Bingbing Jiang

Multilayer polypeptide nanoscale coatings incorporating IL-12 for the prevention of biomedical device-associated infections

Biomedical device-associated infection is one of the most common and problematic complications faced by millions of patients worldwide. The current antibiotic therapy strategies face challenges, the most serious of which is antibiotic resistance. Studies have shown that the systemic level of interleukin 12 (IL-12) decreases following major injuries resulting in decreased cell-mediated immune response. Here we report the development of IL-12 nanoscale coatings using electrostatic layer-by-layer self-assembly nanotechnology. We found that IL-12 nanoscale coatings at the implant/tissue interface substantially decrease infections in vivo, and IL-12 nanoscale coatings are advantageous over traditional treatments. This approach could be a revolutionary step toward preventing device-associated infections using a non-antibiotic approach.

Evaluation of local MCP-1 and IL-12 nanocoatings for infection prevention in open fractures

The increasing incidence of bacterial infection and the appearance of Staphylococcus aureus (S. aureus) strains that are resistant to commonly used antibiotics has made it important to develop non‐antibiotic approaches for infection prevention. The aim of this study was to develop local monocyte chemoattractant protein‐1 (MCP‐1) and interleukin‐12 p70 (IL‐12 p70) therapies to prevent S. aureus infection by enhancing the recruitment and activation of macrophages, which are believed to play an important role in infection prevention as the first line of defense against invading pathogens. Nanocoating systems for MCP‐1 and IL‐12 p70 deliveries were prepared, and their release characteristics desirable for infection prevention in open fractures were explored. Local MCP‐1 therapy reduced S. aureus infection and influenced white blood cell populations, and local IL‐12 p70 treatment had a more profound effect on preventing S. aureus infection. No synergistic relationship in decreasing S. aureus infection was observed when MCP‐1 and IL‐12 p70 treatments were combined. This reported new approach may reduce antibiotic use and antibiotic resistance.

Tunable drug loading and release from polypeptide multilayer nanofilms

Polypeptide multilayer nanofilms were prepared using electrostatic layer-by-layer self-assembly nanotechnology. Small charged drug molecules (eg, cefazolin, gentamicin, and methylene blue) were loaded in polypeptide multilayer nanofilms. Their loading and release were found to be pH-dependent and could also be controlled by changing the number of film layers and drug incubation time, and applying heat-treatment after film formation. Antibioticloaded polypeptide multilayer nanofilms showed controllable antibacterial properties against Staphylococcus aureus. The developed biodegradable polypeptide multilayer nanofilms are capable of loading both positively- and negatively-charged drug molecules and promise to serve as drug delivery systems on biomedical devices for preventing biomedical device-associated infection, which is a significant clinical complication for both civilian and military patients.

Kaempferol nanoparticles achieve strong and selective inhibition of ovarian cancer cell viability

Ovarian cancer is one of the leading causes of cancer death for women throughout the Western world. Kaempferol, a natural flavonoid, has shown promise in the chemoprevention of ovarian cancer. A common concern about using dietary supplements for chemoprevention is their bioavailability. Nanoparticles have shown promise in increasing the bioavailability of some chemicals. Here we developed five different types of nanoparticles incorporating kaempferol and tested their efficacy in the inhibition of viability of cancerous and normal ovarian cells. We found that positively charged nanoparticle formulations did not lead to a significant reduction in cancer cell viability, whereas nonionic polymeric nanoparticles resulted in enhanced reduction of cancer cell viability. Among the nonionic polymeric nanoparticles, poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) nanoparticles incorporating kaempferol led to significant reduction in cell viability of both cancerous and normal cells. Poly(DL-lactic acid-co-glycolic acid) (PLGA) nanoparticles incorporating kaempferol resulted in enhanced reduction of cancer cell viability together with no significant reduction in cell viability of normal cells compared with kaempferol alone. Therefore, both PEO-PPO-PEO and PLGA nanoparticle formulations were effective in reducing cancer cell viability, while PLGA nanoparticles incorporating kaempferol had selective toxicity against cancer cells and normal cells. A PLGA nanoparticle formulation could be advantageous in the prevention and treatment of ovarian cancers. On the other hand, PEO-PPO-PEO nanoparticles incorporating kaempferol were more effective inhibitors of cancer cells, but they also significantly reduced the viability of normal cells. PEO-PPO-PEO nanoparticles incorporating kaempferol may be suitable as a cancer-targeting strategy, which could limit the effects of the nanoparticles on normal cells while retaining their potency against cancer cells. We have identified two nanoparticle formulations incorporating kaempferol that may lead to breakthroughs in cancer treatment. Both PEO-PPO-PEO and PLGA nanoparticle formulations had superior effects compared with kaempferol alone in reducing cancer cell viability.

Cefazolin Embedded Biodegradable Polypeptide Nanofilms Promising for Infection Prevention: A Preliminary Study on Cell Responses

Implant‐associated infection is a serious complication in orthopedic surgery, and endowing implant surfaces with antibacterial properties could be one of the most promising approaches for preventing such infection. In this study, we developed cefazolin loaded biodegradable polypeptide multilayer nanofilms on orthopedic implants. We found that the amount of cefazolin released could be tuned. A high local concentration of cefazolin was achieved within the first a few hours and therefore may inhibit bacterial colonization in the critical postimplantation period. The developed cefazolin loaded nanofilms showed their in vitro efficacy against Staphylococcus aureus; the more antibiotics loaded, the longer the nanocoated implant had antibacterial properties. More interestingly, antibiotic‐loaded polypeptide multilayer nanofilms also improved osteoblast bioactivity including cell viability and proliferation. These findings suggested that biodegradable polypeptide multilayer nanofilms as antibiotic carriers at the implant/tissue interface are compatible with human cells such as osteoblasts and bactericidal to bacteria such as S. aureus. These characteristics could be promising for preventing implant‐associated infection and potentially improving bone healing.

Advances in polyelectrolyte multilayer nanofilms as tunable drug delivery systems

There has been considerable interest in polyelectrolyte multilayer nanofilms, which have a variety of applications ranging from optical and electrochemical materials to biomedical devices. Polyelectrolyte multilayer nanofilms are constructed from aqueous solutions using electrostatic layer-by-layer self-assembly of oppositely-charged polyelectrolytes on a solid substrate. Multifunctional polyelectrolyte multilayer nanofilms have been studied using charged dyes, metal and inorganic nanoparticles, DNA, proteins, and viruses. In the past few years, there has been increasing attention to developing polyelectrolyte multilayer nanofilms as drug delivery vehicles. In this mini-review, we present recent developments in polyelectrolyte multilayer nanofilms with tunable drug delivery properties, with particular emphasis on the strategies in tuning the loading and release of drugs in polyelectrolyte multilayer nanofilms as well as their applications.

Biomimetic nanocoating promotes osteoblast cell adhesion on biomedical implants

Implantation of dental and orthopaedic devices is affected by delayed or weak implant-bone integration and inadequate new bone formation. Innovative approaches have been sought to enhance implant-bone interaction to achieve rapid osseointegration. The aim of this study was to develop biomimetic polypeptide nanocoatings and to evaluate cell adhesion, proliferation, morphology, and biocompatibility of polypeptide nanocoatings on implant surfaces. A recently developed nanotechnology, i.e., electrostatic self-assembly, was applied to build polypeptide nanocoatings on implant models, i.e., stainless steel discs. Our in vitro tests using human osteoblast cells revealed that substantially more (one order magnitude higher) osteoblast cells were attached to polypeptide-coated, stainless steel discs than to uncoated discs within the first few hours of contact. The developed biomimetic nanocoatings may have great potential for dental and orthopaedic applications.

Polypeptide multilayer film co-delivers oppositely-charged drug molecules in sustained manners.

The current state-of-the-art for drug-carrying biomedical devices is mostly limited to those that release a single drug. Yet there are many situations in which more than one therapeutic agent is needed. Also, most polyelectrolyte multilayer films intended for drug delivery are loaded with active molecules only during multilayer film preparation. In this paper, we present the integration of capsules as vehicles within polypeptide multilayer films for sustained release of multiple oppositely charged drug molecules using layer-by-layer nanoassembly technology. Calcium carbonate (CaCO(3)) particles were impregnated with polyelectrolytes, shelled with polyelectrolyte multilayers, and then assembled onto polypeptide multilayer films using glutaraldehyde. Capsule-integrated polypeptide multilayer films were obtained after decomposition of CaCO(3) templates. Two oppositely charged drugs were loaded into capsules within polypeptide multilayer films postpreparation based on electrostatic interactions between the drugs and the polyelectrolytes impregnated within capsules. We determined that the developed innovative capsule-integrated polypeptide multilayer films could be used to load multiple drugs of very different properties (e.g., opposite charges) any time postpreparation (e.g., minutes before surgical implantation inside an operating room), and such capsule-integrated films allowed simultaneous delivery of two oppositely charged drug molecules and a sustained (up to two weeks or longer) and sequential release was achieved.

Nanoparticles targeting to osteoblasts for potential intracellular pathogen elimination

A number of techniques have been developed to incorporate watersoluble drugs into electrospun fibers to achieve sustained drug release [1]. However, problems including burst and uncontrolled release still remain to be solved [2]. In this study, we developed a microsol-electrospinning technique for fabricating core–shell nanofibers to achieve incubated, controlled and sustainable releases of water-soluble drugs such as chloroquine (CQ) (Fig. 1). In this approach, nanoparticles made of CQloaded hyaluronic acid (HA) sol were first prepared using ultrasonic emulsification method. Next, the HA-sol nanoparticles were dispersed in poly(l-lactide) (PLLA) electrospinning solution to form a uniform suspension, whichwas used for fabricating composite nanofibers through microsol-electrospinning. The composite nanofibers had smooth, uniform morphology and core–shell structure. Further tests showed that the microsol-electrospun nanofibers had similar physical, chemical, and mechanical properties as nanofibers fabricated using conventional electrospinning approach. In vitro drug release test showed that compared to conventional electrospun nanofibers, the burst release of CQ was significantly reduced in microsol-electrospun nanofibers. Meanwhile, the release time of CQ was markedly extended, being as long as more than 40 days. Importantly, the drug releasing rate could be readily adjusted by changing the concentration of microsol particles and the amount of drug in the nanofibers. Together, findings from this study indicate that microsol-electrospinning is a facile technique for loading water-soluble drugs into electrospun nanofibers and releasing them in a controlled fashion, which may expand the applications of water-soluble drugs.