Complexes of cationic liposomes with DNA have emerged as promising nonviral vectors for delivering genetic information into cells for gene therapy. Kinetics of the liposome/DNA complex (lipoplex) formation on a millisecond time scale are studied by monitoring time evolution of fluorescence of 8-anilino-1-naphthalene sulfonic acid (ANS) and ethidium bromide (EtBr) in a continuous flow microfluidic channel coupled to a fluorescence microscope. The formation of lipoplexes between calf thymus DNA and liposomes based on two novel cationic lipids (Lip1810 and Lip1814) are found to follow a two-step process with kinetic constants for the Lip1814/DNA complex (k1 = 1120-1383 s-1, k2 = 0.227-1.45 s-1) being significantly different from those (k1 = 68.53-98.5 s-1, k2 = 32.3-60.19 s-1) corresponding to formation of the Lip1810/DNA complex. The kinetic pathway leading to the formation of Lip1814/DNA complex is diffusion-controlled whereas the formation of Lip1810/DNA complex occurs by a conformational rearrangement-controlled pathway. The observed difference in the kinetics of lipoplex formation likely originates from different structures of the lipid/DNA complexes.

To realize a customizable biogenic delivery platform, herein we propose combining cell-derived extracellular vesicles (EVs) derived from breast cancer cell line MCF-7 with synthetic cationic liposomes using a fusogenic agent, polyethylene glycol (PEG). We performed a fluorescence resonance energy transfer (FRET)-based lipid-mixing assay with varying PEG 1000 concentrations (0%, 15%, and 30%) correlated with flow cytometry-based analysis and supported by dimensional analysis by dynamic light scattering (DLS), transmission electron microscopy (TEM), and atomic force microscopy (AFM) to validate our fusion strategy. Our data revealed that these hybrid vesicles at a particular concentration of PEG (∼15%) improved the cellular delivery efficiency of a model siRNA molecule to the EV parental breast cancer cells, MCF-7, by factors of 2 and 4 compared to the loaded liposome and EV precursors, respectively. The critical rigidity/pliability balance of the hybrid systems fused by PEG seems to be playing a pivotal role in improving their delivery capability. This approach can provide clinically viable delivery solutions using EVs.

Since their inception, biomaterial-based systems have played a central role in various biomedical applications. However, there are still gaps in knowledge about their in vivo fate which limits their applications. Understanding these gaps is the key to developing next generation materials that are easy to translate to a clinical setting. In this chapter, we will discuss a few examples of widely used nanocarriers (NCs) with known immune interactions and clearance, and their success in preclinical and clinical models. We will further discuss certain barriers to translation and how to overcome them.

Molecular hydrogels represent a fascinating area of research that has its roots in drug delivery. However, now molecular hydrogels play an intrinsic role in a multitude of applications in various fields of biomedical research such as bioengineering, immunotherapy, tissue adhesives and sealants, cell growth matrices, and stimuli-responsive materials. The design of new biomaterials that can release cargo depending on multiple stimuli and their capacity to hold vast amounts of cargo has significantly expanded their use. However, their clinical translation is still dependent on their intrinsic design and is governed by multiple factors such as easy clearance, lack of immune response, and breakdown into nontoxic products. This chapter describes a few accounts of a new class of molecular hydrogels with their potential applications through preclinical models.

Herein we report the covalent grafting of chitosan on graphene oxide (GO) followed by a simple approach for anchoring silver (AgNPs) and gold (AuNPs) nanoparticles onto a chitosan grafted graphene oxide surface by a NaBH4 reduction method. Catalytic activity of prepared heterogeneous GO grafted chitosan stabilized silver and gold nanocatalysts (GO-Chit-Ag/AuNPs) was explored for the reduction of aromatic nitroarenes and degradation of hazardous azo dyes in the presence of NaBH4. Both catalysts were found to exhibit excellent catalytic activity towards the reduction of aromatic nitroarenes and azo dyes degradation. Furthermore, the nanocatalysts were found to be selective towards the reduction of nitro groups in halonitroarenes without any dehalogenation under mild conditions.