Cyclodextrins (CD) are a group of cyclic oligosaccharides with a cavity/specific structure that enables to form inclusion complexes (IC) with a variety of molecules through non-covalent host-guest interactions. By an elegant combination of CD with biocompatible, synthetic and natural polymers, different types of universal drug delivery systems with dynamic/reversible properties have been generated. This review presents the design of nano- and micro-carriers, hydrogels, and fibres based on the polymer/CD supramolecular systems highlighting their possible biomedical applications. Application of the most prominent hydrophobic aliphatic polyesters that exhibit biodegradability, represented by polylactide and polycaprolactone, is described first. Subsequently, particular attention is focused on materials obtained from hydrophilic polyethylene oxide. Moreover, examples are also presented for grafting of CD on polysaccharides. In summary, we show the application of host-guest interactions in multi-component functional biomaterials for controlled drug delivery.
1 May 2021 in Colloids and Surfaces B: Biointerfaces
Lung cancer is the leading cause of cancer death because of smoking and air pollution. Therefore, new ideas should be provided for lung cancer treatment in which the delivery of anticancer drugs to the local tumor site can be achieved. For this purpose, we propose the use of stereocomplexed spherical microspheres with sizes between 0.5 and 10 μm loaded with doxorubicin (DOX) to be administered through the nasal route. In order to gain control over the microsphere morphology, size, and drug loading capacity, we systematically studied the influence of the solvent used for preparation and the functionalization of their building blocks, namely poly-l-lactide (PLLA) and poly-d-lactide (PDLA) with blocked or unblocked l-proline moieties. We could demonstrate that DOX release is generally determined by the size of the microspheres. The antiproliferative activity of DOX released from the different microspheres was shown in vitro using the A549 lung cancer cell line as a model. Moreover, when in direct contact to the cancer cells, smaller microspheres were uptaken and could serve as a reservoir for local drug release. Our findings not only provide a novel strategy to prepare PLA microspheres with controllable morphology and release of anti-cancer drugs but also offer additional possibilities for the application of stereocomplexed particles in anticancer therapy, with suitable sizes for nasal administration.
This article demonstrates that ionizing radiation induces simultaneous crosslinking and scission in poly(trimethylene carbonate-co-d-lactide) diblock and random copolymers. Copolymer films were electron-beam (EB) irradiated up to 300 kGy under anaerobic conditions and subsequently examined by evaluation of their structure (FT-IR, NMR), molecular weight, intrinsic viscosities, and thermal properties. Radiation chemistry of the copolymers is strongly influenced by the content of ester linkages of the lactide component. At low lactide content, crosslinking reaction is the dominant one; however, as the lactide ratio increases, the ester linkages scission becomes more competent and exceeds the crosslinking. Electron paramagnetic resonance (EPR) measurements indicate that higher content of amorphous carbonate units in copolymers leads to a reduction in free radical yield and faster radical decay as compared to lactide-rich compositions. The domination of scission of ester bonds was confirmed by identifying the radiolytically produced alkoxyl and acetyl radicals, the latter being more stable due to its conjugated structure.