Conventional administration of drugs is limited by poor water solubility, low permeability, and mediocre targeting. Safe and effective delivery of drugs and therapeutic agents remains a challenge, especially for complex therapies, such as cancer treatment, pain management, heart failure medication, among several others. Thus, delivery systems designed to improve the pharmacokinetics of loaded molecules, and allowing controlled release and target specific delivery, have received considerable attention in recent years. The last two decades have seen a growing interest among scientists and the pharmaceutical industry in mesoporous silica nanoparticles (MSNs) as drug delivery systems (DDS). This interest is due to the unique physicochemical properties, including high loading capacity, excellent biocompatibility, and easy functionalization. In this review, we discuss the current state of the art related to the preparation of drug-loaded MSNs and their analysis, focusing on the newest advancements, and highlighting the advantages and disadvantages of different methods. Finally, we provide a concise outlook for the remaining challenges in the field.
New functionalized lactide copolymers containing acetal units were prepared for the first time in a controlled manner that enabled the regulation of the number of reactive groups introduced into the polyester chain. The presence of functional groups in the copolymer backbone provided chemical modification sites, and the nature of the acetal unit affected the material degradability. First, paraformaldehyde was reacted with selected diols containing reactive pendant groups (3-allyloxypropane-1,2-diol and 3-chloropropane-1,2-diol), which was catalyzed by p-toluenesulfonic acid, to synthesize new cyclic acetals with different functionalities (allyl- or chloro-). In addition, using butane-1,4-diol, a nonfunctionalized seven-membered cyclic acetal (dioxepane) was obtained for comparative studies. In the next step, the prepared cyclic acetals were used for cationic copolymerization with lactide in the presence of glycol as an initiator and triflic acid as a catalyst. Different temperatures (-15, 2, and 30 °C) and copolymerization times (24, 48, 72, and 192 h) were investigated to produce copolyesters with variable contents of acetal units in the range of 5-27%. The copolymers' structure and molar masses were carefully investigated using 1H, 13C NMR, 2D NMR, and size-exclusion chromatography. Moreover, the ability of functionalized copolymers to perform post modifications was also proven by the reaction with sodium azide and propanethiol. Finally, we speculate that structurally diverse groups can be attached to the copolyester chain, fine-tuning the on-demand properties, which could rapidly expand the library of polylactide-based materials.
In this study, porous networks were efficiently prepared by crosslinking hydrophilic poly(2-isopropenyl-2-oxazoline) (PiPOx) with dicarboxylic polyesters (HOOC–PLA–COOH or HOOC–PCL–COOH) in the presence of sodium chloride as a water-soluble porogen. Importantly, by using a relatively simple synthetic protocol, the resulting spongy materials were freely formed to the desired size and shape while maintaining stable dimensions. According to the SEM data, the porous 3D structure can be altered by the pore dimensions, which are dependent on the porogen crystal size. After porosity characterization, the mechanical properties were also evaluated via uniaxial compression and tensile tests. The porous networks formed hydrogels with a high water absorption capacity. Finally, after showing cytocompatibility by the MTT assay, we also demonstrated the applicability of the porous hydrogels as scaffolds for cell cultivation. The presented results suggest that this type of hydrogels is a promising material for tissue engineering.
This paper presents results of spectroscopic (NMR, FTIR, fluorescence), Q-TOF mass spectrometry and Z-potential analyses of interactions between octa(3-aminopropyl)silsesquioxane hydrochloride (POSS-NH2·HCl) and anticancer drug – doxorubicin hydrochloride. These studies aimed at explanation of the enhanced activity of doxorubicin on co-delivery with POSS-NH2. The results point to the formation of active complexes via ionic interactions between the ammonium chloride groups of silsesquioxane and the drug, and not, as suggested earlier, via NH⋯N hydrogen bonding. It has also been shown that the main driving force for the formation of the complexes can be strengthened by π–π stacking and hydrogen bonds. The experimental results are supported by quantum mechanical calculations. This work has proven that co-delivery with POSS offers a potentially advantageous and simple approach for improved efficacy in chemotherapy, avoiding often complicated synthesis of conjugates, involving covalent bonding between drug, nanocarrier and targeting agents.
The high photodynamic effect of the Newman strain of the S. aureus and of clinical strains of S. aureus MRSA 12673 and E. coli 12519 are observed for new cationic light-activated phenosafranin polyhedral oligomeric silsesquioxane (POSS) conjugates in vitro. Killing of bacteria was achieved at low concentrations of silsesquioxanes (0.38 µM) after light irradiation (λem. max = 522 nm, 10.6 mW/cm2) for 5 min. Water-soluble POSS-photosensitizers are synthesized by chemically coupling a phenosafranin dye (PSF) (3,7-diamino-5-phenylphenazine chloride) to an inorganic silsesquioxane cage activated by attachment of succinic anhydride rings. The chemical structure of conjugates is confirmed by 1H, 13C NMR, HRMS, IR, fluorescence spectroscopy and UV-VIS analyzes. The APDI and daunorubicin (DAU) synergy is investigated for POSSPSFDAU conjugates. Confocal microscopy experiments indicate a site of intracellular accumulation of the POSSPSF, whereas iBuPOSSPSF and POSSPSFDAU accumulate in the cell wall or cell membrane. Results from the TEM study show ruptured S. aureus cells with leaking cytosolic mass and distorted cells of E. coli. Bacterial cells are eradicated by ROS produced upon irradiation of the covalent conjugates that can kill the bacteria by destruction of cellular membranes, intracellular proteins and DNA through the oxidative damage of bacteria.