Diabetes mellitus, an incurable metabolic disease, is characterized by changes in the homeostasis of blood sugar levels, being the subcutaneous injection of insulin the first line treatment. This administration route is however associated with limited patient’s compliance, due to the risk of pain, discomfort and local infection. Nanoparticles have been proposed as insulin carriers to make possible the administration of the peptide via friendlier pathways without the need of injection, i.e., via oral or nasal routes. Nanoparticles stand for particles in the nanometer range that can be obtained from different materials (e.g., polysaccharides, synthetic polymers, lipid) and are commonly used with the aim to improve the physicochemical stability of the loaded drug and thereby its bioavailability. This review discusses the use of different types of nanoparticles (e.g., polymeric and lipid nanoparticles, liposomes, dendrimers, niosomes, micelles, nanoemulsions and also drug nanosuspensions) for improved delivery of different oral hypoglycemic agents in comparison to conventional therapies.

The development of biotechnological protocols based on cationic surfactants is a modern trend focusing on the fabrication of antimicrobial and bioimaging agents, supramolecular catalysts, stabilizers of nanoparticles, and especially drug and gene nanocarriers. The main emphasis given to the design of novel ecologically friendly and biocompatible cationic surfactants makes it possible to avoid the drawbacks of nanoformulations preventing their entry to clinical trials. To solve the problem of toxicity various ways are proposed, including the use of mixed composition with nontoxic nonionic surfactants and/or hydrotropic agents, design of amphiphilic compounds bearing natural or cleavable fragments. Essential advantages of cationic surfactants are the structural diversity of their head groups allowing of chemical modification and introduction of desirable moiety to answer the green chemistry criteria. The latter can be exemplified by the design of novel families of ecological friendly cleavable surfactants, with improved biodegradability, amphiphiles with natural fragments, and geminis with low aggregation threshold. Importantly, the development of amphiphilic nanocarriers for drug delivery allows understanding the correlation between the chemical structure of surfactants, their aggregation behavior, and their functional activity. This review focuses on several aspects related to the synthesis of innovative cationic surfactants and their broad biological applications including antimicrobial activity, solubilization of hydrophobic drugs, complexation with DNA, and catalytic effect toward important biochemical reaction.

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The surface properties of nanoparticles have decisive influence on their interaction with biological barriers (i.e., living cells), being the concentration and type of surfactant factors to have into account. As a result of different molecular structure, charge, and degree of lipophilicity, different surfactants may interact differently with the cell membrane exhibiting different degrees of cytotoxicity. In this work, the cytotoxicity of two cationic solid lipid nanoparticles (SLNs), differing in the cationic lipids used as surfactants CTAB (cetyltrimethylammonium bromide) or DDAB (dimethyldioctadecylammonium bromide), referred as CTAB-SLNs and DDAB-SLNs, respectively, was assessed against five different human cell lines (Caco-2, HepG2, MCF-7, SV-80, and Y-79). Results showed that the cationic lipids used in SLN production highly influenced the cytotoxic profile of the particles, with CTAB-SLNs being highly cytotoxic even at low concentrations (IC50 < 10 µg/mL, expressed as CTAB amount). DDAB-SLNs produced much lower cytotoxicity, even at longer exposure time (IC50 from 284.06 ± 17.01 µg/mL (SV-80) to 869.88 ± 62.45 µg/mL (MCF-7), at 48 h). To the best of our knowledge, this is the first report that compares the cytotoxic profile of CTAB-SLNs and DDAB-SLNs based on the concentration and time of exposure, using different cell lines. In conclusion, the choice of the right surfactant for biological applications influences the biocompatibility of the nanoparticles. Regardless the type of drug delivery system, not only the cytotoxicity of the drug-loaded nanoparticles should be assessed, but also the blank (non-loaded) nanoparticles as their surface properties play a decisive role both in vitro and in vivo.