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Cancer is among the leading causes of mortality and morbidity in the world. Metallic nanoparticles, especially gold nanoparticles (AuNPs) have emerged to be attractive systems to circumvent the associated adverse effects. By the virtue of their unique properties of tunable size, shape, composition, optical properties, biocompatibility, minimal toxicity, multivalency, fluorescence-luminescence property and surface plasmon resonance; AuNPs have the potential to be used as drug delivery systems. It is vital to ensure that the drug reaches the target site of action for selective kill of cancer cells without harm to healthy cells. These AuNPs can be easily functionalized with a wide array of ligands like peptides, oligonucleotides, polymers, carbohydrates for active targeting to ensure site specific delivery and reduced systemic effects. AuNPs have been in-vestigated as carriers for gene delivery, drug delivery with or without photothermal therapy, in diagnosis based on radiation or spectroscopy. They have emerged as attractive theranostic approach in the overall management of cancer with superior benefit to risk features. In this review, we have discussed synthesis of different AuNPs (nanorods, spherical nanoparticles, and hollow AuNPs), their functionalization strategies and their applications in biomedical domain. Various research studies and clinical trials on application of AuNPs in diagnosis and therapeutics are highlighted.
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Sistemas de Liberação de Medicamentos , Ouro , Nanopartículas Metálicas , Neoplasias , Nanomedicina Teranóstica , Ouro/química , Ouro/administração & dosagem , Humanos , Nanopartículas Metálicas/química , Nanopartículas Metálicas/administração & dosagem , Neoplasias/terapia , Neoplasias/tratamento farmacológico , Nanomedicina Teranóstica/métodos , Animais , Sistemas de Liberação de Medicamentos/métodos , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Portadores de Fármacos/químicaRESUMO
PURPOSE: Drugs administered in the ocular region need to overcome ocular barriers without permanently damaging the ocular tissues. Moreover, ocular disorders of the posterior segment are more difficult to treat due to invasive procedures required to reach the posterior segment. Hence, to treat posterior disorders of the eye an attempt was made to develop nanofiber (NF) scaffolds for effective management of chronic posterior uveitis. Nanofibers (NFs) were formulated using the electrospinning technique. METHODS: NF scaffolds were formulated using the electrospinning technique. The effect of different concentrations of chitosan on NF production was studied by considering different ratios of chitosan (CS) and polyvinyl alcohol (PVA). Physicochemical characterization of NFs was performed to evaluate developed NFs. RESULTS: The optimized NF scaffold had a diameter of 129 ± 3 nm. NF scaffolds were found to have a tensile strength of 0.2882 ± 0.078 N/m2, thickness of 0.16 ± 0.05 mm, and drug entrapment of 95 ± 2.0%. The bioadhesive strength of the NF was found to be 257.3 ± 0.04 g/cm2 indicating high bioadhesion of NFs to the ocular tissues. The in-vitro, ex-vivo corneal and ex-vivo scleral drug release after 12 h was found to be 78.4 ± 1.0%, 65.33 ± 0.2% and 78.41 ± 1.0%, respectively. Ex-vivo whole eye model experiment indicated a concentration of about 40 ± 1.75% of drug permeated from corneal layer to the vitreous humor after 12 h. The Hen's egg test-chorioallantoic membrane study (HET-CAM) study and in-vitro cytotoxicity study on Statens Seruminstitut Rabbit Cornea (SIRC) cell lines indicated that the developed drug-loaded NF scaffolds were found to be non-toxic as compared to pure drug, thus suggesting cytocompatibility. CONCLUSION: Results of HET-CAM, sterility and ex-vivo studies indicate that the developed formulation is non-toxic, sterile, and effective for the ocular delivery of fluocinolone acetonide to the posterior segment of eye.
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Quitosana , Nanofibras , Animais , Feminino , Coelhos , Quitosana/química , Nanofibras/química , Fluocinolona Acetonida , Galinhas , Córnea/metabolismoRESUMO
BACKGROUND: Topical nanogel-based formulations have shown potential in the management of rheumatoid arthritis (RA). The aim of this research work was to explore the synergistic effect of Curcumin (CUR) and Cyclosporine (CYC) in combination via a topical route for the management of RA. METHODS: The CUR+CYC loaded nanoemulsion was developed using the spontaneous emulsification technique and was subsequently incorporated into Carbopol® Ultrez 30-NF gel. The effect of the developed formulation on levels of proinflammatory cytokines (IL-6, TNF-α) and anti-inflammatory cytokine (IL-10) was evaluated using lipopolysaccharide (LPS) induced RAW 264.7 cell culture model. The anti-arthritic activity was evaluated in a Complete Freund's Adjuvant (CFA) induced arthritic rat model. RESULTS: The optimized nanoemulgel (CUR + CYC NE gel) exhibited average globule size of 15.32 nm ±2.7 nm, poly-dispersity index of 0.181 ± 0.034 and zeta potential of -16.3 mV ± 0.9 mV. The cumulative drug release from ex-vivo diffusion studies on porcine ear skin was 99.189% ± 1.419% at the of 24 h and 99.177% ± 1.234% at the end of 18 h for CUR and CYC, respectively. The cell culture studies revealed that the formulation was able to significantly lower (p < .001) the levels of IL-6 and TNF-α, inhibited prostaglandin E2 (PGE2) while significantly elevating (p < .001) the levels of anti-inflammatory cytokine (IL-10). The gel was found to be non-irritating and showed the inhibition of paw edema and substantial reduction of arthritic symptoms in an arthritic rat model as compared to commercial and other conventional alternatives. CONCLUSION: This study highlights the potential of the developed nanoemulgel for the management of RA by enhancing the topical permeation of CUR and CYC.
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Artrite Reumatoide , Curcumina , Ratos , Animais , Suínos , Interleucina-10 , Ciclosporina , Fator de Necrose Tumoral alfa , Interleucina-6 , Artrite Reumatoide/tratamento farmacológico , Anti-Inflamatórios/uso terapêutico , CitocinasRESUMO
In recent years, natural ingredients have gained importance for therapeutic treatment due to their minimal toxicity. However, the delivery of these phytoconstituents poses a challenge to provide better efficacy. Current research reports the development of nanoemulgel (NEG) loaded with ginger oleoresin (GOR) and lipid guggul extract (LGE) for the management of rheumatoid arthritis (RA). The nanoemulsion (NE) was developed using the spontaneous emulsification technique by the pseudo-ternary method. The optimized nanoemulsion exhibited globule size of 16.08 ± 2.55 nm, PDI of 0.187 ± 0.06, and zeta potential of - 22.4 ± 0.31 mV. The cumulative release from in vitro diffusion studies at pH 7.4 was about 99.72 ± 3.47%, 57.98 ± 2.11%, and 86.42 ± 5.13% of 6-gingerol, E-guggulsterone, and Z-guggulsterone respectively at the end of 24 h. The ex vivo studies on porcine ear skin showed sustained release with 92.8 ± 3.21% for 6-gingerol, 55.61 ± 0.91% for E-guggulsterone, and 84.2 ± 4.22% for Z-guggulsterone released at the end of 24 h. The cell culture studies on RAW 264.7 cells indicated a robust inhibition of LPS-induced IL-6 and TNF-α production indicating its efficacy in the management of RA. The preclinical studies on male Wistar rats suggest that the developed NEG exhibited a comparable decrease in paw edema inflammation as compared to the marketed diclofenac sodium gel. These encouraging results demonstrate the potential of the developed nanoemulgel containing combination of GOR and LGE for the management of RA.
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Artrite Reumatoide , Pele , Ratos , Masculino , Animais , Suínos , Ratos Wistar , Pele/metabolismo , Absorção Cutânea , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/metabolismoRESUMO
Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome (HIV/ AIDS) and unplanned pregnancy affect female reproductive health globally. A single product providing a dual purpose of HIV prophylaxis and contraception may improve adherence to the therapy. Thus, we formulated a female-centric multipurpose prevention technology (MPT) comprising of nanoparticle loaded vaginal gel formulation acting as a contraceptive and microbicide. Eudragit® S100 nanoparticles of Atazanavir sulphate (ATZ; antiviral) and Fluoxetine hydrochloride (FLX; repurposed spermicide) were prepared for pH dependent drug release and loaded in carrageenan and HPMC K200M gel. The particle size of ATZ and FLX nanoparticles was 396.7 ± 20.64 nm and 226.5 ± 2.08 nm respectively. The in vitro release of the gel formulation in simulated seminal fluid (pH 7.6) showed 96.16% and 95.98% release of ATZ and FLX respectively at the end of 8 h. The in vitro anti-HIV and spermicidal activity of the formulation was above 80% for low drug concentrations. In vivo studies on murine model showed no signs of inflammation or vaginal epithelial injury. Curcumin based imaging confirmed the retention of the formulation in the reproductive tract of mice with minimal leakage. Nanoparticles in gel enabled non-invasive and localised delivery with minimal side effects and can be an effective prophylactic therapy.
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Infecções por HIV , Nanopartículas , Espermicidas , Gravidez , Feminino , Humanos , Animais , Camundongos , HIV , Gravidez não Planejada , Infecções por HIV/tratamento farmacológico , Infecções por HIV/prevenção & controle , Concentração de Íons de HidrogênioRESUMO
BACKGROUND: This study aims to formulate and characterize sorafenib-loaded resealed erythrocytes (SoRE) and investigate their anticancer activity in a rat model of hepatocellular carcinoma. METHODS: SoRE were prepared by hypotonic dialysis of red blood cells obtained from Wistar rats using a range of drug-containing dialysis mediums (2-10 mg/ml) and osmosis time (30-240 mins). Optimized SoRE (8 mg/mL and 240 mins) were characterized for size, morphology, stability, entrapment efficiency, in vitro release profiles, and in vivo efficacy evaluations. For efficacy studies, optimized SoRE were intravenously administered to Wistar rats having hepatocellular lesions induced by aflatoxin B and monitored for in vivo antineoplastic activity. RESULTS: The amount of sorafenib entrapped was directly proportional to the drug concentration in the dialysis medium and duration of osmosis; highest for 10 mg/mL and 240 minutes and lowest for 2 mg/mL and 30 minutes, respectively. Optimized SoRE were biconcave with a size of 112.7 nm and zeta potential of -11.95 ± 2.25 mV. Osmotic and turbulence fragility were comparable with native erythrocytes. CONCLUSION: Drug release follows the first-order pattern. In vivo investigations reveal better anticancer activity of SoRE formulation compared to sorafenib standard preparation. Resealed erythrocytes loaded with sorafenib displayed first-order in vitro release and promising anticancer activity in a rat model of hepatocellular carcinoma.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Ratos , Animais , Sorafenibe/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Ratos Wistar , Neoplasias Hepáticas/tratamento farmacológico , Diálise Renal , EritrócitosRESUMO
Attention Deficit Hyperactivity Disorder is a neurodevelopmental disorder, which is characterised by a distinct clinical pattern of inattention, hyperactivity as well as impulsivity, which in turn interferes with the day-to-day activities of the affected individual. Although conventional allopathic medications have been found to provide symptomatic relief, they are accompanied by a plethora of side effects that overshadow and outweigh the potential therapeutic benefits. Hence, various alternative approaches in the management of Attention Deficit Hyperactivity Disorder (ADHD) are actively being investigated. Over the past few decades, numerous studies have been initiated and have delved into potential alternative strategies in the treatment and management of ADHD. The primary focus of this article is to discuss the etiology, pathophysiology coupled with a financial background as well as alternative strategies in the treatment and management of ADHD. A review of the literature on the clinical trialson alternative treatment approaches for ADHD showed that, plants and dietary supplements have beneficial effects on ADHD management. But in-depth studies still need to be conducted because the trials reported till now have a smaller sample size and need to be scaled up to get a broader understanding and knowledge of the potential impact of alternative forms of natural treatment on the patient population with ADHD. Also, the manufacturer of the alternative formulations needs to develop effective protocols and processes for the safe, effective, and robust manufacturing of such natural remedies, which fall in line with the expectation of the FDA to gain regulatory clearance for its manufacturing and sale, which can lead to better therapeutic outcomes in patients.
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Transtorno do Deficit de Atenção com Hiperatividade , Humanos , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Suplementos Nutricionais , Comportamento ImpulsivoRESUMO
Alzheimer's disease, a progressive neurodegenerative condition, is characterized by a gradual decline in cognitive functions. Current treatment approaches primarily involve the administration of medications through oral, parenteral, and transdermal routes, aiming to improve cognitive function and alleviate symptoms. However, these treatments face limitations, such as low bioavailability and inadequate permeation. Alternative invasive methods, while explored, often entail discomfort and require specialized assistance. Therefore, the development of a non-invasive and efficient delivery system is crucial. Intranasal delivery has emerged as a potential solution, although it is constrained by the unique conditions of the nasal cavity. An innovative approach involves the use of nano-carriers based on nanotechnology for intranasal delivery. This strategy has the potential to overcome current limitations by providing enhanced bioavailability, improved permeation, effective traversal of the blood-brain barrier, extended retention within the body, and precise targeting of the brain. The comprehensive review focuses on the advancements in designing various types of nano-carriers, including polymeric nanoparticles, metal nanoparticles, lipid nanoparticles, liposomes, nanoemulsions, Quantum dots, and dendrimers. These nano-carriers are specifically tailored for the intranasal delivery of therapeutic agents aimed at combatting Alzheimer's disease. In summary, the development and utilization of intranasal delivery systems based on nanotechnology show significant potential in surmounting the constraints of current Alzheimer's disease treatment strategies. Nevertheless, it is essential to acknowledge regulatory as well as toxicity concerns associated with this route; meticulous consideration is required when engineering a carrier. This comprehensive review underscores the potential to revolutionize Alzheimer's disease management and highlights the importance of addressing regulatory considerations for safe and effective implementations. Embracing this strategy could lead to substantial advancements in the field of Alzheimer's disease treatment.
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Nanofibers due to their unique properties such as high surface-to-volume ratio, porous structure, mechanical strength, flexibility and their resemblance to the extracellular matrix, have been researched extensively in the field of ocular drug delivery and tissue engineering. Further, different modifications considering the formulation and process parameters have been carried out to alter the drug release profile and its interaction with the surrounding biological environment. Electrospinning is the most commonly used technique for preparing nanofibers with industrial scalability. Advanced techniques such as co-axial electrospinning and combined system such as embedding nanoparticles in nanofiber provide an alternative approach to enhance the performance of the scaffold. Electrospun nanofibers offers a matrix like structure for cell regeneration. Nanofibers have been used for ocular delivery of various drugs like antibiotics, anti-inflammatory and various proteins. In addition, lens-coated medical devices provide new insights into the clinical use of nanofibers. Through fabricating the nanofibers researchers have overcome the issues of low bioavailability and compatibility with ocular tissue. Therefore, nanofibers have great potential in ocular drug delivery and tissue engineering and have the capacity to revolutionize these therapeutic areas in the field of ophthalmology. This review is mainly focused on the recent advances in the preparation of nanofibers and their applications in ocular drug delivery and tissue engineering. The authors have attempted to emphasize the processing challenges and future perspectives along with an overview of the safety and toxicity aspects of nanofibers.
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Nanofibras , Antibacterianos , Sistemas de Liberação de Medicamentos , Nanofibras/química , Polímeros/química , Engenharia Tecidual/métodosRESUMO
Hollow gold nanoparticles (HAuNPs) are gold nanostructures with hollow interior. These particles have attracted a lot of interest due their excellent physicochemical and optical properties and their potential applications in diagnostics, sensing, imaging and assisting in tumor tracing and evaluating the effect of chemotherapy on tumor size, drug delivery and photothermal therapy. Sacrificial galvanic replacement using cobalt core is the most commonly used method for synthesis of HAuNPs. However, lack of reproducibility in synthesizing particles with desired surface plasmon resonance (SPR) is one of the major concerns for clinical application of these particles. In this work, we have identified and categorized various factors that could affect uniformity of cobalt core and subsequent formation of gold shell. Using slight modifications in the method, we have been able to synthesize HAuNPs with SPR in near infrared region at 808 nm with size of particles around 50-80 nm. HAuNPs can be further functionalized with suitable ligands like glutathione, polyethylene glycol, nucleic acids, sugars, fatty acids, proteins and peptides to promote enhanced permeability and retention in cancer cells and thus can serve as potential candidates in treatment of cancer.
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Nanopartículas Metálicas , Neoplasias , Ácidos Nucleicos , Cobalto , Ácidos Graxos , Glutationa , Ouro/química , Humanos , Ligantes , Nanopartículas Metálicas/química , Neoplasias/terapia , Polietilenoglicóis , Reprodutibilidade dos Testes , AçúcaresRESUMO
Wound management is an unmet therapeutic challenge and a global healthcare burden. Current treatment strategies provide limited efficiency in wound management, thus undergoing constant evolution in the treatment approaches. As wound healing is a complex physiological process involving precise synchronization of various phases like hemostasis, inflammation and remodelling, which necessitates innovative treatment strategies. Nanotechnology platforms like polymeric nanofibers (NFs) offer a promising solution for wound management. NFs contain a porous mesh-like structure that mimics the natural extracellular matrix and promote the cell adhesion and proliferation in the wound bed, thus displaying a great potential as a wound healing scaffold. Electrospinning is a simple, versatile and scalable technique for producing highly porous and tuneable NFs with a high surface area. Electrospun NFs are presenting extensive application in wound management, especially for burns and diabetic foot ulcers. This review briefly discusses the wound physiology and conventional treatment strategies. It also provides an overview of the electrospinning process and its principle, highlighting the application of electrospun polymeric NFs in wound management. The authors have made an attempt to emphasizes on the clinical challenges and future perspectives along with regulatory aspects of NFs as a wound dressing.
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Nanofibras , Bandagens , Humanos , Nanofibras/química , Nanotecnologia/métodos , Polímeros , CicatrizaçãoRESUMO
Skin aging is the progressive biological process generally characterized by the appearance of wrinkles, age spots, sagging of skin, and dryness. Since skin is an essential part of physical appearance, this has led to increased concerns about skincare. Anti-aging products help in improving the quality and health of the skin by nourishing it. However, due to large particle size they are less efficacious. Nanotechnological approaches for topical anti-aging products have a significant effect on the product performance. Lipidic, polymeric, and metallic nanoparticles have shown potential advantages like enhanced stability and efficacy due to their smaller size. The excipients used in these nanoformulations play an important role in improving the efficacy and shelf-life of the product. The optimal selection of excipients plays a major role in the nanoformulation approach for their enhanced efficacy and stability. For the past three decades the ingredients of natural origin for cosmetic formulations have been widely recognized for being safe and less toxic. The objective of this article is to review the nanoformulations used in anti-aging along with the potential excipients used, currently marketed formulations, and patents filed for cosmetic use. Recent updates related to regulatory aspects of the nanocosmetics have also been highlighted.
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Cosméticos , Envelhecimento da Pele , Envelhecimento , Composição de Medicamentos , Excipientes , HumanosRESUMO
Upconverting luminescent nanoparticles (UCNPs) are "new generation fluorophores" with an evolving landscape of applications in diverse industries, especially life sciences and healthcare. The anti-Stokes emission accompanied by long luminescence lifetimes, multiple absorptions, emission bands, and good photostability, enables background-free and multiplexed detection in deep tissues for enhanced imaging contrast. Their properties such as high color purity, high resistance to photobleaching, less photodamage to biological samples, attractive physical and chemical stability, and low toxicity are affected by the chemical composition; nanoparticle crystal structure, size, shape and the route; reagents; and procedure used in their synthesis. A wide range of hosts and lanthanide ion (Ln3+) types have been used to control the luminescent properties of nanosystems. By modification of these properties, the performance of UCNPs can be designed for anticipated end-use applications such as photodynamic therapy (PDT), high-resolution displays, bioimaging, biosensors, and drug delivery. The application landscape of inorganic nanomaterials in biological environments can be expanded by bridging the gap between nanoparticles and biomolecules via surface modifications and appropriate functionalization. This review highlights the synthesis, surface modification, and biomedical applications of UCNPs, such as bioimaging and drug delivery, and presents the scope and future perspective on Ln-doped UCNPs in biomedical applications.
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Microbial pathogens are the most prevalent cause of chronic infections and fatalities around the world. Antimicrobial agents including antibiotics have been frequently utilized in the treatment of infections due to their exceptional outcomes. However, their widespread use has resulted in the emergence of multidrug-resistant strains of bacteria, fungi, viruses, and parasites. Furthermore, due to inherent resistance to antimicrobial drugs and the host defence system, the advent of new infectious diseases, chronic infections, and the occurrence of biofilms pose a tougher challenge to the current treatment line. Essential oils (EOs) and their biologically and structurally diverse constituents provide a distinctive, inexhaustible, and novel source of antibacterial, antiviral, antifungal, and antiparasitic agents. However, due to their volatile nature, chemical susceptibility, and poor solubility, their development as antimicrobials is limited. Nanoparticles composed of biodegradable polymeric and inorganic materials have been studied extensively to overcome these limitations. Nanoparticles are being investigated as nanocarriers for antimicrobial delivery, antimicrobial coatings for food products, implantable devices, and medicinal materials in dressings and packaging materials due to their intrinsic capacity to overcome microbial resistance. Essential oil-loaded nanoparticles may offer the potential benefits of synergism in antimicrobial activity, high loading capacity, increased solubility, decreased volatility, chemical stability, and enhancement of the bioavailability and shelf life of EOs and their constituents. This review focuses on the potentiation of the antimicrobial activity of essential oils and their constituents in nanoparticulate delivery systems for a wide range of applications, such as food preservation, packaging, and alternative treatments for infectious diseases.
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The skin is the largest organ of the integumentary system with a multifunctional purpose to protect the body from heat and microbes, regulate body temperature, and act as a sensory organ. A topical dosage form applied on the skin will have to cross the stratum corneum, which would then allow the dosage form to traverse the subsequent layers of the skin. The drug with poor solubility and short half-life would serve as an ideal candidate for its delivery via the transdermal route. This review reports the role of natural oils in enhancing the permeation of drugs through skin as they possess different features like natural origin, favorable penetration enhancement, and partitioning action in the skin. Chemical penetration enhancers have been used widely but are associated with toxicities. Thus, more research should be channelized in the area of extraction of oils from natural sources, along with their active constituents, which can serve as therapeutic alternatives to various disorders and diseases. Natural oils are obtained from leaves, fruits, flowers, seeds, bark, and roots, which have a therapeutic potential as well as penetration enhancing activity. The demerits of oral drug delivery include degradation of drugs in the gastrointestinal tract, addition of taste masking, and coating of tablets, which can be overcome by delivering the drug via the transdermal route. Natural oil contains lipids, flavonoids, and terpenes, which play a significant role in anti-inflammatory and penetration enhancing activity.
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Óleos , Absorção Cutânea , Administração Cutânea , Sistemas de Liberação de Medicamentos , Humanos , Preparações FarmacêuticasRESUMO
One of the major impediments to drug development is low aqueous solubility and thus poor bioavailability, which leads to insufficient clinical utility. Around 70-80% of drugs in the discovery pipeline are suffering from poor aqueous solubility and poor bioavailability, which is a major challenge when one has to develop an ocular drug delivery system. The outer lipid layer, pre-corneal, dynamic, and static ocular barriers limit drug availability to the targeted ocular tissues. Biopharmaceutical Classification System (BCS) class II drugs with adequate permeability and limited or no aqueous solubility have been extensively studied for various polymer-based solubility enhancement approaches. The hydrophilic nature of cellulosic polymers and their tunable properties make them the polymers of choice in various solubility-enhancement techniques. This review focuses on various cellulose derivatives, specifically, their role, current status and novel modified cellulosic polymers for enhancing the bioavailability of BCS class II drugs in ocular drug delivery systems.
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INTRODUCTION: Chronic wounds are a substantial burden on the healthcare system. Their treatment requires advanced dressings, which can provide a moist wound environment, prevent bacterial infiltration, and act as a drug carrier. Cellulose is biocompatible, biodegradable, and can be functionalized according to specific requirements, which makes it a highly versatile biomaterial. Antimicrobial cellulose dressings are proving to be highly effective against infected wounds. AREAS COVERED: This review briefly addresses the mechanism of wound healing and its pathophysiology. It also discusses wound infections, biofilm formation, and progressive emergence of drug-resistant bacteria in chronic wounds and the treatment strategies for such types of infected wounds. It also summarizes the general properties, method of production, and types of cellulose wound dressings. It explores recent studies and advancements regarding the use of cellulose and its derivatives in wound management. EXPERT OPINION: Cellulose and its various functionalized derivatives represent a promising choice of wound dressing material. Cellulose-based dressings loaded with antimicrobials are very useful in controlling infection in a chronic wound. Recent studies showing its efficacy against drug-resistant bacteria make it a favorable choice for chronic wound infections. Further research and large-scale clinical trials are required for better clinical evidence of its efficiency.
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Materiais Biocompatíveis , Infecção dos Ferimentos , Bandagens , Celulose , Humanos , Cicatrização , Infecção dos Ferimentos/tratamento farmacológicoRESUMO
In phenylketonuria (PKU) patients, a genetic defect in the enzyme phenylalanine hydroxylase (PAH) leads to elevated systemic phenylalanine (Phe), which can result in severe neurological impairment. As a treatment for PKU, Escherichia coli Nissle (EcN) strain SYNB1618 was developed under Synlogic's Synthetic Biotic™ platform to degrade Phe from within the gastrointestinal (GI) tract. This clinical-stage engineered strain expresses the Phe-metabolizing enzyme phenylalanine ammonia lyase (PAL), catalyzing the deamination of Phe to the non-toxic product trans-cinnamate (TCA). In the present work, we generate a more potent EcN-based PKU strain through optimization of whole cell PAL activity, using biosensor-based high-throughput screening of mutant PAL libraries. A lead enzyme candidate from this screen is used in the construction of SYNB1934, a chromosomally integrated strain containing the additional Phe-metabolizing and biosafety features found in SYNB1618. Head-to-head, SYNB1934 demonstrates an approximate two-fold increase in in vivo PAL activity compared to SYNB1618.
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Terapia Biológica , Proteínas de Escherichia coli/genética , Escherichia coli/enzimologia , Fenilalanina Amônia-Liase/genética , Fenilalanina/metabolismo , Fenilcetonúrias/metabolismo , Fenilcetonúrias/terapia , Técnicas Biossensoriais , Cinamatos , Escherichia coli/genética , Escherichia coli/metabolismo , Proteínas de Escherichia coli/metabolismo , Humanos , Fenilalanina Amônia-Liase/metabolismo , Engenharia de ProteínasRESUMO
Several ocular drug delivery (ODD) systems, like hydrogels, microparticles, nano-emulsions, micro-emulsions, and liposomes have been researched, which can govern the drug release and sustain therapeutic levels for a delayed period in the eye. While new drugs targeting methods to the eye are possible by various nanoparticles. Presently in the market, there are fewer choices and need for novel nano-ocular delivery systems as well as therapies for prolonged delivery to the anterior and posterior eye segments. The primary objective of this article is to summarize current discoveries and proven activities of different nano- and microsystems in ODD. This article also depicts some regulatory updates along with the patents granted to the inventor for their work on ODD. Overall, a thought of how the different forthcoming of nanotechnologies like nanoparticles and nanomedicine can be used to investigate the frontiers of ODD and treatment can be withdrawn by this article.