively. In vitro drug release was studied to understand the release pattern of quercetin from the protein gel. The viscosity of the gel and its rheological characteristics were determined using a Brookfield viscometer. Ex vivo skin permeation studies using vertical diffusion cells were carried out to understand its skin permeation properties. The gel showed strong anti-oxidant activity using the DPPH scavenging assay. The enhanced effect of the Lf-Q complex on antioxidant enzyme activity (superoxide dismutase, catalase, and malondialdehyde), was supported by molecular dynamics, surface hydrophobicity, and in vitro studies. To investigate the effect of the gel on angiogenesis, the chorioallantoic membrane assay was performed and its compatibility with erythrocytes was also assessed. Suitability for topical administration was assessed using skin irritation studies performed on Sprague Dawley rats. The overall results suggest that the developed NiPG is suitable for cutaneous localization of quercetin with enhanced antioxidant activity.

ZIF-8 nano confined protein-titanocene complex core-shell MOFs for efficient therapy of Neuroblastoma: Optimization, molecular dynamics and toxicity studies.

In the present study, we have developed the core-shell metal organic framework (MOF) of zinc, wherein titanocene dichloride (TC) loaded lactoferrin (Lf) functioned as a core. The complexation of TC to Lf was studies using molecular dynamics study, Quantum mechanical model and spectroscopic investigations. Plackett-Burman design was used to screen and select the critical factors affecting the responses (size, zeta potential and PDI) while the effect of those parameter on the quality attributes (size and yield) was studied by means of a Box-Behnken design. The optimised Lf-TC nanoparticles were loaded inside the ZIF-8 framework along with an anticancer agent 5 Fluorouracil and characterized using techniques like FTIR, PXRD, Raman spectroscopy, EDX and UV-NIR spectroscopy and morphological techniques like SEM, TEM, AFM. The compatibility of the loaded ZIF-8 framework was examined by haemocompatibility studies. The potential of developed nanoplatform against Neuroblastoma was assessed using a cell line studies along with in vivo toxicity studies to ascertain its safety for after in-vivo administration in Wistar rats. Therefore, we can conclude that by employing the approach of DOE we were able to optimize the size and yield of Lf-TC NPs and further by loading inside ZIF-8 framework along with an anticancer drug like 5 fluorouracil we were able to develop a potential nanoplatform for the multimodal therapy of Neuroblastoma.

Hyaluronic acid-drug conjugate modified core-shell MOFs as pH responsive nanoplatform for multimodal therapy of glioblastoma.

Multimodal therapeutic approach has been gaining lot of attention for effective therapy of cancer. In the present work, a novel and unique pH responsive nanoplatform have been developed for multimodal therapy of glioblastoma using protein, biopolymer and MOFs. Lactoferrin (Lf) has been used as protein matrix for loading titanocene which was then enclosed in ZIF-8 framework along with 5-FU (ZIF-8@Lf-TC). The ZIF-8 was further coated with Lenalidomide-HA conjugate linked via hydrazone linkage (LND-HA@ZIF-8@Lf-TC). The developed nanocomposite was extensively characterized using spectroscopic, x-ray and electron microscopic techniques. The nanocomposites were evaluated for pH responsive drug release, stability, bio-interaction, and haemocompatibility which confirmed pH responsive nature of nanocomposite, stability and absence of any significant interaction with biomolecules. In obtained results for in vitro cell line studies performed in U87MG and RAW264.7 cells demonstrated enhanced cell cytotoxicity against cancer cells which was further supported by results of cellular ROS generation and surface ROS generation by nanocomposites. The Zinc and Lf mediated disruption of intracellular IL-6 and TNFα levels was observed with synthesized nanocomposites. They demonstrated pH responsive release of 5-FU and LND along with sustained release of both drugs in simulated medium. The LND-HA@ZIF-8@Lf-TC demonstrated superior cell growth supressing ability compared to ZIF-8@Lf-TC and ZIF-8. The nanocomposites were stable in biomimicking environment as well as did not show any significant interaction with RBC, plasma or CSF. The overall results suggest that LND-HA@ZIF-8@Lf-TC can be explored as promising platform for dual drug delivery mediated multimodal therapy of cancer.