Dataset Information

"Smart" Polylactic Acid Films with Ceftriaxone Loaded Microchamber Arrays for Personalized Antibiotic Therapy.

ABSTRACT: Bacterial infections are a severe medical problem, especially in traumatology, orthopedics, and surgery. The local use of antibiotics-elution materials has made it possible to increase the effectiveness of acute infections treatment. However, the infection prevention problem remains unresolved. Here, we demonstrate the fabrication of polylactic acid (PLA) "smart" films with microchamber arrays. These microchambers contain ceftriaxone as a payload in concentrations ranging from 12 ± 1 μg/cm2 to 38 ± 8 μg/cm2, depending on the patterned film thickness formed by the different PLA concentrations in chloroform. In addition, the release profile of the antibiotic can be prolonged up to 72 h in saline. At the same time, on the surface of agar plates, the antibiotic release time increases up to 96 h, which has been confirmed by the growth suppression of the Staphylococcus aureus bacteria. The efficient loading and optimal release rate are obtained for patterned films formed by the 1.5 wt % PLA in chloroform. The films produced from 1.5 and 2 wt % PLA solutions (thickness-0.42 ± 0.12 and 0.68 ± 0.16 µm, respectively) show an accelerated ceftriaxone release upon the trigger of the therapeutic ultrasound, which impacted as an expansion of the bacterial growth inhibition zone around the samples. Combining prolonged drug elution with the on-demand release ability of large cargo amount opens up new approaches for personalized and custom-tunable antibacterial therapy.

SUBMITTER: Mordovina EA

PROVIDER: S-EPMC8781070 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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"Smart" Polylactic Acid Films with Ceftriaxone Loaded Microchamber Arrays for Personalized Antibiotic Therapy.

Mordovina Ekaterina A EA Plastun Valentina O VO Abdurashitov Arkady S AS Proshin Pavel I PI Raikova Svetlana V SV Bratashov Daniil N DN Inozemtseva Olga A OA Goryacheva Irina Yu IY Sukhorukov Gleb B GB Sindeeva Olga A OA

Pharmaceutics 20211226 1

Bacterial infections are a severe medical problem, especially in traumatology, orthopedics, and surgery. The local use of antibiotics-elution materials has made it possible to increase the effectiveness of acute infections treatment. However, the infection prevention problem remains unresolved. Here, we demonstrate the fabrication of polylactic acid (PLA) "smart" films with microchamber arrays. These microchambers contain ceftriaxone as a payload in concentrations ranging from 12 ± 1 μg/cm<sup>2 ...[more]

PMID: 35056938

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Project description:The regeneration of bone remains one of the main challenges in the biomedical field, with the need to provide more personalized and multifunctional solutions. The other persistent challenge is related to the local prevention of infections after implantation surgery. To fulfill the first one and provide customized scaffolds with complex geometries, 3D printing is being investigated, with polylactic acid (PLA) as the biomaterial mostly used, given its thermoplastic properties. The 3D printing of PLA in combination with hydroxyapatite (HA) is also under research, to mimic the native mechanical and biological properties, providing more functional scaffolds. Finally, to fulfill the second one, antibacterial drugs locally incorporated into biodegradable scaffolds are also under investigation. This work aims to develop vancomycin-loaded 3D-printed PLA-HA scaffolds offering a dual functionality: local prevention of infections and personalized biodegradable scaffolds with osseointegrative properties. For this, the antibacterial drug vancomycin was incorporated into 3D-printed PLA-HA scaffolds using three loading methodologies: (1) dip coating, (2) drop coating, and (3) direct incorporation in the 3D printing with PLA and HA. A systematic characterization was performed, including release kinetics, Staphylococcus aureus antibacterial/antibiofilm activities and cytocompatibility. The results demonstrated the feasibility of the vancomycin-loaded 3D-printed PLA-HA scaffolds as drug-releasing vehicles with significant antibacterial effects for the three methodologies. In relation to the drug release kinetics, the (1) dip- and (2) drop-coating methodologies achieved burst release (first 60 min) of around 80-90% of the loaded vancomycin, followed by a slower release of the remaining drug for up to 48 h, while the (3) 3D printing presented an extended release beyond 7 days as the polymer degraded. The cytocompatibility of the vancomycin-loaded scaffolds was also confirmed.

Project description:Microbial pathogenesis is considered one of the most critical health challenges worldwide. Although several antibiotics have been procured and used, the microbes often manage to escape and become resistant to antibiotics. Thus, the discovery of new antibiotics and designing smart approaches toward their delivery are of great importance. In many cases, the delivery agents using foreign chemicals like lipids or polymers induce immunogenic responses of varying degrees and are limited to a shorter circulatory time and burst release. In the current work, we have designed a novel antibiotic delivery system where the antibiotic is encapsulated into a blood component-platelet. Platelets have been previously reported as efficient drug delivery vehicles for targeting cancer cells. On the other hand, during platelet-bacterial interaction, platelets can act as covercytes. Keeping this in mind, smart antibiotic-loaded platelets have been used for killing bacterial cells. The loading of the antibiotic was done using its typical nature of engulfing surrounding small molecules. The water-soluble antibiotics were loaded directly into the platelet, whereas the hydrophobic antibiotics were preloaded in polycaprolactone (FDA-approved polymer)-based nanovesicles to make them solubilized prior to loading inside the platelets. The antibiotic-loaded platelets (containing hydrophilic antibiotics or hydrophobic antibiotic -encapsulated polymer nanoparticles) were found to be stable when studied through platelet aggregometry. The carrier showed bactericidal effects at a significantly lower concentration at which the free antibiotic has negligible efficacy. This could be attributed to the molecular confinement of the antibiotics inside the platelets, therefore causing localization of the drug and leading to efficient activity against bacteria. Interestingly, the smart antibiotic-loaded platelets were capable of killing the resistant strains too at the same lower concentration regime. Therefore, the antibiotic-loaded platelet could emerge as a potential strategy for efficient delivery of antibiotics with a significant reduction of the dose required to achieve the intended antibacterial efficacy. Moreover, this antibiotic delivery method can be very useful to minimize immunogenic responses due to antibiotic administration and to avoid the development of drug resistance due to the invisible mode of delivery.

Dataset Information

"Smart" Polylactic Acid Films with Ceftriaxone Loaded Microchamber Arrays for Personalized Antibiotic Therapy.

Publications

"Smart" Polylactic Acid Films with Ceftriaxone Loaded Microchamber Arrays for Personalized Antibiotic Therapy.

Similar Datasets

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