Claire Martin

A review of bacterial cellulose-based drug delivery systems: their biochemistry, current approaches and future prospects.

The field of pharmaceutical technology is expanding rapidly because of the increasing number of drug delivery options. Successful drug delivery is influenced by multiple factors, one of which is the appropriate identification of materials for research and engineering of new drug delivery systems. Bacterial cellulose (BC) is one such biopolymer that fulfils the criteria for consideration as a drug delivery material.

Antimicrobial efficacy of silver ions in combination with tea tree oil against Pseudomonas aeruginosa, Staphylococcus aureus and Candida albicans

Tea tree oil (TTO) and silver ions (Ag(+)), either alone or in combination with other antimicrobial compounds, have been used in the treatment of topical infections. However, there appears to be little data on the efficacy of TTO combined with silver in the absence of any other agents. TTO and Ag(+) were added, alone and in combination, to suspension cultures of Pseudomonas aeruginosa, Staphylococcus aureus and Candida albicans. Treatment of these cultures with TTO and Ag(+) at sub-minimal lethal concentrations resulted in an enhanced loss of viability compared with treatment with individual agents. The order of sensitivity to the combined agents was P. aeruginosa>S. aureus>C. albicans. The fractional lethal concentration index (FLCI) showed that these combinations of TTO and Ag(+) exerted a synergistic effect against P. aeruginosa (FLCI=0.263) and an indifferent effect against S. aureus and C. albicans (FLCI=0.663 and 1.197, respectively). The results indicate that combining these antimicrobial agents may be useful in decreasing the concentration of antimicrobial agents required to achieve an effective reduction in opportunistic pathogenic microorganisms that typically infect wounds.

Strategies for Antimicrobial Drug Delivery to Biofilm

Biofilms are formed by the attachment of single or mixed microbial communities to a variety of biological and/or synthetic surfaces. Biofilm micro-organisms benefit from many advantages of the polymicrobial environment including increased resistance against antimicrobials and protection against the host organisms defence mechanisms. These benefits stem from a number of structural and physiological differences between planktonic and biofilm-resident microbes, but two main factors are the presence of extracellular polymeric substances (EPS) and quorum sensing communication. Once formed, biofilms begin to synthesise EPS, a complex viscous matrix composed of a variety of macromolecules including proteins, lipids and polysaccharides. In terms of drug delivery strategies, it is the EPS that presents the greatest barrier to diffusion for drug delivery systems and free antimicrobial agents alike. In addition to EPS synthesis, biofilm-based micro-organisms can also produce small, diffusible signalling molecules involved in cell density-dependent intercellular communication, or quorum sensing. Not only does quorum sensing allow microbes to detect critical cell density numbers, but it also permits co-ordinated behaviour within the biofilm, such as iron chelation and defensive antibiotic activities. Against this backdrop of microbial defence and cell density-specific communication, a variety of drug delivery systems have been developed to deliver antimicrobial agents and antibiotics to extracellular and/or intracellular targets, or more recently, to interfere with the specific mechanisms of quorum sensing. Successful delivery strategies have employed lipidic and polymeric-based formulations such as liposomes and cyclodextrins respectively, in addition to inorganic carriers e.g. metal nanoparticles. This review will examine a range of drug delivery systems and their application to biofilm delivery, as well as pharmaceutical formulations with innate antimicrobial properties such as silver nanoparticles and microemulsions.

Antimicrobial efficacy of liposome-encapsulated silver ions and tea tree oil against Pseudomonas aeruginosa, Staphylococcus aureus and Candida albicans

The activity of alternative antimicrobial agents such as tea tree oil (TTO) and silver ions (Ag+) with multiple target sites impedes the development of antibacterial resistance and might be useful in improving the current treatment strategies for various chronic wound infections. In this study, liposome‐encapsulated TTO, Ag+ and TTO plus Ag+ were added to suspension cultures of Pseudomonas aeruginosa (Ps. aeruginosa), Staphylococcus aureus (Staph. aureus) and Candida albicans (C. albicans). Treatment of these cultures using the agents in combination at subminimal lethal concentrations resulted in an enhanced loss of viability compared to treatment with individual agents. The effective concentration, elimination time (to the limit of detection, LOD) and fractional lethal concentration index (FLCI) of liposomal agents in combination were as follows: Candida albicans: 0·05% v/v TTO:PVA30‐70 kDa: 8·9 × 10−5% w/v Ag+:PVA30–70 kDa: 2·0 h, FLCI = 0·73 (indifferent), Staphylococcus aureus: 0·05% v/v TTO:PVA30–70 kDa: 6·0 × 10−4% w/v Ag+:PVA30–70 kDa: 1·5 h, FLCI = 0·38 (synergistic), Pseudomonas aeruginosa: 0·25% v/v TTO:PVA30–70 kDa: 3·2 × 10−4% w/v Ag+:PVA30–70 kDa: 30 min, FLCI = 0·33 (synergistic).

Synthesis of a novel acrylated abietic acid-g-bacterial cellulose hydrogel by gamma irradiation.

Acrylated abietic acid (acrylated AbA) and acrylated abietic acid-grafted bacterial cellulose pH sensitive hydrogel (acrylated AbA-g-BC) were prepared by a one-pot synthesis. The successful dimerization of acrylic acid (AA) and abietic acid (AbA) and grafting of the dimer onto bacterial cellulose (BC) was confirmed by 13C solid state NMR as well as FT-IR. X-ray diffraction analysis showed characteristic peaks for AbA and BC; further, there was no effect of increasing amorphous AA content on the overall crystallinity of the hydrogel. Differential scanning calorimetry revealed a glass transition temperature of 80°C. Gel fraction and swelling studies gave insight into the features of the hydrogel, suggesting that it was suitable for future applications such as drug delivery. Scanning electron microscopy observations showed an interesting interpenetrating network within the walls of hydrogel samples with the lowest levels of AA and gamma radiation doses. Cell viability test revealed that the synthesized hydrogel is safe for future use in biomedical applications.

Current trends in the development of wound dressings, biomaterials and devices

Wound management covers all aspects of patient care from initial injury, treatment of infection, fluid loss, tissue regeneration, wound closure to final scar formation and remodeling. There are many wound-care products available including simple protective layers, hydrogels, metal ion-impregnated dressings and artificial skin substitutes, which facilitate surface closure. This review examines recent developments in wound dressings, biomaterials and devices. Particular attention is focused on the design and manufacture of hydrogel-based dressings, their polymeric constituents and chemical modification. Finally, topical negative pressure and hyperbaric oxygen therapy are considered. Current wound-management strategies can be expensive, time consuming and labor intensive. Progress in the multidisciplinary arena of wound care will address these issues and be of immense benefit to patients, by improving both clinical outcomes and their quality of life.

Mucosal delivery of diphtheria toxoid using polymer-coated-bioadhesive liposomes as vaccine carriers

The aim of this study was to prepare stable liposomes coated or loaded with bioadhesive polymers and test their efficacy following oral, nasal (IN) or intramuscular (IM) delivery of diphtheria toxoid (DT) in raising systemic antibody responses. The stability of these liposomes in three different media mimicking gastrointestinal (GI) fluids of the stomach and small intestine was also examined. Fluorescence microscopy of the rat small intestine showed preferential adsorption/association of polymer-coated liposomes versus free FITC-BSA. Finally, the efficacy liposomes composed of dipalmitoylphosphatidylcholine, dicetyl phosphate and cholesterol (DPPC:DCP:CH, 7:3:2 molar ratio) for delivery of DT to mice was assessed. Immunisation through the IM route with these liposomes produced the highest DT specific serum IgG antibody titres; liposomes loaded with chitosan chloride were the only formulation to elicit a specific measurable IgG response when delivered orally with the present protocol. IN delivery of liposomes loaded with PVA resulted in a significantly better IgG antibody response (p < 0.05) when compared to uncoated liposomes.

Essential oils and metal ions as alternative antimicrobial agents: a focus on tea tree oil and silver

The increasing occurrence of hospital‐acquired infections and the emerging problems posed by antibiotic‐resistant microbial strains have both contributed to the escalating cost of treatment. The presence of infection at the wound site can potentially stall the healing process at the inflammatory stage, leading to the development of a chronic wound. Traditional wound treatment regimes can no longer cope with the complications posed by antibiotic‐resistant strains; hence, there is a need to explore the use of alternative antimicrobial agents. Pre‐antibiotic compounds, including heavy metal ions and essential oils, have been re‐investigated for their potential use as effective antimicrobial agents. Essential oils have potent antimicrobial, antifungal, antiviral, anti‐inflammatory, antioxidant and other beneficial therapeutic properties. Similarly, heavy metal ions have also been used as disinfecting agents because of their broad spectrum activities. Both of these alternative antimicrobials interact with many different intracellular components, thereby resulting in the disruption of vital cell functions and eventually cell death. This review will discuss the application of essential oils and heavy metal ions, particularly tea tree oil and silver ions, as alternative antimicrobial agents for the treatment of chronic, infected wounds.

Microwaved bacterial cellulose-based hydrogel microparticles for the healing of partial thickness burn wounds

Burn wound management is a complex process because the damage may extend as far as the dermis which has an acknowledged slow rate of regeneration. This study investigates the feasibility of using hydrogel microparticles composed of bacterial cellulose and polyacrylamide as a dressing material for coverage of partial-thickness burn wounds. The microparticulate carrier structure and surface morphology were investigated by Fourier transform infrared, X-ray diffraction, elemental analysis, and scanning electron microscopy. The cytotoxicity profile of the microparticles showed cytocompatibility with L929 cells. Dermal irritation test demonstrated that the hydrogel was non-irritant to the skin and had a significant effect on wound contraction compared to the untreated group. Moreover, histological examination of in vivo burn healing samples revealed that the hydrogel treatment enhanced epithelialization and accelerated fibroblast proliferation with wound repair and intact skin achieved by the end of the study. Both the in vitro and in vivo results proved the biocompatibility and efficacy of hydrogel microparticles as a wound dressing material.

Characterization and biocompatibility evaluation of bacterial cellulose-based wound dressing hydrogel: effect of electron beam irradiation doses and concentration of acrylic acid.

The use of bacterial cellulose (BC)-based hydrogel has been gaining attention owing to its biocompatibility and biodegradability. This study was designed to investigate the effect of radiation doses and acrylic acid (AA) composition on in vitro and in vivo biocompatibility of BC/AA as wound dressing materials. Physical properties of the hydrogel, that is, thickness, adhesiveness, rate of water vapor transmission, and swelling were measured. Moreover, the effect of these parameters on skin irritation and sensitization, blood compatibility, and cytotoxicity was studied. Increased AA content and irradiation doses increased the thickness, crosslinking density, and improved the mechanical properties of the hydrogel, but reduced its adhesiveness. The swelling capacity of the hydrogel increased significantly with a decrease in the AA composition in simulated wound fluid. The water vapor permeability of polymeric hydrogels was in the range of 2035-2666 [g/(m-2  day-1 )]. Dermal irritation and sensitization test demonstrated that the hydrogel was nonirritant and nonallergic. The BC/AA hydrogel was found to be nontoxic to primary human dermal fibroblast skin cells with viability >88% and was found to be biocompatible with blood with a low hemolytic index (0.80-1.30%). Collectively, these results indicate that these hydrogels have the potential to be used as wound dressings.