Lehar et al

Lehar et al. delivery). The review concludes with future perspectives and associated challenges for developing local drug delivery for musculoskeletal applications. (by inhibiting their cell wall synthesis. More strikingly, no mutants of these bacteria were observed. Lehar et al. introduced a novel antibody-antibiotic conjugate to eliminate intracellular [46]. This conjugate consists of an anti-antibody and a highly efficacious antibiotic (Figure 2b) and was found to be superior to conventional antibiotics like vancomycin. This provides a new strategy to design and develop novel antimicrobial drugs against intracellular or MRSA [39]. Liu et al. reported the fabrication of novel poly(lactic-co-glycolic acid)-dextran (PLGAD)-based delivery vehicles and used them to deliver anti-cancer drug of cisplatin (CDDP) for osteosarcoma cells [101]. The results showed that PLGAD/CDDP exhibited robust anti-tumor activity and could provide a promising platform in the treatment of osteosarcoma. In addition, Huang et al. developed a novel bone-targeting liposome which contains an oligopeptide of eight aspartate residues, and showed that this delivery system TNP-470 could effectively carry osteogenic phytomolecules to prevent estrogen depletion-induced osteoporosis [102]. Open in a separate window Figure 3. (a) Schematic illustrations of construction of KGN-PAMAM conjugates. (b) Illustration of the synthetic procedure for the anti-EGFR functionalized and dendrimer-assisted hydrophilic magnetic nanoparticles and the applications in cell capture. (c) Proposed liposome-pluronics structure. (d) The nanofiber-film coating was prepared by coelectrospinning of antibiotic-loaded PLGA and PCL fibers simultaneously onto the titanium K-wire implants followed by heat treatment to generate a conformal PCL film embedded with PLGA fibers. (e) Schematic illustration of the formation of a highly adhesive, multifunctional hydrogel coating on Ti TNP-470 surfaces. (f) Photo-crosslinlkable nanocomposite hydrogels comprised of silicate nanoplatelets, GelMA and hMSC derived growth factors (secretome), and microbioreactor with deep concave wells to harness hMSC secretome. Reprinted from [45,99,100,104,114,116] with permissions from American Chemical Society, Royal Society TNP-470 of Chemistry, Elsevier, Wiley-VCH., and National Acad Sciences. Delivery vehicles in the form of nano/microparticles are one of the main categories of drug carriers for the treatment of musculoskeletal diseases, because of their unique properties stemming Rabbit Polyclonal to ATG4C from their nanostructures [104,116C121]. Besides the common nanoparticles like mesoporous silica particles, polymeric particles, etc., many novel forms including micelles, emulsion particles, magnetic particles, liposomes, and microbubbles have been studied [103,119,120,122]. Li et al. reported an effective method to fabricate lignin-based complex micelles in an ethanol/water mixture; these micelles were pH-responsive and exhibited controlled release properties for ibuprofen delivery in the treatment of a variety of musculoskeletal disorders and painful conditions [103]. Zhang et al. developed docetaxel emulsion particles which TNP-470 were coated with denatured soy protein isolates using an anti-solvent precipitation-ultrasonication technique [104]. The solubility of docetaxel nanoparticles was improved and led to high internalization into cancer cells, thus achieving enhanced cell cytotoxicity against musculoskeletal cancer cells. Talaie et al. used superparamagnetic iron oxide nanoparticles as vehicles to facilitate the monitoring and control of platelet-rich plasma (PRP) with noninvasive tools, thus achieving site-specific targeting of PRP for the treatment of injured muscle tissues [105]. Ayre et al. developed a novel delivery vehicle based on antibiotic-loaded nano-sized liposomes (Figure 3c), which resulted in a controlled and gradual release of antibiotic over a long period [106]. The results showed that the liposomal drug delivery system provided a potential platform TNP-470 to reduce infections in cemented joint replacements. In addition, a combined ultrasound-and-microbubble-mediated diclofenac gel delivery was developed which showed enhanced efficacy for the treatment of adjuvant-induced rheumatoid arthritis in rats [107]. Musculoskeletal implants may provide mechanical stability and may also need to have the capability to deliver drugs at the site of injury to promote healing and/or to prevent infections. Compared to other methods, implant coating has attracted extensive attention because of its integrated features of simplicity and versatility. A polymeric nanofiber coating with tunable combinatorial antibiotic delivery was developed by Ashbaugh et al. using electrospinning [108]. The coelectrospinning strategy is illustrated in Figure 3d. The antibiotic-loaded poly(lactic-co-glycolic acid) (PLGA) nanofibers and PCL were deposited on implants and generated conformal films after heat treatment. The coatings presented controlled release of antimicrobial agents and could prevent biofilm-associated infection experiments. The results showed significantly enhanced cell proliferation and osteoconductivity, indicating the promising capability of this scaffold as a useful construct for bone tissue engineering. Trombetta et al. reviewed the preparation of calcium phosphate.