Antibacterial Creams Containing Cationic Carbosilane Dendrimers for Wound Treatment

Abstract

Skin wounds are an important factor in developing bacterial infection, especially for chronic wounds. In this case, the exposure to long traditional antibacterial-based treatments can lead to the appearance of resistance to these drugs. This situation makes the search for alternatives to attack these infections essential, as it is the use of cationic multivalent systems. Here, we discussed the antibacterial and biological properties of different cationic carbosilane (CBS) dendrimers against () and () as models of Gram-positive and Gram-negative bacteria, respectively. Dendrimers are a type of multivalent molecule with a well-defined structure. The CBS dendrimers used in this work differ in several modifications that affect the hydrophobic/hydrophilic balance, which is very relevant to achieve bactericidal activity. These structural changes are the position of a short alkyl chain, in the internal dendritic structure or on the outer ammonium groups, the presence of a polyethylene glycol (PEG) chain instead of a cationic function, or in the vicinal moieties of the cationic functions, sulfur atoms or sulfone units. The studies allowed the selection of some dendrimers, all of them with the inner long chain and trimethylammonium (-NMe₃ ⁺) groups, as active ingredients of a topical cream (water in oil, W/O). The antibacterial and biological properties of the creams were also tested against bacteria because it is the most common pathogen involved in skin infections. We observed different abilities of the dendrimers to be released from the cream, depending on the dendrimer structure, and as a consequence, different antibacterial properties of the creams. Finally, an analysis of the physicochemical properties of the best formulation was also done.

Keywords: antibacterial; carbosilane dendrimer; quaternary ammonium; skin wound; topical cream.

1. Synthesis of Cationic CBS Dendrimers with Different Alkyl Ammonium Groups and Drawing of the Structure of Dendrimers 1a–c

1

Drawing of the structure of cationic CBS dendrimers with a longer internal alkyl chain 2 a–e.

2. Synthesis of the Cationic CBS Dendrimer with Sulfone Moieties 2e

2

Determination of the percentage cell viability by means of the alamarBlue method. Graph represents the mean ± SEM of the different groups. Legends: * 2b vs control (p < 0.05); **** 2e vs control (p < 0.0001).

3

Light microscopy micrographs (100x, scales 100 μm) of cultured fibroblasts following a 24 h incubation under exposure to the CBS dendrimers 2a–e at concentration equivalent to MBC recorded for (all) and (2e).

4

Rheological characterization. Storage (G′) and loss (G″) moduli in amplitude sweeps at 35 °C, with 1.6 Hz for the placebo cream (A) and cream 2a (B). Storage (G′) and loss (G″) moduli in frequency sweeps at 35 °C with oscillatory strain 0.1%, for cream placebo (C) and cream 2a (D). Flow characterization of creams placebo and 2a: (E) viscosity, η; (F) shear stress, σ.

5

Bacterial growth of bacteria (MRSA) in MH broth after incubation with the creams 2a, 2b, and 2e at 37 °C for 24 h (top) and 6 months (bottom, only cream 2a). In black, the absorbance of bacteria culture without treatment (positive control); in red, study group (cream), absorbance of bacteria culture after treatment with cream; in white, absorbance of only bacteria culture after treatment with cream (real activity, red minus blue); and in blue, absorbance of cream (negative control).

6

Agar-diffusion assays with topical biocide creams 2a, 2b, and 2e in and MRSA (after 24 h). N-A: Non-antibacterial. Area of inhibition is in cm².