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The objective of this review is to provide an up-to-date and all-encompassing account of the recent advancements in the domain of interactive wound dressings. Considering the gap between the achieved and desired clinical outcomes with currently available or under-study wound healing therapies, newer more specific options based on the wound type and healing phase are reviewed. Starting from the comprehensive description of the wound healing process, a detailed classification of wound dressings is presented. Subsequently, we present an elaborate and significant discussion describing interactive (unconventional) wound dressings. Latter includes biopolymer-based, bioactive-containing and biosensor-based smart dressings, which are discussed in separate sections together with their applications and limitations. Moreover, recent (2-5 years) clinical trials, patents on unconventional dressings, marketed products, and other information on advanced wound care designs and techniques are discussed. Subsequently, the future research direction is highlighted, describing peptides, proteins, and human amniotic membranes as potential wound dressings. Finally, we conclude that this field needs further development and offers scope for integrating information on the healing process with newer technologies.
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Vendajes , Cicatrización de Heridas , Humanos , Cicatrización de Heridas/efectos de los fármacos , Animales , Materiales Biocompatibles/químicaRESUMEN
Sesamol, a lignan, obtained from sesame seeds (Sesamum indicum Linn., Pedaliaciae) has a promising antioxidant, and anti-inflammatory profile. When applied topically, free sesamol rapidly crosses skin layers and gets absorbed in systemic circulation. Its encapsulation into solid lipid nanoparticles not only improved its localised delivery to skin but also resulted in better skin retention, as found in ex-vivo skin retention studies. Free and encapsulated sesamol was compared for antimicrobial and antibiofilm activity against some common skin pathogens and it was found that encapsulation improved the antimicrobial profile by 200%. In vivo evaluation in diabetic open excision wound model suggested that encapsulation of sesamol in SLNs substantially enhanced its wound healing potential when investigated for biophysical, biochemical and histological parameters. It was envisaged that this was achieved via inhibiting bacterial growth and clearing the bacterial biofilm at the wound site, and by regulating oxidative stress in skin tissue.
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Antiinfecciosos , Liposomas , Nanopartículas , Fenoles , Benzodioxoles/farmacología , Cicatrización de HeridasRESUMEN
The current study describes a suppository base composed of aqueous gelatin solution emulsifying oil globules with probiotic cells dispersed within. The favorable mechanical properties of gelatin to provide a solid gelled structure, and the tendency of its proteins to unravel into long strings that interlace when cooled, lead to a three-dimensional structure that can trap a lot of liquid, which was exploited herein to result in a promising suppository form. The latter maintained incorporated probiotic spores of Bacillus coagulans Unique IS-2 in a viable but non-germinating form, preventing spoilage during storage and imparting protection against the growth of any other contaminating organism (self-preserved formulation). The gelatin-oil-probiotic suppository showed uniformity in weight and probiotic content (23 ± 2.481 × 108 cfu) with favorable swelling (double) followed by erosion and complete dissolution within 6 h of administration, leading to the release of probiotic (within 45 min) from the matrix into simulated vaginal fluid. Microscopic images indicated presence of probiotics and oil globules enmeshed in the gelatin network. High viability (24.3 ± 0.46 × 108), germination upon application and a self-preserving nature were attributed to the optimum water activity (0.593 aw) of the developed composition. The retention of suppositories, germination of probiotics and their in vivo efficacy and safety in vulvovaginal candidiasis murine model are also reported.
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Encapsulation techniques and materials, explored for addressing compromised probiotic gut survival, report significant production losses resulting in <10% entrapment. Presently, we report three-time enhanced entrapment (30 ± 1.2%) of Lactobacillus acidophilus (LAB) in calcium-alginate beads, by modifying process parameters and employing polyethylene glycol (PEG). Water-loving, viscolysing and osmotic-building effects of PEG create numerous, fine voids in the alginate gel allowing efficient diffusion of crosslinking calcium ions, resulting in less leaky beads. Eudragit S100 overcoat improved LAB survival by 690 times in simulated GIT stresses.In DMH-DSS induced colitis and precancerous lesions in rats, while free LAB failed to show any protection, pharmabiotic beads significantly (p < .05) reduced lipid peroxidation, increased antioxidant levels; decreased serum inflammatory burden; downregulated COX-2, iNOS, and c-Myc expression; elevated levels of the selected gut bacteria and SCFAs especially butyrate, all of which add up to antioxidant, anti-inflammatory, balanced gut biota, and ultimately anticancer effects.
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Colitis/tratamiento farmacológico , Microbioma Gastrointestinal/efectos de los fármacos , Lactobacillus acidophilus , Probióticos/farmacología , Tecnología Farmacéutica/métodos , Alginatos/química , Animales , Antioxidantes/metabolismo , Modelos Animales de Enfermedad , Mediadores de Inflamación/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Masculino , Polietilenglicoles/química , Ácidos Polimetacrílicos/química , Ratas , Ratas WistarRESUMEN
BACKGROUND: Solid free forming (SFF) technique also called additive manufacturing process is immensely popular for biofabrication owing to its high accuracy, precision and reproducibility. METHOD: SFF techniques like stereolithography, selective laser sintering, fused deposition modeling, extrusion printing, and inkjet printing create three dimension (3D) structures by layer by layer processing of the material. To achieve desirable results, selection of the appropriate technique is an important aspect and it is based on the nature of biomaterial or bioink to be processed. RESULT & CONCLUSION: Alginate is a commonly employed bioink in biofabrication process, attributable to its nontoxic, biodegradable and biocompatible nature; low cost; and tendency to form hydrogel under mild conditions. Furthermore, control on its rheological properties like viscosity and shear thinning, makes this natural anionic polymer an appropriate candidate for many of the SFF techniques. It is endeavoured in the present review to highlight the status of alginate as bioink in various SFF techniques.
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Alginatos/química , Materiales Biocompatibles , Hidrogeles , Phaeophyceae/química , Impresión Tridimensional , Reproducibilidad de los ResultadosRESUMEN
Aim of the study was to evaluate a combination of ginger extract (GE; antioxidant, anti-inflammatory) and Lactobacillus acidophilus (LAB; probiotic), in DMH-DSS-induced inflammation-driven colon cancer, in Wistar rats. Effect of varying GE concentration on growth of LAB was assessed in vitro. Colonic histology and permeability, oxidative stress, serum proinflammatory cytokines, expression of selected genes, gut bacteria, and SCFA determination of gut content was monitored after treatment with agents alone or in combination, postdisease induction. Significant increase in LAB CFU was observed following 48 and 96 hr of incubation with GE; 0.4% w/v GE showed the best results and was used in the cobiotic. Cobiotic administration significantly reversed the DMH-DSS-induced colonic histological alterations. Significant (p < .05) reduction in lipid peroxidation and increase in antioxidant levels (catalase and SOD) was observed in cobiotic group, whereas individual agents did not show any effect. Restoration of colonic permeability, decrease in serum inflammatory burden, and downregulation of COX-2, iNOS, and c-Myc expression on treatment with cobiotic was significantly (p < .05) better than individual agents. Neither LAB nor cobiotic administration produced any change in gut bacteria nor SCFA levels, probably due to loss of LAB viability under adverse gut conditions. Study concludes that presented cobiotic has a promising therapeutic potential, which can be improved by a smartly designed formulation.
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Inflamación/tratamiento farmacológico , Lactobacillus acidophilus , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/farmacología , Probióticos , Zingiber officinale/química , Animales , Antiinflamatorios/farmacología , Antioxidantes/metabolismo , Carcinógenos , Neoplasias del Colon/tratamiento farmacológico , Ciclooxigenasa 2/metabolismo , Regulación hacia Abajo , Interleucina-6/sangre , Masculino , Óxido Nítrico Sintasa de Tipo II/metabolismo , Proteínas Proto-Oncogénicas c-myc/metabolismo , Ratas , Ratas Wistar , Factor de Necrosis Tumoral alfa/sangreRESUMEN
Presently, we explore a cobiotic-ginger extract (GE; antioxidant-antiinflammatory) and Lactobacillus acidophilus (LAB, probiotic), for control of oxidative-stress, inflammation and dysbiosis mediated gut ailments. Since orally administered LAB looses viability while GE is a gastric irritant with poor ADME, we encapsulated them into calcium-alginate beads. Water-loving, viscolysing, and osmotic-building effects of polyethylene glycol were used to address poor probiotic encapsulation (≤10%) by effective sealing of numerous fine voids formed in the alginate gel. Beads were systematically optimized for maximum entrapment (92±2.3% for GE, and 30±1.2% for LAB) and sustained release, and were coated with eudragit-S100 for colonic-targetability, as established by in-vitro release. In-vivo evaluation in DMH-DSS induced colitis and precancerous lesions, in rats, indicated attenuation of oxidative stress (catalase, SOD, LPO) and inflammatory burden (IL-6 and TNF-α), and downregulation of COX-2, iNOS, and c-Myc by both GE and LAB; restoration of colonic permeability by GE; and modulation of gut bacteria and SCFAs by LAB as the mechanisms of action. Complementing activities of GE and LAB in cobiotic beads lead to better reversals. Histology (H&E and toluidine blue) confirmed healing of precancerous lesions.
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Alginatos/química , Colon/efectos de los fármacos , Colon/microbiología , Lactobacillus acidophilus/fisiología , Microesferas , Extractos Vegetales/farmacología , Zingiber officinale/química , Animales , Colon/patología , Portadores de Fármacos/química , Ácido Glucurónico/química , Ácidos Hexurónicos/química , Masculino , Probióticos/farmacología , Ratas , Ratas WistarRESUMEN
BACKGROUND: Chemoprevention using natural agents has emerged as a new and promising strategy for reducing cancer burden. Sesamol, a water soluble lignin, is a potent antioxidant with potential anticancer activities. Its small size (molecular weight: 138.34g) coupled with easy permeability (log P: 1.29) results in its excessive systemic loss therefore, compromising local bioavailability. Furthermore, irritant nature of sesamol limits its application on skin per se. OBJECTIVE: Present study aims to evaluate chemopreventive efficacy of free and encapsulated (SLNs) sesamol, at gross and molecular level, in DMBA induced skin cancer animal model. METHODS: Evaluation is done in terms of tumor burden quantification, histological evaluation of skin, determination of oxidative stress, and quantification of apoptotic proteins, bcl-2 and bax, using both western blot analysis and immunofluorescence studies. RESULTS: Sesamol administration (both in free and encapsulated form) significantly decreased the tumor burden and lipid peroxidation level and increased anti-oxidant levels, thereby hampering the development and promotion of skin tumors. Further, downregulation of bcl-2 and stimulation of bax protein expression on treatment with both free and encapsulated sesamol was responsible for the induction of apoptosis in tumor cells. Encapsulating sesamol into SLNs not only reduced its irritant nature which limits its direct topical application but also improved its local targeting to skin. CONCLUSION: Both free and encapsulated sesamol demonstrated the inhibition of tumor progression by inducing skin cell apoptosis via bcl-2/bax mediated pathway.
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Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Benzodioxoles/farmacología , Fenoles/farmacología , Proteínas Proto-Oncogénicas c-bcl-2/biosíntesis , Neoplasias Cutáneas/tratamiento farmacológico , Proteína X Asociada a bcl-2/biosíntesis , Animales , Antineoplásicos/síntesis química , Antineoplásicos/química , Benzodioxoles/síntesis química , Benzodioxoles/química , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Masculino , Ratones , Ratones Endogámicos BALB C , Estructura Molecular , Fenoles/síntesis química , Fenoles/química , Neoplasias Cutáneas/metabolismo , Neoplasias Cutáneas/patología , Relación Estructura-ActividadRESUMEN
BACKGROUND: Multifaceted pathologies like cancers involve multiple targets. Failure of current treatment options modulating specific tumor target, evokes need for alternate approach of either combining several smart drugs or design a dirty drug that may simultaneously influence multiple targets to trigger a cascade of protective events complementing one another. METHODS: Present review tends to unravel the mechanism of anticancer action of ginger and also address issues, which may limit its realization as a biotherapeutic. RESULTS: Ginger exhibits a pleiotropy of antioxidant, anti-inflammatory, antiemetic, anticancer, and antimutagenic effects. In vivo and in vitro studies have established that phenolic components of ginger, particularly 6-gingerol and 6-shogaol induce apoptosis and autophagy and inhibit metastasis. The poor biological profile of ginger extract or its actives is due to its restricted biopharmaceutical properties. The gap in manifesting the curative/therapeutic effects of these agents can be plugged by assigning them with a suitable pharmaceutical couture. CONCLUSION: Hence, amalgamating the rational formulation design with observational folklore data available on herbal drugs/agents, complemented with scientific and precise in vitro and in vivo findings can bring out a class of safe, cheap, and effective curatives which can address multitarget diseases like cancers.
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Antineoplásicos Fitogénicos/farmacología , Neoplasias/tratamiento farmacológico , Zingiber officinale/química , Antineoplásicos Fitogénicos/química , Apoptosis/efectos de los fármacos , Humanos , Neoplasias/metabolismo , Neoplasias/patologíaRESUMEN
CONTEXT: Sesamol, a potential antioxidant with marked anticancer potential suffers from issues of extensive tissue distribution and local gastric irritation on oral administration. OBJECTIVE: To develop multiunit gastro-retentive floating beads (S-FBs) for localised and prolonged release of sesamol to treat gastric cancers. MATERIALS AND METHODS: S-FBs prepared using calcium carbonate, sodium alginate and hydroxypropylmethyl cellulose (HPMC) in different proportions, were characterised and evaluated in vivo in N-methyl-N-nitro-N-nitroguanidine-induced gastric cancer in rats. Single oral dose plasma pharmacokinetic study was also performed for free sesamol and S-FBs. RESULTS AND DISCUSSION: Restraining sesamol in floating beads, significantly lowered the release (diffusion controlled) rate, increased t50% (31 times) and reduced its in vivo clearance (>1.5 times). Preclinical evaluation showed S-FBs (10 mg/kg) to be significantly better than free sesamol and better/equivalent to methotrexate (2 mg/kg). CONCLUSION: Most of the natural phytochemical or antioxidants show pretreatment effectiveness. We, however, developed and established S-FBs for sustained curative effect.
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Benzodioxoles , Portadores de Fármacos , Neoplasias Experimentales/sangre , Neoplasias Experimentales/tratamiento farmacológico , Fenoles , Neoplasias Gástricas/sangre , Neoplasias Gástricas/tratamiento farmacológico , Animales , Benzodioxoles/química , Benzodioxoles/farmacocinética , Benzodioxoles/farmacología , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacología , Masculino , Neoplasias Experimentales/inducido químicamente , Fenoles/química , Fenoles/farmacocinética , Fenoles/farmacología , Ratas , Ratas Wistar , Neoplasias Gástricas/inducido químicamenteRESUMEN
Wound healing is a complex regenerative process of great importance in clinical medicine, controlled by temporal interactions between cells, extracellular matrix components and signalling molecules. Localised delivery of therapeutic active agents viz. antimicrobials, soothing minerals and/or vitamins and growth factors at the site of injury/trauma/wound are expected to be more effective and will always manifest milder toxic concerns than those observed upon systemic administration of these agents. Since ancient times, search is on for suitable materials which may restore or reproduce a favourable and a natural milieu required for skin regeneration, so as to prevent infections, and make the process fast and less painful. The journey started with the use of natural materials with a simple function of covering or dressing the wounds to more advanced materials of present times, which are designed for specific and extraordinary functions. Natural and modified or synthetic polymers; alone or in combination are commonly used as dressing (couture) materials for wound healing. This article offers a review of materials that have been used to design and develop wound dressings.
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Vendajes , Regeneración/fisiología , Cicatrización de Heridas/fisiología , Animales , Sistemas de Liberación de Medicamentos , Matriz Extracelular/metabolismo , Humanos , Polímeros/química , Piel/metabolismoRESUMEN
Abstract Role of reactive oxygen species (ROS) in skin carcinogenesis is well documented. Natural molecules, like sesamol, with marked antioxidant potential can be useful in combating skin cancers. In vitro antiproliferative (using MTT assay) and DNA fragmentation studies in HL 60 cell lines, confirmed the apoptotic nature of sesamol. However, it showed a significant flux across the mice skin upon topical application, such that its local availability in skin is limited. Former is attributed mainly to its properties like small size, low molecular weight (138.28), and a sufficient lipid and water solubility (log P 1.29; solubility 38.8 mg/ml). To achieve its maximum epicutaneous delivery, packaging it into a suitable carrier system is thus indicated. Sesamol-loaded solid lipid nanoparticles (S-SLN) were thus prepared with particle size of 127.9 nm (PI: 0.256) and entrapment efficiency of 88.21%. Topical application of S-SLN in a cream base indicated significant retention in the skin with minimal flux across skin as confirmed by the in-vivo skin retention and ex-vivo skin permeation studies. In vivo anticancer studies performed on TPA-induced and benzo(a)pyrene initiated tumour production (ROS mediated) in mouse epidermis showed the normalization (in histology studies) of skin cancers post their induction, upon treatment with S-SLN.
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Antineoplásicos Fitogénicos/uso terapéutico , Antioxidantes/uso terapéutico , Benzodioxoles/uso terapéutico , Portadores de Fármacos/química , Nanopartículas/química , Fenoles/uso terapéutico , Neoplasias Cutáneas/tratamiento farmacológico , Animales , Antineoplásicos Fitogénicos/administración & dosificación , Antineoplásicos Fitogénicos/química , Antioxidantes/administración & dosificación , Antioxidantes/química , Apoptosis/efectos de los fármacos , Benzodioxoles/administración & dosificación , Benzodioxoles/química , Composición de Medicamentos , Diseño de Fármacos , Estabilidad de Medicamentos , Células HL-60 , Humanos , Masculino , Ratones Endogámicos , Tamaño de la Partícula , Fenoles/administración & dosificación , Fenoles/química , Piel/efectos de los fármacos , Piel/metabolismo , Piel/patología , Absorción Cutánea , Neoplasias Cutáneas/metabolismo , Neoplasias Cutáneas/patología , Propiedades de SuperficieRESUMEN
The revolutionary and ubiquitous nature of nanotechnology has fetched it a considerable attention in the past few decades. Even though its enablement and application to various sectors including pharmaceutical drug development is increasing with the enormous government aided funding for nanotechnology-based products, however the parallel commercialization of these systems has not picked up a similar impetus. The technology however does address the unmet needs of pharmaceutical industry, including the reformulation of drugs to improve their solubility, bioavailability or toxicity profiles as observed from the wide array of high-quality research publications appearing in various scientific journals and magazines. Based on our decade-long experience in the field of nanotech-based drug delivery systems and extensive literature survey, we perceive that the major hiccups to the marketing of these nanotechnology products can be categorized as 1) inadequate regulatory framework; 2) lack of support and acceptance by the public, practicing physician, and industry; 3) developmental considerations like scalability, reproducibility, characterization, quality control, and suitable translation; 4) toxicological issues and safety profiles; 5) lack of available multidisciplinary platforms; and, 6) poor intellectual property protection. The present review dwells on these issues elaborating the trends followed by the industry, regulatory role of the USFDA and their implication, and the challenges set forth for a successful translation of these products from the lab and different clinical phases to the market.
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Industria Farmacéutica/economía , Industria Farmacéutica/tendencias , Nanotecnología/economía , Nanotecnología/tendencias , Sistemas de Liberación de Medicamentos , Industria Farmacéutica/legislación & jurisprudencia , Industria Farmacéutica/organización & administración , Financiación Gubernamental , Organización de la Financiación , Propiedad Intelectual , Nanotecnología/legislación & jurisprudencia , Nanotecnología/organización & administración , Preparaciones Farmacéuticas/administración & dosificación , Preparaciones Farmacéuticas/química , Seguridad , Transferencia de TecnologíaRESUMEN
Ginger extract (GE), a potential natural anticancer agent, has compromised therapeutic utilization due to poor bioavailability and physicochemical properties. Present study aimed at assigning GE with a pharmaceutical couture so as to improve its biopharmaceutical performance by monitoring its localized (though prolonged) delivery in the distal parts of gastrointestinal tract for the treatment of colon cancer. Alginate beads entrapping 85.9 ± 1.78% GE were subjected to Eudragit S100 coating. Latter is insoluble at acidic and near neutral (6.8) pH of stomach and upper part of small intestine and it led to 50% retardation (upto 12 h) in release of GE. However, it was solubilised at pH > 7.0 resulting in colon targeted system. Developed beads were free flowing, showed a particle size of 0.9 ± 0.006 mm and super class-II release controlled by swelling and polymer relaxation. Preclinical evaluation using 1,2-dimethylhydrazine-induced colon cancer, in male Wistar rats, in terms of histopathology, oxidative stress, mitochondrial complex activity, ß-glucuronidase and ammonia concentration determinations indicated GE loaded beads (50 mg/kg) to be significantly better (p < 0.05) than free GE. Highlight of the study was that GE loaded coated alginate beads were administered after the induction of colon cancer and significant recession of the cancers was observed after 4 weeks of treatment.
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Antineoplásicos Fitogénicos/uso terapéutico , Neoplasias del Colon/tratamiento farmacológico , Sistemas de Liberación de Medicamentos , Extractos Vegetales/uso terapéutico , Zingiber officinale/química , Alginatos/química , Animales , Antineoplásicos Fitogénicos/administración & dosificación , Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/farmacocinética , Antioxidantes/farmacología , Disponibilidad Biológica , Neoplasias del Colon/metabolismo , Neoplasias del Colon/patología , Portadores de Fármacos/química , Radicales Libres/química , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patología , Ácido Glucurónico/química , Ácidos Hexurónicos/química , Masculino , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/administración & dosificación , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/farmacocinética , Ratas , Ratas Wistar , SolubilidadRESUMEN
Lactobacillus acidophilus (LAB) loaded alginate floating beads (FBs) were developed with an intent to (i) preserve their viability during manufacture and upon exposure to adverse physiological conditions existing in the stomach, (ii) achieve an increased stay of the system in the stomach for improved pharmacodynamics and to provide for their effective establishment within the gastric mucosa. In vitro characterization of developed beads was performed in terms of entrapment efficiency, buoyancy, and surface as well as cross sectional morphology and viability studies of LAB in a gastric environment. The developed system was evaluated and was found to be significantly better in an experimental model of cold restraint stress (CRS) induced gastric ulcer model in terms of ulcer index, hemorrhagic streak length, histopathological and biochemical markers and their cross talk with reactive oxygen/nitrogen species. The present study emphasizes the advantages and future potential of probiotic loaded FBs in gastric disorders.