Pullulan in pharmaceutical and cosmeceutical formulations: A review.

Pullulan, an α-glucan polysaccharide, is colorless, odorless, non-toxic, non-carcinogenic, highly biocompatible, edible and biodegradable in nature. The long chains of glucopyranose rings in pullulan structure are linked together by α-(1 â†’ 4) and α-(1 â†’ 6) glycosidic linkages. The occurrence of both glycosidic linkages in the pullulan structure contributes to its distinctive properties. The unique structure of pullulan makes it a potent candidate for both pharmaceutical and cosmeceutical applications. In pharmaceuticals, it can be used as a drug carrier and in various dosage formulations. It has been widely used in drug targeting, implants, ocular dosage forms, topical formulations, oral dosage forms, and oral liquid formulations, etc. Pullulan can be used as a potential carrier of active ingredients and their site-specific delivery to skin layers for cosmeceutical applications. It has been extensively used in cosmeceutical formulations like creams, shampoo, lotions, sunscreen, facial packs, etc. The current review highlights applications of pullulan in pharmaceutical and cosmeceutical applications.

Assessing the viability of carbamoylethyl pullulan-g-stearic acid based smart polymeric micelles for tumor targeting of raloxifene.

The present investigation entails the synthesis of smart pullulan polymeric micelles for evaluating its tumor targeting potential. For this purpose, two step polymerization synthesis reactions were conducted. In the first step, carbamoylethylation occurs by reaction of the free alcoholic moieties at 6th position of glucopyranose unit of pullulan with acrylamide in presence of alkali to obtain carbamoylethyl pullulan (CmP). In the second step, CmP undergoes graft polymerization with stearic acid (SA) to obtain CmP-g-stearic acid diblock co-polymer (CmP-g-SA) as evident from FTIR and NMR analysis. The XpRD spectra showed crystalline nature that was further confirmed by SEM indicating rough and poly-porous morphology. The QbD based optimized formulations of raloxifene HCl (RLX) loaded polymeric micelles (RLX PMs) exhibited pH-dependent release profile with added advantage of 1.2 times reduction in percentage hemolysis giving substantial compatibility with erythrocytes. In vivo pharmacokinetic performance of RLX PMs suggested enhanced mean residence time and volume of distribution. Besides, the biodistribution study of RLX PMs manifested enhanced entry of RLX in mammary carcinoma tissues as compared to normal tissues suggested that CmP-g-SA based micelles enhanced the anti-tumor activity of RLX. Overall, the findings pointed toward the biocompatibility of CmP-g-SA as a potential carrier system for the delivery of RLX.

Pullulan in biomedical research and development - A review.

Pullulan is an imperative microbial exo-polymer commercially produced by yeast like fungus Aureobasidium pullulans. Its structure contains maltosyl repeating units which comprises two α-(1 â†’ 4) linked glucopyranose rings attached to one glucopyranose ring through α-(1 â†’ 6) glycosidic bond. The co-existence of α-(1 â†’ 6) and α-(1 â†’ 4) glycosidic linkages endows distinctive physico-chemical properties to pullulan. It is highly biocompatible, non-toxic and non-carcinogenic in nature. It is extremely resistant to any mutagenicity or immunogenicity. The unique properties of pullulan make it a potent candidate for biomedical applications viz. drug delivery, gene delivery, tissue engineering, molecular chaperon, plasma expander, vaccination, etc. This review highlights the potential of pullulan in biomedical research and development.

Mushroom lectins in biomedical research and development.

Lectins are unique biorecognition proteins which recognize and interact with various cell surface carbohydrates/glycoproteins. These ubiquitous molecules are involved in various cell-cell interactions and can be exploited to analyze cell surface associated interactions and biological functions. Amongst fungi, lectins have been extensively explored from mushrooms as compared to microfungi or yeasts. Lectins from basidiomycetes have diverse features in terms of their physico-chemical characteristics and carbohydrate specificity. A plethora of lectins from genera Aleuria, Agrocybe, Boletus, Pleurotus, Russula, Schizophyllum, Volvariella, etc. exhibit potential applications in biomedical field. The current review summarizes the potential sources and characteristics of mushroom lectins. Potential involvement of mushroom lectin as anticancer, mitogenic, antiviral, antimicrobial, antioxidant and therapeutic agents has been discussed.

Structural aspects and biomedical applications of microfungal lectins.

Lectins are unique biorecognition molecules that identify cell surface carbohydrates/glycoproteins and play significant role in various interactions. They are ubiquitous glycan-specific proteins/glycoproteins of non-immune origin. Amongst microfungi, lectins have been widely reported from aspergilli, penicilli, Fusarium sp., etc., however a plethora of genera still remains unexplored. Microfungal lectins have wide diversity in their haemagglutination and carbohydrate specificity. They also exhibit great variations in their structural organization which influences lectin-glycan interactions. The present review summarizes the sources, characteristics and structural diversity of microfungal lectins. Prospective biomedical applications of microfungal lectins as anticancer, mitogenic, immunomodulatory, antioxidant and therapeutic agents have been discussed extensively.

Sequential statistical optimization of lactose-based medium and process variables for inulinase production from Penicillium oxalicum BGPUP-4.

A statistical tool of response surface methodology was used sequentially to optimise lactose-based medium and process variables for inulinase production from Penicillium oxalicum BGPUP-4. Two-level CCRD with four variables, for each design, was used for the optimization study. The independent variables: lactose 1-3%, NH4H2PO4 0.2-0.5%, NaNO3 0.2-0.5%, pH 5.0-7.0 (design-1); temperature 25-35 °C, incubation time 4.0-6.0 days, inoculum size 1.0-3.0 mycelial agar discs and agitation 100-200 rpm (design-2) were selected for the present investigation. The optimised medium variables (lactose 3.70%, NH4H2PO4 0.35%, NaNO3 0.35% and pH 6.0) produced 44.44 (IU/ml) and 0.38 (g dry wt./50 ml) of inulinase and biomass yield, respectively. Thereafter, the optimization of process conditions (temperature 25 °C, incubation time 5 days, inoculum size 2 mycelial agar discs and agitation 150 rpm), increased the inulinase production 50.45 (IU/ml) and biomass yield 0.26 (g dry wt./50 ml). The good agreement between experimental and predicted values in both the designs, the coefficient of determination (R2 ) greater than 0.90 and very close to 1.0 shows an appropriate fitness of the polynomial quadratic models.

Lectins from red algae and their biomedical potential.

Lectins are unique proteins or glycoproteins of non-immune origin that bind specifically to carbohydrates. They recognise and interact reversibly to either free carbohydrates or glycoconjugates, without modifying their structure. Lectins are highly diverse and widely distributed in nature and have been extensively reported from various red algae species. Numerous red algae species have been reported to possess lectins having carbohydrate specificity towards complex glycoproteins or high-mannose N-glycans. These lectin-glycan interactions further trigger many biochemical responses which lead to their extensive use as valuable tools in biomedical research. Thus, owing to their exceptional glycan recognition property, red algae lectins are potential candidate for inhibition of various viral diseases. Hence, the present report integrates existing information on the red algae lectins, their carbohydrate specificity, and characteristics of purified lectins. Further, the review also reports the current state of research into their anti-viral activity against various enveloped viruses such as HIV, hepatitis, influenza, encephalitis, coronavirus and herpes simplex virus and other biomedical activities such as anti-cancer, anti-microbial, anti-inflammatory, anti-nociceptive and acaricidal activities.

Pullulan: A novel molecule for biomedical applications.

Pullulan is an imperative natural polymer produced commercially by yeast like fungus Aureobasidium pullulans. It is non-toxic, non-immunogenic, non-carcinogenic and non-mutagenic in nature. The structure of pullulan consist unique linkage pattern with two α-(1→4) and one α-(1→6) glycosidic bonds in maltotriose repeating units (G3). Pullulan endows distinctive physical traits due to the presence of nine hydroxyl groups on glucopyranose rings of G3 units. It can be derivatized in various forms by substituting these hydroxyl groups to enhance its utility in biomedical applications. Pullulan and its derivatives are completely explored for their applications in food and pharmaceutical industries. Owing to these special properties, native pullulan and its derivatives possess potential application in multiple diagnostics. This review presents elaborated discussion on role of pullulan and its derivatives in various biomedical applications e.g. drug delivery, gene targeting, tissue engineering, vaccination, plasma substitution, chaperone-like activity, medical imaging, insulinotropic activity, pharmaceutical dosages formation, coating, etc.

Mushroom Lectins as Promising Anticancer Substances.

Lectins are proteins/glycoproteins of non-immune origin, which are widely distributed in nature. They have at least one non-catalytic domain, which binds reversibly to specific monosaccharides or oligosaccharides. Lectins recognizing sugar moieties in cell walls or cell membranes alter the membrane physiology and trigger biochemical changes in the cell. Thus, various applications of lectins have been described, for example as tools to identify aberrant glycans expressed by neoplastic cells and as antitumor agents by inducing apoptosis by various mechanisms. In order to widen applications of anti-tumor lectins, a detailed investigation of their action mechanism is required. Mushrooms are a valuable source of novel lectins with unique specificities and potentials for biotechnological and biomedical applications. This article reviews information on anti-proliferative activity of mushroom lectins obtained in-vitro and in-vivo. The possible role of lectins as cancer therapeutics is discussed together with the mechanisms underlying the anti-proliferative activity, which may help to exploit these biomolecules as potential novel antitumor drugs in near future.

Multifunctional iron bound lactoferrin and nanomedicinal approaches to enhance its bioactive functions.

Lactoferrin (Lf), an iron-binding protein from the transferrin family has been reported to have numerous functions. Even though Lf was first isolated from milk, it is also found in most exocrine secretions and in the secondary granules of neutrophils. Antimicrobial and anti-inflammatory activity reports on lactoferrin identified its significance in host defense against infection and extreme inflammation. Anticarcinogenic reports on lactoferrin make this protein even more valuable. This review is focused on the structural configuration of iron-containing and iron-free forms of lactoferrin obtained from different sources such as goat, camel and bovine. Apart for emphasizing on the specific beneficial properties of lactoferrin from each of these sources, the general antimicrobial, immunomodulatory and anticancer activities of lactoferrin are discussed here. Implementation of nanomedicinial strategies that enhance the bioactive function of lactoferrin are also discussed, along with information on lactoferrin in clinical trials.

Purification, characterization, and mitogenic potential of a mucin-specific mycelial lectin from Aspergillus sparsus.

Lectins are carbohydrate binding proteins or glycoproteins that bind reversibly to specific carbohydrates present on the apposing cells, which is responsible for their ability to agglutinate red blood cells, lymphocytes, fibroblasts, etc. Due to their carbohydrate specificity, lectins have been used for purification and characterization of glycoproteins like antibodies, cytokines, tumor-associated glycoproteins, hormones, inhibitors, growth factors, various enzymes, membrane proteins (receptors), or even toxins and viruses. In the present study, a mycelial lectin from Aspergillus sparsus was purified, characterized, and evaluated for its mitogenic potential. Lectin could be effectively purified 17.8-fold in a single-step using affinity chromatography on mucin-sepharose column. Lectin migrated as a single band in sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) with an apparent molecular mass of 100.2 kDa. Lectin showed pH optima of 6.5-8.0, and optimum temperature was determined to be 20-30 °C. Lectin was stable within a pH range of 5.5-10.0 and showed fairly good thermostability. Lectin activity was unaffected in the presence of EDTA, while activity reduced upon interaction with denaturants. MTT assay revealed strong mitogenic potential of A. sparsus lectin at a concentration up to 100 µg/ml.

Algal lectins as promising biomolecules for biomedical research.

Lectins are natural bioactive ubiquitous proteins or glycoproteins of non-immune response that bind reversibly to glycans of glycoproteins, glycolipids and polysaccharides possessing at least one non-catalytic domain causing agglutination. Some of them consist of several carbohydrate-binding domains which endow them with the properties of cell agglutination or precipitation of glycoconjugates. Lectins are rampant in nature from plants, animals and microorganisms. Among microorganisms, algae are the potent source of lectins with unique properties specifically from red algae. The demand of peculiar and neoteric biologically active substances has intensified the developments on isolation and biomedical applications of new algal lectins. Comprehensively, algal lectins are used in biomedical research for antiviral, antinociceptive, anti-inflammatory, anti-tumor activities, etc. and in pharmaceutics for the fabrication of cost-effective protein expression systems and nutraceutics. In this review, an attempt has been made to collate the information on various biomedical applications of algal lectins.

Immunomodulatory and therapeutic potential of a mycelial lectin from Aspergillus nidulans.

Lectins bind to surface receptors on target cells, and activate a cascade of events, eventually leading to altered immune status of host. The immunomodulatory potential of purified lectin from Aspergillus nidulans was evaluated in Swiss albino mice treated intraperitoneally with seven different doses of purified lectin. Lectin prevented BSA-induced Arthus reaction and systemic anaphylaxis. The enhanced functional ability of macrophages was evident from respiratory burst activity and nitric oxide production in splenocyte cultures. Interferon-gamma and interleukin-6 levels were significantly up-regulated in treated groups. Maximum stimulatory effect was observed at the dose of 1.5 mg/kg body weight. Therapeutic potential of A. nidulans lectin was assessed against trinitrobenzene sulfonic acid-induced ulcerative colitis in male Wistar rats. Rats pre-treated with 80 mg/kg body weight of purified lectin intraperitoneally prior to colitis induction showed lesser disease severity and recovery within 7 days, while rats post-treated with the same dose showed recovery in 11 days. The results demonstrate immunomodulatory effects of A. nidulans lectin in Swiss albino mice, resulting in improved immune status of the animals and unfold its curative effect against ulcerative colitis in rat model. This is the first report on immunomodulatory and therapeutic potential of a lectin from microfungi.

Enhanced exoinulinase production from Kluyveromyces marxianus YS-1 using response surface methodology

Optimization of critical medium components for exoinulinase production by Kluyveromyces marxianus YS-1 at shake-flask was investigated using response surface methodology (RSM) based on a central composite rotatable design (CCRD). A five-level with five factors CCRD was used to evaluate the influence of related factors including concentration of inulin, meat extract, calcium chloride, sodium dodecyl sulphate and medium pH. Optimum values obtained by RSM were 2 percent inulin, 2.17 percent meat extract, 0.65 mM calcium chloride, 0.10 mM sodium dodecyl sulphate and pH 5.5. Optimized medium projected a theoretical exoinulinase production of 63.61 IU/mL and biomass yield of 0.965 (OD600/10). Multiple correlation coefficient R was 0.9976 and 0.9605 for exoinulinase production and biomass yield, respectively, which being close to one, justified an excellent correlation between the predicted and experimental values. Maximum productivity of exoinulinase (64.05 IU/mL) obtained experimentally by RSM was more than double in comparison to earlier findings using classical one-variable-at-a-time technique.

Foi investigada a optimização de componentes criticos do meio de cultivo para a produção de exoinulinase por Kluyveromyces marxianus YS-1 em frascos agitados utilizando a metodologia de superficie de resposta (RSM), com base em um delineamento composto central rotativo. As variáveis independentes, com cinco niveis, foram as concentrações de inulina, de extrato de carne, de cloreto de cálcio e de dodecil sulfato de sódio, bem como o pH do meio de cultivo. Os valores ótimos, obtidos pela RSM, foram com 2 por cento de inulina, 2.17 por cento de extrato de carne, 0.65 mM de cloreto de cálcio, 0.10 mM de dodecil sulfato de sódio e pH 5.5. As estimativas de produção de exoinulinase e de rendimento em biomassa no meio otimizado foram de 63.61 UI/ml e de 9.65 (em termos de OD600/10), respectivamente. Os coeficientes de correlação múltipla R foram de 0.9976 e 0.9605 para produção de exoinulinase e biomassa, respectivamente, e, sendo próximos de um, indicam uma excelente correlação entre os valores estimados e experimentais. A máxima productividade de exoinulinase (64.05 UI/ml) obtida experimentalmente por RSM foi mais que o dobro em comparação com nossos resultados anteriores utilizando uma técnica de otimização clássica de uma variável por vez.

Mushroom lectins: current status and future perspectives.

Lectins are nonimmune proteins or glycoproteins that bind specifically to cell surface carbohydrates, culminating in cell agglutination. These are known to play key roles in host defense system and also in metastasis. Many new sources have been explored for the occurrence of lectins during the last few years. Numerous novel lectins with unique specificities and exploitable properties have been discovered. Mushrooms have attracted a number of researchers in food and pharmaceuticals. Many species have long been used in traditional Chinese medicines or functional foods in Japan and other Asian countries. A number of bioactive constituents have been isolated from mushrooms including polysaccharides, polysaccharopeptides, polysaccharide-protein complexes, proteases, ribonucleases, ribosome inactivating proteins, antifungal proteins, immunomodulatory proteins, enzymes, lectins, etc. Mushroom lectins are endowed with mitogenic, antiproliferative, antitumor, antiviral, and immune stimulating potential. In this review, an attempt has been made to collate the information on mushroom lectins, their blood group and sugar specificities, with an emphasis on their biomedical potential and future perspectives.