Polyionic Complexed Antibacterial Heparin–Chitosan Particles for Antibiotic Delivery

Abstract

Efficient delivery of antibacterial agents directly to sites of tissue injury faces challenges such as poor drug stability and fast degradation by biological mechanisms. Biocompatible nanocarrier systems can help sustain and control the delivery of antibacterial compounds while reducing the chances of antibacterial resistance or accumulation in unwanted tissues. In this study, we report the application of tailored polyionic particles via ionic interactions between negatively charged heparin and positively charge chitosan for efficient encapsulation of polyhexamethylene biguanide (PHMB) antibiotic. Negative zeta potential was required to encapsulate the positively charged PHMB. We demonstrate that the ratio of heparin to chitosan can be employed to create a tuned surface charge and maximize the bonding of the drug of choice as well as appropriate particle distribution and uniform morphology. Different formulations were evaluated in terms of size, polydispersity, surface charge, and morphology. Out of all these formulations, the best, negatively charged formulation at four-parts heparin to one-part chitosan was successfully encapsulated with PHMB and showed a sustained and controlled release in vitro for around 10 days. Reduced toxic responses (around 48% reduction) were observed from PHMB-loaded particles in contact with human dermal fibroblasts as compared to the soluble form of PHMB. Finally, in terms of antibacterial properties, the particles resulted in growth inhibition as well as the direct killing of both Gram-positive (Enterococcus faecalis) and Gram-negative (Escherichia coli) bacterial strains. The minimum inhibitory concentrations required to inhibit bacterial growth were determined by microplate dilution and LIVE/DEAD bacterial evaluation.

Feasibility Assessment of Parathyroid Hormone Adsorption by Using Polysaccharide-Based Multilayer Film Systems

“…Generally, the contact angles increased with chitosan as the terminal layer and decreased with heparin as the terminal layer, which is consistent with previous literature [ 18 ]. The contact angle slightly decreased as layer increased, which demonstrated that all of the surfaces are hydrophilic and reflect the antifouling characteristics of the multilayer films [ 18 , 19 ].…”

“…The adsorption of PTH in the presence of BSA on polysaccharide-based multilayer films in PBS was investigated because BSA was identified as one of the most important types of adsorbed proteins in blood–material interaction. Jin et al revealed that polydopamine coated polyurethane film with heparin and carboxymethyl chitosan modification showed a significant decrease of protein adsorption and enhancement of hemocompatibility and antibacterial properties in comparison with polyurethane film [ 19 , 21 ]. Heparin/chitosan complex materials and modification have been widely evidenced to increase hydrophilicity, decrease BSA and fibrinogen adsorption and enhance blood compatibility [ 22 ].…”

“…The adsorbed masses of PTH on the (chitosan/heparin) 2.5 multilayer film was higher than that of other multilayer films, and this might be attributed to the hydrophilicity, positive charge of the surface and optimized rougher surfaces of the (chitosan/heparin) 2.5 multilayer film. For this reason, the (chitosan/heparin) 2.5 multilayer film was expected to have improved anti-fouling activities, such as reduced nonspecific protein adsorption and decreased bacterial adhesion [ 18 , 19 ].…”

“…It has been shown to prevent bacterial infection in the early stages of surgery and promote wound healing [ 14 , 15 , 16 ]. The combination of these two polyelectrolytes, heparin and chitosan, has shown enormous potential in a variety of applications including drug delivery, dental repair and vascular treatment [ 16 , 17 , 18 , 19 ].…”

Fluorinated Chitosan Microgels to Overcome Internal Oxygen Transport Deficiencies in Microtissue Culture Systems

“…[ 17 ] Chitosan is primarily sourced as a shellfish byproduct, as was used in this study, however, newer high purity fermentation sourced chitosan has now become available to reduce sourcing concerns. [ 18 ] The ability to perform amine targeted bioconjugations to the chitosan polymer backbone allows straightforward covalently tethering of PFCs [ 12 ] to provide stability and confirming the ability to manipulate and utilize PFCs in new applications.…”