Vancomycin-loaded HPMC microparticles embedded within injectable thermosensitive chitosan hydrogels

Abstract

Antibiotic use is an essential method for the treatment of bacterial infections. In certain cases, antibiotics are not effective because of the distribution problems caused by physiological barriers in the body. Such problems are thought to be minimized by development of sustained release systems which involve implantation of antibiotic loaded polymeric systems directly to the site of infection. In this work, a new composite vancomycin hydrochloride release system based on HPMC microparticles and chitosan/glycerophosphate (Ch/Gp) thermosensitive hydrogel was designed for the aim of local treatment of osteomyelitis. Vancomycin-loaded HPMC microparticles (Van-HPMCs) were prepared by spray drying method. The SEM results showed that these particles had a mean diameter of 1.5–6.4 μm with a narrow size distribution and homogeneous particle production. Their drug encapsulation efficiency was 72.6%. The Van-HPMCs were embedded in an injectable Ch/Gp solution to introduce a composite drug release platform (Van/HPMC-Ch/Gp). In vitro release studies indicated that inclusion of the Van-HPMCs into the Ch/Gp hydrogel caused a reduction in both the release rate and total amount of vancomycin release, which suggests that HPMC microparticles entrapped into the Ch/Gp hydrogels showed more suitable sustained release kinetics for local antibiotics delivery.

Therapeutics and delivery vehicles for local treatment of osteomyelitis

“…101,109 Hydrogels are generally biodegradable and may be cleared by the body in as early as 2 to 6 weeks. 101,105,109 Hydrogels have been used as carriers for antibiotics, 103,105,108,110,111 bacteriophages, 34,42,47,106 and proteins, 42,49,71,74 as well as nanoparticles and microparticles containing therapeutics. 94,105,110 One of the advantages of hydrogels is the ability to tailor their properties including porosity, viscosity, elasticity, degree of swelling, and rate of drug elution.…”

“…To alter drug elution rates, the sensitivity of hydrogels to temperature, pH, or both can be altered to increase or decrease degradation rates. 21,104,105,108,110 Another way to modify drug elution rate is through changes in the composition of the gels.…”

“…122 poly(N-isopropylacrylamide) (PNIPAM), 129 gold, 47,94,130 silver, 94,131 silk fibroin, 94,127 chitosan, 132 chitosan/silver-hydroxyapatite blends, 133 and PLGA. 105,112,126,128 Chitosan-glycerophosphate, 110 gelatin, 102 and a mixture of chitosan and gelatin cross-linked with genipin have also been used. 134 As an alternative to the more expensive gold micro-and na- Micro-and nanoparticles may be used for local or systemic delivery of therapeutics.…”

“…Hydrogels are a common way these particles have been delivered to the site of infection. 110,112 Oral ingestion has been considered, although stomach acid can hinder the effectiveness of phages and antibiotics. Thus, extra measures must be taken to protect microspheres, which can involve encapsulation by a basic COBB ET AL.…”

Cellulose-based hydrogel materials: chemistry, properties and their prospective applications

“…Cellulose-based composite hydrogels are made by blending natural biodegradable polymers or synthetic polymers with cellulose or its derivatives such as chitin, chitosan (Long and Luyen 1996 ; Mahmoudian and Ganji 2017 ) and starch (Faroongsarng and Sukonrat 2008 ) to achieve a new structural design and functional properties (Bajpai et al 2008 ). For instance, phase-separated composite hydrogels have been prepared by blending cellulose and chitin in thiourea aqueous solution in the presence of H 2 SO 4 as coagulant (Zhou et al 2004 ).…”