betadex and Staphylococcal-Infections

The global threat of antimicrobial resistant strains calls for innovative strategies to utilize nano drug delivery systems to enhance the delivery of antibiotics, thus reducing the development of resistance. Supramolecular amphiphiles that can self-assemble into nanostructures are one such nano delivery system, that are showing potential for effective drug delivery. The aim of this study was to synthesize and formulate a novel sugar-based cationic amphiphile (BCD-OLA) derivative from a Beta-cyclodextrin (BCD) head and long C18 carbon chain with a terminal amine; oleylamine (OLA), using inclusion complexation for application in antibiotic delivery. A suspension method was used for preparing the BCD-OLA amphiphile, which was then utilized for the formulation of nanovesicles. The complexation of BCD-OLA was confirmed by FTIR,

Topics: A549 Cells; Amines; Anti-Bacterial Agents; beta-Cyclodextrins; Cell Line; Cell Line, Tumor; Cell Survival; Chemistry, Pharmaceutical; Drug Delivery Systems; HEK293 Cells; HeLa Cells; Humans; Macrophages; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Nanoparticles; Nanostructures; Particle Size; Staphylococcal Infections; Th1 Cells; Vancomycin

Non-spherical structures are beneficial to advance drug delivery effectiveness compared with common spherical ones, due to increased drug loading capability, improved bonding to a vascular wall, enhanced cellular uptake efficacy and prolonged circulation times. In this study, flower-like Zinc oxide-βcyclodextrin (βCD) nanostructures functionalized by 3-mercaptopropionic acid (MPA) as a non-spherical delivery system was successfully synthesized for aqueous delivery of curcumin (CUR) to enhance its targeting, bioavailability, and release profile. Terminal carboxyl functional groups were used for the conjugation of folic acid (FA) with the aim of active targeting to folate overexpressing breast cancer cells. The in vitro experimental study and mathematical modeling of CUR release revealed a sustained release with Fickian diffusion as the major release mechanism. MTT, colony formation and Annexin-V FITC/PI assays showed the superior anticancer effect of the system compared to free CUR against breast cancer cell line MDA-MB-231 by promoting the apoptotic respond with no cytotoxic effect on HEK293 normal cells. The efficacy of targeting strategy with FA moieties was demonstrated using the augmented cellular uptake of the FA-conjugated system on overexpressed folate receptor alpha (FRα) cells (MDA-MB-468 breast cancer cell line). Furthermore, loading of CUR to the delivery systems significantly lowered the MIC values (2.5 to 5-fold) against S. aureus and E. coli the infections of which are serious problems in cancer patients. According to the results of this study, the system can serve as a promising non-spherical delivery vehicle for enhancing bioavailability and targeting of hydrophobic anticancer agents in the future.

Topics: 3-Mercaptopropionic Acid; Antineoplastic Agents; Apoptosis; beta-Cyclodextrins; Breast Neoplasms; Cell Line, Tumor; Curcumin; Drug Carriers; Escherichia coli; Escherichia coli Infections; Female; Folic Acid; HEK293 Cells; Humans; Nanostructures; Staphylococcal Infections; Staphylococcus aureus; Zinc Oxide

A novel ciprofloxacin loaded chitosan nanoparticle-based coating onto titanium substrates has been developed and characterized to obtain an orthopaedic implant surface able to in situ release the antibiotic for the prevention of post-operative infections. Ciprofloxacin loaded chitosan nanoparticles were obtained using the combination of sulfobutyl ether-beta-cyclodextrin and gamma-cyclodextrin. The resulting nanoparticulate system was characterized by TEM, HPLC and XPS. Particle size was in the range 426-552 nm and zeta potential values were around +30 mV. This antibacterial coating was able to in vitro inhibit two nosocomial Staphylococcus aureus strains growth, with a reduction of about 20 times compared to controls. No impairment in MG63 osteoblast-like cells viability, adhesion and gene expression were detected at 48 h, 7 and 14 days of culture. Overall, the investigated coating represents a promising candidate for the development of a new antibiotic carrier for titanium implants.

Topics: Anti-Bacterial Agents; beta-Cyclodextrins; Cell Line; Chitosan; Ciprofloxacin; Coated Materials, Biocompatible; gamma-Cyclodextrins; Humans; Nanoparticles; Prostheses and Implants; Prosthesis-Related Infections; Staphylococcal Infections; Staphylococcus aureus; Titanium

alpha-Toxin mediates extreme corneal damage during Staphylococcus aureus keratitis. Chemical inhibition of this toxin was sought to provide relief from toxin-mediated pathology.. Inhibition of alpha-toxin by phosphate-buffered saline (PBS), 0.1% methyl-beta-cyclodextrin (CD), or CD plus cholesterol (0.1%, CD-cholesterol) was assayed by hemolysis of rabbit erythrocytes. Pathologic changes in rabbit corneas injected with 12 hemolytic units of alpha-toxin suspended in PBS, 1% CD, or 1% CD-cholesterol were compared over time. Rabbit corneas injected with 10(2) colony forming units (CFU) of S. aureus were treated from 7 to 13 hours postinfection (PI) with a total of 15 drops of CD-cholesterol, CD, or PBS. Slit lamp examination (SLE) and measurement of erosions were performed at 13 hours PI and bacteria were quantified at 14 hours PI.. Toxin-mediated lysis of erythrocytes was inhibited up to 16,000-fold in the presence of CD-cholesterol compared with CD or PBS. Eyes injected with alpha-toxin mixed with CD-cholesterol had, at 7 hours postinjection, significantly smaller erosions than eyes injected with alpha-toxin in PBS or alpha-toxin mixed with CD (P = 0.0090 and P = 0.0035, respectively). Eyes infected with S. aureus and treated with CD-cholesterol had significantly lower SLE scores than eyes treated with CD or PBS (P or= 0.0648).. CD-cholesterol is a potent inhibitor of alpha-toxin activity in vitro and an effective means to arrest corneal damage during S. aureus keratitis.

Topics: Animals; Bacterial Toxins; beta-Cyclodextrins; Cholesterol; Cornea; Corneal Ulcer; Disease Models, Animal; Drug Therapy, Combination; Erythrocytes; Exotoxins; Eye Infections, Bacterial; Hemolysin Proteins; Hemolysis; Rabbits; Sodium Chloride; Staphylococcal Infections; Staphylococcal Toxoid; Staphylococcus aureus; Virulence; Virulence Factors