Current Medicinal Chemistry - Volume 26, Issue 14, 2019

Background: Cellulose being the first abundant biopolymers in nature has many fascinating properties, including low-cost, good biodegradability, and excellent biocompatibility, which made cellulose a real potential material to create nano-drug delivery systems (nano-DDS). This review aims to present and discuss some remarkable recent advances on the drug delivery applications of cellulosebased prodrugs and nanoparticles. Methods: By searching the research literatures over last decade, a variety featured studies on cellulosebased nano-DDS were summarized and divided into prodrugs, prodrug nanoparticles, solid or derivative nanopartilces, amphiphilic copolymer nanoparticles, and polyelectrolyte complex nanoparticles. Various methods employed for the functionalization, pharmacodynamic actions and applications were described and discussed. Results: Many types of cellulose-based nano-DDS can ensure efficient encapsulation of various drugs and then overcome the free drug molecule shortcomings. Among all the method described, cellulosebased amphiphilic nanoparticles are most frequently used. These formulations have the higher drug loading capability, a simple and flexible way to achieve multi-functional. Apart from hydrophilic or hydrophobic modification, cellulose or its derivatives can form nanoparticles with different small molecules and macromolecules, leading to a large spectrum of cellulose-based nano-DDS and providing some unexpected advantages. Conclusion: Thorough physicochemical characterization and profound understanding of interactions of the cellulose-based nano-DDS with cells and tissues is indispensable. Moreover, studies toward technics parameter optimization and scale up from the laboratory to production level should be undertaken. The development of intravenous and orally applicable cellulose-based nano-DDS will be an important research area, and these systems will have more commercial status in the market.

Background: Due to the non-toxicity, abundance and biodegradability, recently more and more attention has been focused on the exploration of hemicellulose as the potential substrate for the production of liquid fuels and other value-added chemicals and materials in different fields. This review aims to summarize the current knowledge on the promising application of nature hemicellulose and its derivative products including its degradation products, its new derivatives and hemicellulosebased medical biodegradable materials in the medical and pharmaceutical field, especially for inmmune regulation, bacteria inhibition, drug release, anti-caries, scaffold materials and anti-tumor. Methods: We searched the related papers about the medical and pharmaceutical application of hemicellulose and its derivative products, and summarized their preparation methods, properties and use effects. Results: Two hundred and twenty-seven papers were included in this review. Forty-seven papers introduced the extraction and application in immune regulation of nature hemicellulose, such as xylan, mannan, xyloglucan (XG) and β-glucan. Seventy-seven papers mentioned the preparation and application of degradation products of hemicellulose for adjusting intestinal function, maintaining blood glucose levels, enhancing the immunity and alleviating human fatigue fields such as xylooligosaccharides, xylitol, xylose, arabinose, etc. The preparation of hemicellulose derivatives were described in thirty-two papers such as hemicellulose esters, hemicellulose ethers and their effects on anticoagulants, adsorption of creatinine, the addition of immune cells and the inhibition of harmful bacteria. Finally, the preparations of hemicellulose-based materials such as hydrogels and membrane for the field of drug release, cell immobilization, cancer therapy and wound dressings were presented using fifty-five papers. Conclusion: The structure of hemicellulose-based products has the significant impact on properties and the use effect for the immunity, and treating various diseases of human. However, some efforts should be made to explore and improve the properties of hemicellulose-based products and design the new materials to broaden hemicellulose applications.

The pertinent issue of resources shortage arising from global climate change in the recent years has accentuated the importance of materials that are environmentally friendly. Despite the merits of current material like cellulose as the most abundant natural polysaccharide on earth, the incorporation of lignocellulosic biomass has the potential to value-add the recent development of cellulose-derivatives in drug delivery systems. Lignocellulosic biomass, with a hierarchical structure is comprised of cellulose, hemicellulose and lignin. As an excellent substrate that is renewable, biodegradable, biocompatible and chemically accessible for modified materials, lignocellulosic biomass sets forth a myriad of applications. To date, materials derived from lignocellulosic biomass have been extensively explored for new technological development and applications, such as biomedical, green electronics and energy products. In this review, chemical constituents of lignocellulosic biomass are first discussed before we critically examine the potential alternatives in the field of biomedical application. In addition, the pretreatment methods for extracting cellulose, hemicellulose and lignin from lignocellulosic biomass as well as their biological applications including drug delivery, biosensor, tissue engineering etc. are reviewed. It is anticipated there will be an increasing interest and research findings in cellulose, hemicellulose and lignin from natural resources, which help provide important directions for the development in biomedical applications.

Lignocellulose is the most abundant renewable natural resource on earth and has been successfully used for the production of biofuels. A significant challenge is to develop cost-effective, environmentally friendly and efficient processes for the conversion of lignocellulose materials into suitable substrates for biotransformation. A number of approaches have been explored to convert lignocellulose into sugars, e.g. combining chemical pretreatment and enzymatic hydrolysis. In nature, there are organisms that can transform the complex lignocellulose efficiently, such as wood-degrading fungi (brown rot and white rot fungi), bacteria (e.g. Clostridium thermocellum), arthropods (e.g. termite) and certain animals (e.g. ruminant). Here, we highlight recent case studies of the natural degraders and the mechanisms involved, providing new utilities in biotechnology. The sugars produced from such biotransformations can be used in metabolic engineering and synthetic biology for the complete biosynthesis of natural medicine. The unique opportunities in using lignocellulose directly to produce natural drug molecules with either using mushroom and/or ‘industrial workhorse’ organisms (Escherichia coli and Saccharomyces cerevisiae) will be discussed.

Bio-compatible, bio-degradable, and bio-available excipients are of critical interest for drug delivery systems. Cellulose and its derivative-based excipients have been well studied due to their green/natural and unique encapsulation/binding properties. They are often used in controlled/sustained drug delivery systems. In these applications, cellulose and its derivatives function generally can modify the solubility/gelling behavior of drugs, resulting in different mechanisms for controlling the release profiles of drugs. In this paper, the current knowledge in the structure and chemistry of conventional cellulose derivatives, and their applications in drug delivery systems are briefly reviewed. The development of innovative cellulose-based materials, including micro-cellulose (MC) and nano-cellulose (NC) in the applications of sustained drug delivery, is also discussed.

The development of innovative drug delivery systems, versatile to different drug characteristics with better effectiveness and safety, has always been in high demand. Chitosan, an aminopolysaccharide, derived from natural chitin biomass, has received much attention as one of the emerging pharmaceutical excipients and drug delivery entities. Chitosan and its derivatives can be used for direct compression tablets, as disintegrant for controlled release or for improving dissolution. Chitosan has been reported for use in drug delivery system to produce drugs with enhanced muco-adhesiveness, permeation, absorption and bioavailability. Due to filmogenic and ionic properties of chitosan and its derivative(s), drug release mechanism using microsphere technology in hydrogel formulation is particularly relevant to pharmaceutical product development. This review highlights the suitability and future of chitosan in drug delivery with special attention to drug loading and release from chitosan based hydrogels. Extensive studies on the favorable non-toxicity, biocompatibility, biodegradability, solubility and molecular weight variation have made this polymer an attractive candidate for developing novel drug delivery systems including various advanced therapeutic applications such as gene delivery, DNA based drugs, organ specific drug carrier, cancer drug carrier, etc.

Candida is the main human fungal pathogen causing infections (candidiasis), mostly in the elderly and immunocompromised hosts. Even though Candida spp. is a member of the oral microbiota in symbiosis, in some circumstances, it can cause microbial imbalance leading to dysbiosis, resulting in oral diseases. Alternative therapies are urgently needed to treat oral candidiasis (usually associated to biofilms), as several antifungal drugs’ activity has been compromised. This has occurred especially due to an increasing occurrence of drugresistant in Candida spp. strains. The overuse of antifungal medications, systemic toxicity, cross-reactivity with other drugs and a presently low number of drug molecules with antifungal activity, have contributed to important clinical limitations. We undertook a structured search of bibliographic databases (PubMed Central, Elsevier’s ScienceDirect, SCOPUS and Springer’s SpringerLink) for peer-reviewed research literature using a focused review in the areas of alternatives to manage oral candidiasis. The keywords used were “candidiasis”, “oral candidiasis”, “biofilm + candida”, “alternative treatment”, “combination therapy + candida” and the reports from the last 10 to 15 years were considered for this review. This review identified several promising new approaches in the treatment of oral candidiasis: combination anti-Candida therapies, denture cleansers, mouth rinses as alternatives for disrupting candidal biofilms, natural compounds (e.g. honey, probiotics, plant extracts and essential oils) and photodynamic therapy. The findings of this review confirm the importance and the urgency of the development of efficacious therapies for oral candidal infections.

Biofilms are the predominant mode of microbial growth and it is now fully accepted that a majority of infections in humans are associated with a biofilm etiology. Biofilms are defined as attached and structured microbial communities surrounded by a protective exopolymeric matrix. Importantly, sessile microorganisms growing within a biofilm are highly resistant to antimicrobial agents. Thus, there is an urgent need to develop new and improved anti-biofilm therapies. Unfortunately, most of the current techniques for in-vitro biofilm formation are not compatible with high throughput screening techniques that can speed up discovery of new drugs with anti-biofilm activity. To try to overcome this major impediment, our group has developed a novel technique consisting of micro-scale culture of microbial biofilms on a microarray platform. Using this technique, hundreds to thousands of microbial biofilms, each with a volume of approximately 30-50 nanolitres, can be simultaneously formed on a standard microscope slide. Despite more than three orders of magnitude of miniaturization over conventional biofilms, these nanobiofilms display similar growth, structural and phenotypic properties, including antibiotic drug resistance. These nanobiofilm chips are amenable to automation, drastically reducing assay volume and costs. This technique platform allows for true high-throughput screening in search for new anti-biofilm drugs.

Flavonoids are polyphenolic compounds with already confirmed various health benefits. This review will shed light on flavonoids as potential antifungals in Candida albicans infections. C. albicans is an opportunistic pathogen able to cause serious health issues due to numerous virulence factors amplifying its pathogenicity. One of the most important virulence factors is Candida ability to form biofilms which are highly resistant to the treatment of antifungal drugs; making diminishing of this pathogen even more challenging. This review will focus on current knowledge on individual flavonoid compounds having the potential to deal with C. albicans in vitro, with special turn on antibiofilm potential and insight into the mode of action, where available. Majority of the commercial drugs for the treatment of candidiasis belong to azole class, so the activity of flavonoids will be compared with the activity of newly synthetized azole compounds, as well as with azole drugs that are already on the market as official therapeutics. This literature review will provide pros and cons for pushing future research towards exploring novel synthetic azoles or further examination of a wide pallet of natural flavonoids.