Template-Free Manufacturing of Defined Structure and Size Polymeric Microparticles

Complex-structured polymeric microparticles hold significant promise as an advance in next-generation medicine mostly due to demand from developing targeted drug delivery. However, the conventional methods for producing these microparticles of defined size, shape, and sophisticated composition often face challenges in scalability, reliance on specialized components such as micro-patterned templates, or limited control over particle size distribution and cargo (functional payload) release kinetics. In this study, we introduce a novel and reliably scalable approach for manufacturing microparticles of defined structures and sizes with variable parameters. The concept behind this method involves the deposition of a specific number of polymer layers on a substrate with low surface energy. Each layer can serve as either the carrier for cargo or a programmable shell-former with predefined permeability. Subsequently, this layered structure is precisely cut into desired-size blanks (particle precursors) using a laser. The manufacturing process is completed by applying heat to the substrate, which results in sealing the edges of the blanks. The combination of the high surface tension of the molten polymer and the low surface energy of the substrate enables the formation of discrete particles, each possessing semi-spherical or other designed geometries determined by their internal composition. Such anisotropic microparticles are envisaged to have versatile applications

Additive Manufacturing of Drug-Eluting Multilayer Biodegradable Films

Drug-eluting films made of bioresorbable polymers are a widely used tool of modern personalized medicine. However, most currently existing methods of producing coatings do not go beyond the laboratory, as they have low encapsulation efficiency and/or difficulties in scaling up. The PLACE (Printed Layered Adjustable Cargo Encapsulation) technology proposed in this article uses an additive approach for film manufacturing. PLACE technology is accessible, scalable, and reproducible in any laboratory. As a demonstration of the technology capabilities, we fabricated layered drug-eluting polyglycolic acid films containing different concentrations of Cefazolin antibiotic. The influence of the amount of loaded drug component on the film production process and the release kinetics was studied. The specific loading of drugs was significantly increased to 200–400 µg/cm2 while maintaining the uniform release of Cefazolin antibiotic in a dosage sufficient for local antimicrobial therapy for 14 days. The fact that the further increase in the drug amount results in the crystallization of a substance, which can lead to specific defects in the cover film formation and accelerated one-week cargo release, was also shown, and options for further technology development were proposed

Synthesis and microbiological properties of novel bis-quaternary ammonium compounds based on biphenyl spacer

Novel gemini (tail-head-spacer-head-tail) bis-quaternary ammonium compounds (bis-QACs) with a biphenyl spacer between two pyridinium heads were synthesized and compared with commonly used antiseptics such as benzalkonium chloride (BAC) and chlorhexidine digluconate (CHG). The series of compounds showed high inhibitory activity against five bacterial strains and two fungi. The compounds, which contain CH-CH aliphatic tails best within the series. A counterion change does not affect MIC in general. Cytotoxicity on human embryonic kidney cells and haemolysis were also investigated. For bis-QACs cytotoxic effect was lower than for 3,3′-[1,4-phenylenebis(oxy)]bis(1-dodecylpyridinium) dibromide (3PHBO-12), that is their closest structural analogue, and for BAC

“Smart” Polylactic Acid Films with Ceftriaxone Loaded Microchamber Arrays for Personalized Antibiotic Therapy

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

Ultrasound-Triggerable Coatings for Foley Catheter Balloons for Local Release of Anti-Inflammatory Drugs during Bladder Neck Dilation

Bladder neck contracture (BNC) is a complication of the surgical treatment of benign and malignant prostate conditions and is associated with the partial or complete blockage of urination. Correction of this condition usually requires repeated surgical intervention, which does not guarantee recovery. Balloon dilation is a minimally invasive alternative to the surgical dissection of tissues; however, it significantly reduces the patient’s quality of life. Additional local anti-inflammatory treatment may reduce the number of procedures requested and increase the attractiveness of this therapeutic strategy. Here, we report about an ultrathin biocompatible coating based on polylactic acid for Foley catheter balloons that can provide localized release of Prednol-L in the range of 56–99 µg in the BNC zone under conventional diagnostic ultrasound exposure. Note that the exposure of a transrectal probe with a conventional gray-scale ultrasound regimen with and without shear wave elastography (SWE) was comparably effective for Prednol-L release from the coating surface of a Foley catheter balloon. This strategy does not require additional manipulations by clinicians. The trigger for the drug release is the ultrasound exposure, which is applied for visualization of the balloon’s location during the dilation process. In vivo experiments demonstrated the absence of negative effects of the usage of a coated Foley catheter for balloon dilation of the bladder neck and urethra