PLGA microsphere-based composite hydrogel for dual delivery of ciprofloxacin and ginsenoside Rh2 to treat Staphylococcus aureus -induced skin infections

Abstract

When antibiotic-resistant pathogenic bacteria pose a high threat to human health, bacterial multidrug efflux pumps become major contributors to the high-level antibiotic resistance in most microorganisms. Since traditional antibiotics are still indispensable currently, we report a dual drug delivery system to maximize the antibacterial efficacy of antibiotics by inhibiting efflux pumps in bacteria before their exposure to antibiotics. In this research, a microsphere/hydrogel composite was constructed from ciprofloxacin (Cip)-loaded poly (lactic-co-glycolic acid) (PLGA) microspheres and ginsenoside Rh2 (G-Rh2) dispersed thermo-sensitive hydrogel to treat skin infections. In vitro drug release studies indicated that while G-Rh2 in hydrogel presented a faster and short-term release manner to rapidly inhibit the NorA efflux pumps, Cip showed a sustained and long-term release behavior to provide a local high concentration gradient for facilitating drug percutaneous penetration. The combination of Cip and G-Rh2 demonstrated a high degree of synergism against both methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA), hence significantly improving their in vitro antibacterial activity and efficiency. Moreover, the antibacterial performance of the microsphere/hydrogel composite with a sequential release profile is superior to that of other formulations in mouse model of MRSA skin infections, indicating its great potential to treat antibiotic-resistant skin infections.

Poloxamer 407 and Hyaluronic Acid Thermosensitive Hydrogel-Encapsulated Ginsenoside Rg3 to Promote Skin Wound Healing

“…At present, together with the functional hydrogel, the utility of other active pharmaceutical ingredients (such as cells, antibacterial agents, growth factors, drugs, or proteins) produce extremely effective hydrogel dressings for use in wound healing ( Cheng et al, 2020 ). Notably, a recent study exhibited a microsphere/hydrogel composite constructed from ciprofloxacin (Cip)-loaded poly (lactic-co-glycolic acid) (PLGA) microspheres and ginsenoside Rh2 showed excellent potential applications in topical treatment of skin infection ( Sun et al, 2020 ). Furthermore, to prevail the limitations related to ginsenosides delivery, a therapeutic delivery system based on microemulsion composite hydrogel has been designed to improve the low water solubility of ginsenosides ( Kim et al, 2018 ).…”

Membrane-disruptive peptides/peptidomimetics-based therapeutics: Promising systems to combat bacteria and cancer in the drug-resistant era

“…The pHs of acute wounds and the microenvironment of skin cancer are known to be acidic, while chronic wounds and infected wounds with a high bacterial burden usually exhibit pH values above 7.3 252 . Currently, in order to improve skin permeation and stability of drugs, many transdermal drug delivery systems are currently under investigation, including nano- or micro-particles 253 , 254 , 255 , hydrogels 254 , 256 , 257 , and microneedles 258 , 259 , 260 , 261 .…”

Biofunctionalization of Poly(lactide-co-glycolic acid) Using Potent NorA Efflux Pump Inhibitors Immobilized on Nanometric Alpha-Zirconium Phosphate to Reduce Biofilm Formation

“…Moreover, nanocomposites based on PLGA and metal-based nanostructures have shown antimicrobial activity and improved mechanical properties [ 26 , 27 ]. The preparation of PLGA composites containing EPIs as synthetic molecules and even inorganic particles as ZnO [ 28 ] or some essential oils [ 29 ] should be an innovative strategy to prepare films that reduce or reverse bacterial resistance to antibiotics. This work aimed to the preparation of film nanocomposites based on PLGA loaded with nanometric alpha-zirconium phosphate (ZrP) functionalized with potent in-house S. aureus NorA EPIs, belonging to the 2-phenylquinolines class ( 1 and 2 of Figure 1 ) [ 30 ].…”