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Journal ArticleDOI

Potential therapeutic applications of biosurfactants

TL;DR: The current state-of-the-art in biosurfactant research for therapeutic purposes is covered, providing new directions towards the discovery and development of molecules with novel structures and diverse functions for advanced applications.
About: This article is published in Trends in Pharmacological Sciences.The article was published on 2013-12-01 and is currently open access. It has received 289 citations till now.

Summary (2 min read)

Biosurfactants as promising molecules

  • Biosurfactants comprise a group of diverse amphipathic molecules with distinct chemical structures produced by several microorganisms.
  • Likewise, these compounds can disrupt cell membranes that lead to cell lysis by increased membrane permeability and ultimately to leakage of metabolites [6] .
  • Among all properties of biosurfactants, their antibacterial, antifungal, and antiviral activities, in addition to their anti-adhesive character against pathogens, and probiotic nature, are the most relevant for health-related applications [1] [2] [3].
  • Their possible applications include gene transfection, as adjuvants for antigens, as inhibitors of fibrin clot formation, as activators of fibrin clot lysis, and also as antiadhesive coatings for biomaterials, incorporated into probiotic preparations to fight urogenital tract infections and for pulmonary immunotherapy [8] .
  • A liposome vector containing b-sitosterol b-D-glucoside biosurfactant-complexed DNA was successfully used for herpes simplex virus thymidine kinase gene therapy [14] .

Biosurfactants as antitumor agents

  • One of the most exciting findings that has been reported for biosurfactants is their ability to control a variety of mammalian cell functions and therefore their potential to act as antitumor agents interfering with some cancer progression processes (Table 1 ).
  • Furthermore, the authors demonstrated that MELs inhibited the activity of PKC in these cells.
  • The sophorolipid with one double bond in the fatty acid part had the strongest cytotoxic effect, whereas the antitumor activity of acidic sophorolipids was scarce.
  • Altogether, these results suggest that surfactin can downregulate the cell cycle and suppress cancer cell survival.
  • Finally, the ability of biosurfactants to disrupt cell membranes, leading to a sequence of events that include lysis, increased membrane permeability, and metabolite leakage, has also been suggested as a probable mechanism of antitumor activity [47] .

Biosurfactants as drug delivery agents

  • The discovery of new drugs and novel drug delivery systems (DDSs) with improved efficacies has made a significant impact on their ability to treat many types of diseases [48] .
  • Of these, the particulate type exists in a dispersed colloidal form with structures that include microspheres, nanoparticles, lipid particles, micelles, and vesicular systems such as liposomes, noisome, virosomes, and sphingosomes [49] .
  • Microemulsions have emerged as novel DDSs suitable for transdermal, topical, oral, nasal, ocular, intravenous, parenteral, and other routes of drug administration (reviewed in [48] ).
  • Systematic and preclinical studies are required before an optimal formulation can guarantee the safety and efficacy criteria for a given route of drug administration.
  • Several reasons have been reported for DDS failure, ranging from poor efficacy in delivering the drug to the drug precipitation due to dilution by biological fluids before reaching the target site.

Green molecules in drug formulation

  • In recent years, formulators have been actively seeking pharmaceutically acceptable excipients to design safer microemulsions.
  • Previous efforts have typically used synthetic hydrocarbon oils such as heptanes, dodecane, and cyclic oils such as cyclohexane, and surfactants with 12 carbon hydrophobic chains such as sodium dodecyl sulfate and tetraethylene glycol monododecyl ether, which are not approved for use in pharmaceutical formulations, and can present biocompatibility issues and exhibit some toxic effects [53] .
  • Similarly, natural surfactants have emerged as potential alternatives for their synthetic counterparts.
  • In particular, non-ionic surfactants such as sucrose esters, containing a hydrophilic sucrose group and fatty acid chains of varying degrees as a lipophilic group, have been widely employed in microemulsion formulation [56, 57] .
  • Biosurfactants have emerged as a better alternative to their synthetic counterparts.

Challenges, selection guidelines, and future prospects of biosurfactants in drug delivery applications

  • Data reported in the literature can drive the selection of the most appropriate oil/biosurfactant system.
  • Aggregation of surfactants in a lamellar arrangement can occur if one of the following requirements is met.
  • Furthermore, the high HLB value in the case of rhamnolipids indicates that a co-surfactant may often be required to alter the HLB value leading to microemulsion formation.
  • Taking a cue from these developments, microemulsions can be designed based on a cautious combination of an oil phase and a suitable biosurfactant.
  • Biosurfactants, in addition to their imminent potential for application in microemulsion-based drug formulations, have also been reported for use in triggered and targeted drug delivery.

Concluding remarks

  • Lipopeptide, glycolipid, and other types of biosurfactants, owing to their structural novelty and diverse biophysical properties, have recently emerged as possible broadspectrum agents for cancer chemotherapy/biotherapy and as safe vehicles or ingredients in drug delivery formulations.
  • Many new applications of these biomolecules have been suggested, mainly owing to their significant surface active properties that enable them to interact with cell membranes or surrounding environments to bring about the desired effect as a therapeutic molecule or as a part of a DDS.
  • A better understanding of the underpinning principles vis-a `-vis the mechanisms of actions at the molecular level would prompt researchers to develop a blueprint of the internal proceedings that can guide in conducting preclinical studies and clinical trials at a later stage.
  • Moreover, hemolytic activity of most of the For surfactin, it is only a suggestive value based on its ability to reduce surface tension to 27.2 mN/m. b Area for empirical CPP calculation is considered as 147 A ˚2 for surfactin [62] and 80 A ˚2 for rhamnolipid [59] .
  • Nevertheless, some biosurfactants have proven their efficacy in cosmetic and antibiotic formulations and additionally fulfilled the requirements of the drug regulatory bodies worldwide for biocompatible and nontoxic excipients, thus paving the way for the successful implementation of these molecules in drug delivery formulations.

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Citations
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Journal ArticleDOI
TL;DR: All the three families of Bacillus lipopeptides, namely, Surfactins, Iturins and Fengycins, have been explored for their antagonistic activities towards a wide range of phytopathogens including bacteria, fungi, and oomycetes.
Abstract: A lot of crops are destroyed by the phytopathogens such as fungi, bacteria, and yeast leading to economic losses to the farmers. Members of the Bacillus genus are considered as the factories for the production of biologically active molecules that are potential inhibitors of growth of phytopathogens. Plant diseases constitute an emerging threat to global food security. Many of the currently available antimicrobial agents for agriculture are highly toxic and nonbiodegradable and thus cause extended environmental pollution. Moreover, an increasing number of phytopathogens have developed resistance to antimicrobial agents. The lipopeptides have been tried as potent versatile weapons to deal with a variety of phytopathogens. All the three families of Bacillus lipopeptides, namely, Surfactins, Iturins and Fengycins, have been explored for their antagonistic activities towards a wide range of phytopathogens including bacteria, fungi, and oomycetes. Iturin and Fengycin have antifungal activities, while Surfactin has broad range of potent antibacterial activities and this has also been used as larvicidal agent. Interestingly, lipopeptides being the molecules of biological origin are environmentally acceptable.

313 citations


Cites background from "Potential therapeutic applications ..."

  • ...Lipopeptides as biosurfactants have been used in biomedical and pharmaceutical applications as antimicrobial, antimycoplasma, antiadhesive, and antitumor agents [41]....

    [...]

Journal ArticleDOI
TL;DR: This review highlights the relationships between biosurfactant molecular composition, structure, and their interfacial behavior and describes how environmental factors such as temperature, pH, and ionic strength can impact physicochemical properties and self-assembly behavior of biosurFactant-containing solutions and dispersions.

241 citations

Journal ArticleDOI
TL;DR: Understanding the natural function of these structurally diverse lipopeptides in Bacillus provides insight into microbial regulatory programs and is required for efficient development of more effective products.
Abstract: The lipopeptides of Bacillus are small metabolites that contain a cyclic structure formed by 7-10 amino acids (including 2-4 D-amino acids) and a beta-hydroxy fatty acid with 13-19 C atoms. These lipopeptides exhibit a variety of biological activities, including interactions with biofilms, and anti-fungal, anti-inflammatory, anti-tumor, anti-virus, and anti-platelet properties. The multiple activities of lipopeptides have stimulated significant interest in the exploitation of these lipopeptides for use as antibiotics, feed additives, anti-tumor agents, urgent thrombolytic therapeutic agents, and drug delivery systems. Understanding the natural function of these structurally diverse lipopeptides in Bacillus provides insight into microbial regulatory programs and is required for efficient development of more effective products. Currently, there is still insufficient knowledge of the direct target of these lipopeptides, and continued efforts are needed to enhance their biosynthesis efficiency for industrial applications.

199 citations


Cites background from "Potential therapeutic applications ..."

  • ...Biosurfactants may be a better alternative to their synthetic counterparts, and the recent trend in their use as templates for nanoparticle synthesis indicates the growing attractiveness of biosurfactants as greener replacements to their synthetic counter parts (Gudiña et al. 2013)....

    [...]

Journal ArticleDOI
TL;DR: Various microbial sources of biosurfactants and the current trends in terms of agricultural and biomedical applications are focused on.
Abstract: Synthetic surfactants are becoming increasingly unpopular in many applications due to previously disregarded effects on biological systems and this has led to a new focus on replacing such products with biosurfactants that are biodegradable and produced from renewal resources. Microbially derived biosurfactants have been investigated in numerous studies in areas including: increasing feed digestibility in an agricultural context, improving seed protection and fertility, plant pathogen control, antimicrobial activity, antibiofilm activity, wound healing and dermatological care, improved oral cavity care, drug delivery systems and anticancer treatments. The development of the potential of biosurfactants has been hindered somewhat by the myriad of approaches taken in their investigations, the focus on pathogens as source species and the costs associated with large-scale production. Here, we focus on various microbial sources of biosurfactants and the current trends in terms of agricultural and biomedical applications.

190 citations


Cites background from "Potential therapeutic applications ..."

  • ...However, some studies have shown that LPs and glycolipids can selectively inhibit the proliferation of cancer cells and disrupt cell membranes causing their lysis through apoptosis pathways (Gudi~na et al. 2013)....

    [...]

  • ...Furthermore, deformation of cells and loss of cell membrane integrity have been reported as the mechanisms of antimicrobial activity of many biosurfactants (Gudi~na et al. 2013)....

    [...]

Journal ArticleDOI
TL;DR: The biosurfactant exhibited a good performance in oil recovery assays when compared with chemical surfactants, which suggests its possible application in microbial enhanced oil recovery or bioremediation.
Abstract: In this work, biosurfactant production by Bacillus subtilis #573 was evaluated using corn steep liquor (CSL) as culture medium The best results were obtained in a culture medium consisting of 10% (v/v) of CSL, with a biosurfactant production of about 13 g/l To the best of our knowledge, this is the first report describing biosurfactant production by B subtilis using CSL as culture medium Subsequently, the effect of different metals (iron, manganese and magnesium) on biosurfactant production was evaluated using the medium CSL 10% It was found that for all the metals tested, the biosurfactant production was increased (up to 41, 44 and 35 g/l for iron, manganese and magnesium, respectively) When the culture medium was supplemented with the optimum concentration of the three metals simultaneously, the biosurfactant production was increased up to 48 g/l Furthermore, the biosurfactant exhibited a good performance in oil recovery assays when compared with chemical surfactants, which suggests its possible application in microbial enhanced oil recovery or bioremediation

171 citations

References
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Journal ArticleDOI
TL;DR: The use of microemulsions and closely related microemulsion-based systems as drug delivery vehicles is reviewed, with particular emphasis being placed on recent developments and future directions.

1,777 citations

Journal ArticleDOI
TL;DR: This review gives a detailed overview of the versatile functions of lipopeptides in the biology of Pseudomonas and Bacillus species, and highlights their role in competitive interactions with coexisting organisms, including bacteria, fungi, oomycetes, protozoa, nematodes and plants.
Abstract: Lipopeptides constitute a structurally diverse group of metabolites produced by various bacterial and fungal genera. In the past decades, research on lipopeptides has been fueled by their antimicrobial, antitumour, immunosuppressant and surfactant activities. However, the natural functions of lipopeptides in the lifestyles of the producing microorganisms have received considerably less attention. The substantial structural diversity of lipopeptides suggests that these metabolites have different natural roles, some of which may be unique to the biology of the producing organism. This review gives a detailed overview of the versatile functions of lipopeptides in the biology of Pseudomonas and Bacillus species, and highlights their role in competitive interactions with coexisting organisms, including bacteria, fungi, oomycetes, protozoa, nematodes and plants. Their functions in cell motility, leading to colonization of novel habitats, and in the formation and development of highly structured biofilms are discussed in detail. Finally, this review provides an update on lipopeptide detection and discovery as well as on novel regulatory mechanisms and genes involved in lipopeptide biosynthesis in these two bacterial genera.

909 citations

Journal ArticleDOI
TL;DR: Biosurfactants utility as suitable anti-adhesive coating agents for medical insertional materials leading to a reduction in a large number of hospital infections without the use of synthetic drugs and chemicals is indicated.
Abstract: The use and potential commercial application of biosurfactants in the medical field has increased during the past decade. Their antibacterial, antifungal and antiviral activities make them relevant molecules for applications in combating many diseases and as therapeutic agents. In addition, their role as anti-adhesive agents against several pathogens indicates their utility as suitable anti-adhesive coating agents for medical insertional materials leading to a reduction in a large number of hospital infections without the use of synthetic drugs and chemicals. This review looks at medicinal and therapeutic perspectives on biosurfactant applications.

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TL;DR: Global analysis of metabolites, such as by mass spectrometry and high-resolution 1H nuclear magnetic resonance spectroscopy, can be used to define the metabolic phenotype of cells, tissues or organisms.
Abstract: In the post-genomic era, several profiling tools have been developed to provide a more comprehensive picture of tumour development and progression. The global analysis of metabolites, such as by mass spectrometry and high-resolution 1H nuclear magnetic resonance spectroscopy, can be used to define the metabolic phenotype of cells, tissues or organisms. These 'metabolomic' approaches are providing important information about tumorigenesis, revealing new therapeutic targets and will be an important component of automated diagnosis.

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TL;DR: Biosurfactants play an essential natural role in the swarming motility of microorganisms and participate in cellular physiological processes of signaling and differentiation as well as in biofilm formation.

449 citations

Frequently Asked Questions (19)
Q1. What are the contributions mentioned in the paper "Potential therapeutic applications of biosurfactants" ?

This review covers the current state-ofthe-art in biosurfactant research for therapeutic purposes, providing new directions towards the discovery and development of molecules with novel structures and diverse functions for advanced applications. 

Despite the ever increasing demand of biosurfactants for commercial applications, their use in drug delivery requires further research on the interactions between the different components in microemulsions. 

For instance, biosurfactants could be used to influence the activity of sphingolipids, because these lipids emerged as effector molecules, which control various aspects of cell growth, proliferation, and anticancer therapeutics [46]. 

Lipid composition determines the structure, function, and integrity of biological membranes, and phosphatidylcholine (PC) and sphingomyelin (SM), in particular, play a role in stabilizing the bilayer structure. 

the important criterion that most formulations fail to abide is the judicious use of biocompatible and biodegradable pharmaceutical agents as their ingredients. 

these mixed systems may reduce the costs associated with the exclusive use of biosurfactants and could also encourage the development of a more efficient mixture. 

a sequence of apoptotic events was observed including the condensation of chromatin and DNA fragmentation, thus confirming the apoptosis-inducing potential of MELs in these cells [10]. 

Owing to the lack of systematic studies on the characteristics of biosurfactant microemulsion systems, such as phase behavior and its stability under different physicochemical conditions and compatibility of oil and co-surfactants, drug delivery applications of biosurfactants remain to be developed. 

hemolytic activity of most of thereported biosurfactants and the scarcity of clinical data on the use and validation of such molecules in animal models and human volunteers pose a major challenge in preparing safe drug delivery formulations. 

This study also indicated that surfactin-containing liposomes with theirhigher biocompatibility may improve the specific silencing of the gene of interest, that is, a more efficient delivery system led to an increase of the cellular uptake of siRNA, thus increasing the specific knockdown effect. 

The sophorolipid with one double bond in the fatty acid part had the strongest cytotoxic effect, whereas the antitumor activity of acidic sophorolipids was scarce. 

As previously mentioned, some surfactant molecules in aqueous solution are spontaneously transformed from micelles into a lamellar arrangement in the presence of a high salt concentration. 

Previous efforts have typically used synthetic hydrocarbon oils such as heptanes, dodecane, and cyclic oils such as cyclohexane, and surfactants with 12 carbon hydrophobic chains such as sodium dodecyl sulfate and tetraethylene glycol monododecyl ether, which are not approved for use in pharmaceutical formulations, and can present biocompatibility issues and exhibit some toxic effects [53]. 

MELs have been shown to induce the differentiation of human promyelocytic leukemia HL60 cells towards granulocytes [18]. 

Because there is an enormous diversity of microbial surfactants, new molecules with interesting antitumor activities are continuously being reported. 

This study showed that excess of sodium ions influenced the phase behavior of the system by minimizingelectrostatic repulsions between the charged head groups. 

most studies use a single cancer cell line to assess the cytotoxicity of the biosurfactants without using proper controls (e.g., normal cell lines), which means that these compounds may not be as specific as desired, and by contrast may be only effective against that single cell line. 

To accomplish these two essential purposes, different types of pharmaceutical carriers such as polymeric, particulate, macromolecular, and cellular carriers have been tested and are currently used. 

This report suggests that regulation of the activity of protein kinase C (PKC) might be associated with apoptosis induced by MELs.