Development and
            <i>In Vivo</i>
            Evaluation of a Novel Histatin-5 Bioadhesive Hydrogel Formulation against Oral Candidiasis

Kong, Eric F.; Tsui, Christina; Boyce, Heather; Ibrahim, Ahmed; Hoag, Stephen W.; Karlsson, Amy J.; Meiller, Timothy F.; Jabra‐Rizk, Mary Ann

doi:10.1128/aac.02624-15

Cited by 42 publications

(41 citation statements)

References 44 publications

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“…A major focus in the medical development of histatins has been in the preparation of formulations to treat oral diseases and infections [141]. For example, highly effective hydrogel delivery systems for the topical and oral application of hst-5 have been developed for the treatment of oral candidiasis [261], which is the most common opportunistic fungal infection in immunocompromised populations [262]. High potential for the topical treatment of this fungal condition was also demonstrated when derivatives of hst-5 were conjugated to spermidine and tested on immunocompromised murine models [263].…”

Section: Potential Applications Of Ph Dependent Antimicrobial Peptmentioning

confidence: 99%

pH Dependent Antimicrobial Peptides and Proteins, Their Mechanisms of Action and Potential as Therapeutic Agents

et al. 2016

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Antimicrobial peptides (AMPs) are potent antibiotics of the innate immune system that have been extensively investigated as a potential solution to the global problem of infectious diseases caused by pathogenic microbes. A group of AMPs that are increasingly being reported are those that utilise pH dependent antimicrobial mechanisms, and here we review research into this area. This review shows that these antimicrobial molecules are produced by a diverse spectrum of creatures, including vertebrates and invertebrates, and are primarily cationic, although a number of anionic examples are known. Some of these molecules exhibit high pH optima for their antimicrobial activity but in most cases, these AMPs show activity against microbes that present low pH optima, which reflects the acidic pH generally found at their sites of action, particularly the skin. The modes of action used by these molecules are based on a number of major structure/function relationships, which include metal ion binding, changes to net charge and conformational plasticity, and primarily involve the protonation of histidine, aspartic acid and glutamic acid residues at low pH. The pH dependent activity of pore forming antimicrobial proteins involves mechanisms that generally differ fundamentally to those used by pH dependent AMPs, which can be described by the carpet, toroidal pore and barrel-stave pore models of membrane interaction. A number of pH dependent AMPs and antimicrobial proteins have been developed for medical purposes and have successfully completed clinical trials, including kappacins, LL-37, histatins and lactoferrin, along with a number of their derivatives. Major examples of the therapeutic application of these antimicrobial molecules include wound healing as well as the treatment of multiple cancers and infections due to viruses, bacteria and fungi. In general, these applications involve topical administration, such as the use of mouth washes, cream formulations and hydrogel delivery systems. Nonetheless, many pH dependent AMPs and antimicrobial proteins have yet to be fully characterized and these molecules, as a whole, represent an untapped source of novel biologically active agents that could aid fulfillment of the urgent need for alternatives to conventional antibiotics, helping to avert a return to the pre-antibiotic era.

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Section: Potential Applications Of Ph Dependent Antimicrobial Peptmentioning

confidence: 99%

pH Dependent Antimicrobial Peptides and Proteins, Their Mechanisms of Action and Potential as Therapeutic Agents

et al. 2016

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“…While it is clear that innate defenses (salivary flow, antimicrobial peptides) help limit C. albicans overgrowth in the oral cavity, it became quite clear during the HIV epidemic that CD4 ϩ T cells were the primary protective host defense mechanism against OPC (37,38,(41)(42)(43)(44)(45)(46). An established mouse model of OPC has been widely used for investigating Candida virulence factors, immune mechanisms against candidiasis, and the efficacy of antifungal agents (4).…”

Section: Fitting C Albicans Within the Damage Response Frameworkmentioning

confidence: 99%

Candida albicans Pathogenesis: Fitting within the Host-Microbe Damage Response Framework

et al. 2016

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f Historically, the nature and extent of host damage by a microbe were considered highly dependent on virulence attributes of the microbe. However, it has become clear that disease is a complex outcome which can arise because of pathogen-mediated damage, host-mediated damage, or both, with active participation from the host microbiota. This awareness led to the formulation of the damage response framework (DRF), a revolutionary concept that defined microbial virulence as a function of host immunity. The DRF outlines six classifications of host damage outcomes based on the microbe and the strength of the immune response. In this review, we revisit this concept from the perspective of Candida albicans, a microbial pathogen uniquely adapted to its human host. This fungus commonly colonizes various anatomical sites without causing notable damage. However, depending on environmental conditions, a diverse array of diseases may occur, ranging from mucosal to invasive systemic infections resulting in microbe-mediated and/or host-mediated damage. Remarkably, C. albicans infections can fit into all six DRF classifications, depending on the anatomical site and associated host immune response. Here, we highlight some of these diverse and site-specific diseases and how they fit the DRF classifications, and we describe the animal models available to uncover pathogenic mechanisms and related host immune responses.

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“…Curcumin-loaded polymeric nanoparticles were demonstrated to improve the antimicrobial effect of photodynamic therapy for oral candidiasis [194]. Antimicrobial peptides loaded BDDS were also reported and presented a controlled release and antifungal activity in vitro and in vivo [57]. Oral candidiasis that associated with complete or removable partial dentures in the elderly called denture stomatitis is an important part of the research (Figure 6d).…”

Section: Dds For Oral Candidiasismentioning

confidence: 99%

“…Application Oral Diseases Composition micro/nano particles micro/nano sphere dental caries [31,35] periodontitis [38] implant coating [50,51] oral candidiasis [52] PLGA, PDLLA, PEG and biopolymers like lipid, chitosan, pectin, and alginate nanofiber periodontitis [19] oral candidiasis [53] implant coating [43] nano capsule dental resin modification [42] hydrogel dental caries [54] periodontitis [55,56] oral candidiasis [57] Hydrophilic groups such as -OH, -CONH-, -CONH2dendrimer dental caries [58] PAMAM, poly(aryl ether) Figure 1. Examples of the structures of different kinds of carriers.…”

Section: Types Of Carriersmentioning

confidence: 99%

“…In the clinic study, the varnish was applied to the denture once a day and the candida level was significantly reduced after 14 days of treatment [195]. Modified drug delivery denture was also a novel treatment for oral candidiasis [57]. Wen et al showed denture surface grafted with miconazole loaded polymers with sustained drug release and robust biofilm controlling effect [196].…”

Section: Dds For Oral Candidiasismentioning

confidence: 99%

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Emerging Applications of Drug Delivery Systems in Oral Infectious Diseases Prevention and Treatment

et al. 2020

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The oral cavity is a unique complex ecosystem colonized with huge numbers of microorganism species. Oral cavities are closely associated with oral health and sequentially with systemic health. Many factors might cause the shift of composition of oral microbiota, thus leading to the dysbiosis of oral micro-environment and oral infectious diseases. Local therapies and dental hygiene procedures are the main kinds of treatment. Currently, oral drug delivery systems (DDS) have drawn great attention, and are considered as important adjuvant therapy for oral infectious diseases. DDS are devices that could transport and release the therapeutic drugs or bioactive agents to a certain site and a certain rate in vivo. They could significantly increase the therapeutic effect and reduce the side effect compared with traditional medicine. In the review, emerging recent applications of DDS in the treatment for oral infectious diseases have been summarized, including dental caries, periodontitis, peri-implantitis and oral candidiasis. Furthermore, oral stimuli-responsive DDS, also known as "smart" DDS, have been reported recently, which could react to oral environment and provide more accurate drug delivery or release. In this article, oral smart DDS have also been reviewed. The limits have been discussed, and the research potential demonstrates good prospects.Molecules 2020, 25, 516 2 of 29 problems. For example, systemic antibiotics such as tetracycline, beta-lactam antibiotics, nitroimidazoles have been used, especially in cases of periodontal diseases and peri-implantitis [12]. However, systemic antibiotics could cause problems like drug resistance, dysbacteriosis, and systemic side effects [13,14]. The antibacterial effect is also limited as very little could arrive at the oral lesion area after systemic circulation [15][16][17]. Fluoride in drinking water has been used for the prevention of dental caries but might cause excessive intake, leading to fluorosis [18]. Therefore, local drug therapy is now more considered for oral infectious diseases [19,20]. However, the conventional forms of local therapy, like drug suspension or rinse of anti-infection agents, could be easily washed off and thus could not last long in the oral cavity. Complex local lesions like deep periodontal pockets and teeth fissure are also difficult to reach. In order to improve the effect of prophylaxis and treatment, more precise targeting therapy is quite essential [21,22]. Therefore, drug delivery systems have drawn great attention in recent decades in oral infectious diseases. Drug delivery systems (DDS) are devices that can transport and release the therapeutic agents or bioactive substances to certain sites at certain rates in vivo [23,24], usually composed of the carriers and associated therapeutics [25]. They have been widely explored in biomedical research. With local drug administration and controlled drug release, DDS could provide higher curative efficiency and fewer side effects [23,26,27]. With all these advantages, DDS has been reported w...

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Development and In Vivo Evaluation of a Novel Histatin-5 Bioadhesive Hydrogel Formulation against Oral Candidiasis

Cited by 42 publications

References 44 publications

pH Dependent Antimicrobial Peptides and Proteins, Their Mechanisms of Action and Potential as Therapeutic Agents

pH Dependent Antimicrobial Peptides and Proteins, Their Mechanisms of Action and Potential as Therapeutic Agents

Candida albicans Pathogenesis: Fitting within the Host-Microbe Damage Response Framework

Emerging Applications of Drug Delivery Systems in Oral Infectious Diseases Prevention and Treatment

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