Covalent-driven Layer-by-layer Self-assembly of Clindamycin-loaded PPLA Nanoparticles/chitosan Membrane on Titanium Sheet for Longacting Anti-infection

Abstract

Background: Post-arthroplasty implant-related infection is one of the most feared complications with adverse consequences for patients and public health systems, especially in terms of the huge financial cost of treatment. This is compounded by the potential risks of continuous metamorphosis and emergence of new resistant bacterial strains. Constructing an antibacterial surface therefore on the implant represents an approach to reduce the incidence of implant-related infections. Methods: In this study, a covalent-driven layer-by-layer self-assembly of clindamycin-loaded polyethylene glycol grafted polylactic acid nanoparticles/chitosan membrane has been successfully fabricated on the titanium sheet and evaluated for drug releasing potential and antibiotic activity. Results: Attenuated total reflectance spectrum of the layer-by-layer self-assembly membrane showed three absorption peaks around 1680, 1520 and 1240 cm-1, which are the characteristic absorption peaks of secondary amines. The results indicated the formation of an amide bond between the carboxyl groups of clindamycin-loaded polyethylene glycol grafted polylactic acid nanoparticles and the amino groups of chitosan. The covalent bond stabilized the membrane construct. The membrane exhibited a sustained drug release behavior whereby less than 50% of clindamycin was released after 160 hr. The membrane persistently inhibited the growth of staphylococcus aureus with the inhibition ratio exceeding 60%. Conclusion: The membrane construct holds a great potential for managing anti-implant-related infections.

Clindamycin-loaded titanium prevents implant-related infection through blocking biofilm formation

“…Based on previous research, 36 a minimum of four bilayers were necessary to mask the metal substrate from its environment. And according to our previous research, 25 six bilayers could form a stable structure, and drugs loaded was enough. Therefore, six bilayers were decided.…”

“…The loading of clindamycin was processed according previous study. 25 First, the titanium plate (1cm × 1cm × 1mm) is aminated. In brief, the titanium plate was first polished, and then soaked in 10 M sodium hydroxide (EDC) solution for 6 h. After that, deionized water was used to wash it.…”

“…A method that was modified from previous research 25 was used to measure the dissolution rate of clindamycin here. Briefly, the previously prepared titanium plates were immersed in 1 mL of PBS (pH = 7.4), and placed in the dialysis bag.…”

“…According to the research of Huang Xiao, carboxyl groups of CH-PEG-PLA could connect with chitosan in a covalent bond. 25 At 8 time points we chose, we all detected the presence of clindamycin through high performance liquid chromatography. It proved that clindamycin had been successfully loaded on titanium.…”

Enhancement of mechanical properties of chitosan film by doping with sage extract-loaded niosomes

“…Chitosan films have good mechanical strength, allowing them to be used in many medical applications [14][15][16][17][18], such as tissue engineering and wound care. However, the elasticity, stress resistance, and flexibility of the chitosan films require further improvements [19][20][21].…”