The leading living bacteria formulations currently available are from a limited list of genera and are generally limited to gastrointestinal tract syndromes. A formulation composed of living Bacillus subtilis incorporated in a thermoresponsive hydrogel that hardens after administration on the skin and continuously produces antifungal agents is described. The ability of the formula to support bacteria growth and its mechanical properties and penetrability through the skin are fine-tuned by varying the ratio between polymer concentrations and bacterial media. The formula penetrates via the stratum corneum and accumulates in the epidermis without penetrating the inner, dermis layer. In vivo results mirror the results seen in vitro: bacillus formulations completely inhibit candida growth, demonstrating clinical effects comparable to those achieved by ketoconazole. LC-MS/MS analysis of the bacterial formulation confirms the presence of surfactin, the most powerful biosurfactant that possesses a broad antifungal activity. This platform may enable rational design of novel formulations composed of secreting bacteria inside a responsive, smart, hydrogel-which is the prerequisite for producing a successful drug delivery system.
Surgical sealants are widely used to prevent seepage of fluids and liquids, promote hemostasis, and close incisions. Despite the remarkable progress the field of biomaterials has undergone, the clinical uses of surgical sealants are limited because of their short persistence time in vivo, toxicity, and high production costs. Here, the development of two complementary neat (solvent-free) prepolymers, PEG 4 -PLGA-NHS and PEG 4 -NH 2 , that harden upon mixing to yield an elastic biodegradable sealant is presented. The mechanical and rheological properties and cross-linking rate can be controlled by varying the ratio between the two prepolymers. The tested sealants show a longer persistence time compared with fibrin glue, minimal cytotoxicity in vitro, and excellent biocompatibility in vivo. The neat, multiarmed approach demonstrated here improves the mechanical and biocompatibility properties and provides a promising tissue sealant solution for wound closure in future surgical procedures.
Particulate systems are widely used in biomedical applications, yet current systems are limited by their stability, complicated production processes, and the use of toxic excipients and cosolvents. Here, a new concept for an injectable nanocarrier system based on the in situ self‐assembled star polyethylene glycol (PEG)– poly(lactic‐co‐glycolic acid) (PLGA)/drug mixture is presented. The new injectable material is based on a neat (solvent‐free) liquid copolymer that self‐assembles after it is injected along with the drug to form a particulate delivery system. The nanocarriers’ formation rate and encapsulation capabilities of hydrophobic drugs can be fine‐tuned by changing the molecular weight of the PLGA segment. Furthermore, the starPEG–PLGA‐based system demonstrates potential as a drug carrier for hydrophobic drugs and shows biocompatibility with cell line culture.
The mechanical properties of polylactic acid (PLA), largely determined by its molecular weight and tacticity, can be modified by copolymerization and multi-armed structure, among other things. A series of liquid PEG 4 -PLA copolymers bearing various PDLLA or PLLA of increasing molecular weights was synthesized and characterized.The glass transition temperature and viscosity gradually increased with the molecular weight and the optical purity of the copolymer's PLA segment. The release profiles of two model drugs, bupivacaine HCl and bovine serum albumin were comparable, and controlled by the molecular weight and dissolution of the polymeric carrier. These findings can help in the development of new applications in biomedicine in which viscosity plays a significant role.
In article number https://doi.org/10.1002/adfm.201801581, Boaz Mizrahi and co‐workers report an anti‐fungal delivery system based on secreting bacteria inside a thermo‐responsive hydrogel. The formula hardens after administration whereas bacteria continuously produce antifungal agents and deliver them in situ. This system could provide an efficient and safe alternative to traditional fungal infection treatments.
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