Intelligent-Responsive Enrofloxacin-Loaded Chitosan Oligosaccharide–Sodium Alginate Composite Core-Shell Nanogels for On-Demand Release in the Intestine

Abstract

Enrofloxacin has a poor palatability and causes strong gastric irritation; the oral formulation of enrofloxacin is unavailable, which limits the treatment of Escherichia coli (E. coli) infections via oral administration. To overcome the difficulty in treating intestinal E. coli infections, an oral intelligent-responsive chitosan-oligosaccharide (COS)–sodium alginate (SA) composite core-shell nanogel loaded with enrofloxacin was explored. The formulation screening, characteristics, pH-responsive performance in gastric juice and the intestinal tract, antibacterial effects, therapeutic effects, and biosafety level of the enrofloxacin composite nanogels were investigated. The optimized concentrations of COS, SA, CaCl2, and enrofloxacin were 8, 8, 0.2, and 5 mg/mL, respectively. The encapsulation efficiency, size, loading capacity, zeta potential, and polydispersity index of the optimized formulation were 72.4 ± 0.8%, 143.5 ± 2.6 nm, 26.6 ± 0.5%, −37.5 ± 1.5 mV, and 0.12 ± 0.07, respectively. Scanning electron microscopy images revealed that enrofloxacin-loaded nanogels were incorporated into the nano-sized cross-linked networks. Fourier transform infrared spectroscopy showed that the nanogels were prepared by the electrostatic interaction of the differently charged groups (positive amino groups (-NH3+) of COS and the negative phenolic hydroxyl groups (-COO−) of SA). In vitro, pH-responsive release performances revealed effective pH-responsive performances, which can help facilitate targeted “on-demand” release at the target site and ensure that the enrofloxacin has an ideal stability in the stomach and a responsive release in the intestinal tract. The antibacterial activity study demonstrated that more effective bactericidal activity against E. coli could have a better treatment effect than the enrofloxacin solution. Furthermore, the enrofloxacin composite nanogels had great biocompatibility. Thus, the enrofloxacin composite core-shell nanogels might be an oral intelligent-responsive preparation to overcome the difficulty in treating intestinal bacterial infections.

Antibiofilm activity of polyethylene glycol-quercetin nanoparticles-loaded gelatin-N,O-carboxymethyl chitosan composite nanogels againstStaphylococcus epidermidis

“…PQ-nanogels were formulated by hot melt homogenization with the ultrasonic method and electrostatic interaction [ 14 ]. Briefly, 1.0 g PEG was added to 10 mL of ultrapure water with magnetic stirring and heat using a magnetic stirrer (GL-3250A; Kylin-Bell Lab Instruments, China) for complete dissolution to obtain the PEG solution.…”

Chitosan/Alginate-Based Nanoparticles for Antibacterial Agents Delivery

“… [ 119 ] Amoxicillin (AMX) combined with docosahexaenoic acid (DHA) Oil-in-water emulsification combined with ionic gelation method In vivo Helicobacter pylori Growth inhibition rate level: AMX-DHA-loaded NPs > AMX-loaded NPs > DHA-loaded NPs > Blank NPs The system is capable of loading multiple components, providing additive properties from the addition of DHA [ 111 ] Enrofloxacin Ionic gelation method In vitro and in vivo Escherichia coli MIC: Free Enrofloxacin = 1 µg/mL Enrofloxacin-loaded NPs = 0.125 µg/mL Drug delivery in the nano-system protects the drug from negative exposure, thereby indirectly increasing efficacy. [ 112 ] Doxycycline Ionotropic Gelation Method In vitro Proteus mirabilis, Escherichia coli , and Enterococcus faecalis Inhibition rate: Doxycycline-loaded NPs > Blank NPs > Free Doxycycline > Negative Control Synergistic effects arise from the nano-charge of alginate guided by non-ionic interactions between chitosan and bacterial peptidoglycan teichoic acid. [ 113 ] Rifampicin (RIF) and ascorbic acid (ASC) Ionic gelation method In vitro Staphylococcus aureus MIC: Free Rifampicin = 0.2 μg/mL RIF-ASC mixture = 0.2 μg/mL Blank NPs = no inhibition RIF-ASC-loaded NPs = <0.025 μg/mL The primary mechanism of nanoparticle delivery is through the destruction of bacterial cell walls, allowing the encapsulated active substances to efficiently reach their targets within bacterial cells.…”

“…From penicillins, aminoglycosides, fluoroquinolones, rifampicin, to polypeptides such as daptomycin, and glycopeptides like vancomycin, all can be harnessed through this approach. [108][109][110][111][112][113][114][115][116][117] These nanoparticles adeptly tackle various physicochemical challenges associated with antibiotics, notably by ameliorating solubility issues. For instance, the solubility of amoxicillin, typically sparingly soluble in water, can be significantly enhanced through this strategy.…”

Current Advances in Stimuli-Responsive Hydrogels as Smart Drug Delivery Carriers

“…Over the past few years, one of the main advancements in this field has been the development of pH-responsive hydrogels and nanogels with improved biocompatibility and drug-loading capacity. Researchers have explored natural polymers like chitosan and alginate, along with biocompatible polymers such as hydroxypropyl methylcellulose (HPMC), to create pH-sensitive hydrogels that are both biodegradable and safe [75][76][77].…”