Design, optimization, and evaluation of methotrexate loaded and albumin coated polymeric nanoparticles.

Methotrexate is a potent anticancer drug whose strong efflux is facilitated by the brain's efflux transporter. As an efflux transporter blocker, albumin increased the drug's concentration in the brain. Methotrexate-loaded nanoparticles were produced by evaporating the emulsification fluid. Improvements and analyses were made to the following aspects of the generated nanoparticles: size, polydispersity, zeta potential, entrapment efficiency, percentage yield, scanning electron microscopy, in vitro drug release studies, and sterilization. The particle size was determined to be in the nano range, and homogeneity of particle size was suggested by a low polydispersity index result. Particle diameters of 168 nm were observed in the F5 preparation, and zeta potential values of -1.5 mV suggested that the preparation produced adequate repulsive interactions between the nanoparticles. Albumin and dopamine HCl were employed to coat the methotrexate-loaded nanoparticles to guarantee that the brain received an adequate amount of them. The homogeneity of albumin coated nanoparticles was demonstrated by the low% PDI values of 0.129 and 0.122 for albumin coated nanoparticles (MNPs-Alb) and polymerized dopamine HCl and albumin coated nanoparticles (MNPs-PMD-Alb), respectively. After 48 h of incubation, the cell viability measured at the same drug concentration (5 mg) decreased for the F5, albumin coated nanoparticles, polymerized dopamine HCl coated nanoparticles, and polymerized dopamine HCl and albumin coated nanoparticles, respectively. Our primary findings demonstrate that the albumin nanoparticles containing methotrexate are designed to deliver the drug gradually. With minimal cytotoxicity, the intended preparation might give the brain an appropriate dosage of methotrexate.

Circulating Metabolite Biomarkers of Glycemic Control in Youth-Onset Type 2 Diabetes.

OBJECTIVE: We aimed to identify metabolites associated with loss of glycemic control in youth-onset type 2 diabetes. RESEARCH DESIGN AND METHODS: We measured 480 metabolites in fasting plasma samples from the TODAY (Treatment Options for Type 2 Diabetes in Adolescents and Youth) study. Participants (N = 393; age 10-17 years) were randomly assigned to metformin, metformin plus rosiglitazone, or metformin plus lifestyle intervention. Additional metabolomic measurements after 36 months were obtained in 304 participants. Cox models were used to assess baseline metabolites, interaction of metabolites and treatment group, and change in metabolites (0-36 months), with loss of glycemic control adjusted for age, sex, race, treatment group, and BMI. Metabolite prediction models of glycemic failure were generated using elastic net regression and compared with clinical risk factors. RESULTS: Loss of glycemic control (HbA1c ≥8% or insulin therapy) occurred in 179 of 393 participants (mean 12.4 months). Baseline levels of 33 metabolites were associated with loss of glycemic control (q < 0.05). Associations of hexose and xanthurenic acid with treatment failure differed by treatment randomization; youths with higher baseline levels of these two compounds had a lower risk of treatment failure with metformin alone. For three metabolites, changes from 0 to 36 months were associated with loss of glycemic control (q < 0.05). Changes in d-gluconic acid and 1,5-AG/1-deoxyglucose, but not baseline levels of measured metabolites, predicted treatment failure better than changes in HbA1c or measures of ß-cell function. CONCLUSIONS: Metabolomics provides insight into circulating small molecules associated with loss of glycemic control and may highlight metabolic pathways contributing to treatment failure in youth-onset diabetes.

Nano-Formulation Approaches to Enhance Transdermal Drug Delivery-An Updated Review of Nanovesicular Carrier "Transethosomes".

Transdermal drug delivery is an attractive and patient-friendly route for administering therapeutic agents. However, the skin's natural barrier, the stratum corneum, restricts the passage of many drugs, limiting their effectiveness. To overcome this challenge, researchers have developed various nanocarriers to enhance drug penetration through the skin. Transethosomes, a novel and promising drug delivery system, have emerged as an innovative solution for improving transdermal drug delivery. Transethosomes are a hybrid of two established nanocarriers: ethosomes and transfersomes. Ethosomes are lipid-based vesicles that can accommodate lipophilic and hydrophilic drugs, while transfersomes are deformable lipid vesicles designed to enhance skin penetration. Transethosomes combine the advantages of both systems, making them ideal candidates for efficient transdermal drug delivery. They are composed of phospholipids, ethanol, and water and exhibit high flexibility, enabling them to squeeze through the tight junctions of the stratum corneum. This abstract reviews the key characteristics of transethosomes, including their composition, preparation methods, mechanisms of action, characterization parameters, and prospects. Moreover, the recent advancements and applications of transethosomes in delivering various therapeutic agents, such as analgesics, anti-inflammatories, hormones, and skincare products, are explored. The enhanced skin penetration capabilities of transethosomes can potentially reduce systemic side effects and improve patient compliance, making them a valuable tool in the field of transdermal drug delivery. In conclusion, transethosomes represent a promising platform for overcoming the challenges of transdermal drug delivery. Their unique properties enable efficient drug permeation through the skin, offering a more controlled and effective means of administering a wide range of pharmaceutical and cosmetic products. This abstract highlights the potential of transethosomes as a valuable addition to the field of transdermal drug delivery and paves the way for further research and development in this area.

Recent advancements in nanomaterial-mediated ferroptosis-induced cancer therapy: Importance of molecular dynamics and novel strategies.

Ferroptosis is a novel type of controlled cell death resulting from an imbalance between oxidative harm and protective mechanisms, demonstrating significant potential in combating cancer. It differs from other forms of cell death, such as apoptosis and necrosis. Molecular therapeutics have hard time playing the long-acting role of ferroptosis induction due to their limited water solubility, low cell targeting capacity, and quick metabolism in vivo. To this end, small molecule inducers based on biological factors have long been used as strategy to induce cell death. Research into ferroptosis and advancements in nanotechnology have led to the discovery that nanomaterials are superior to biological medications in triggering ferroptosis. Nanomaterials derived from iron can enhance ferroptosis induction by directly releasing large quantities of iron and increasing cell ROS levels. Moreover, utilizing nanomaterials to promote programmed cell death minimizes the probability of unfavorable effects induced by mutations in cancer-associated genes such as RAS and TP53. Taken together, this review summarizes the molecular mechanisms involved in ferroptosis along with the classification of ferroptosis induction. It also emphasized the importance of cell organelles in the control of ferroptosis in cancer therapy. The nanomaterials that trigger ferroptosis are categorized and explained. Iron-based and noniron-based nanomaterials with their characterization at the molecular and cellular levels have been explored, which will be useful for inducing ferroptosis that leads to reduced tumor growth. Within this framework, we offer a synopsis, which traverses the well-established mechanism of ferroptosis and offers practical suggestions for the design and therapeutic use of nanomaterials.

Lac-Phe mediates the effects of metformin on food intake and body weight.

Metformin is a widely prescribed anti-diabetic medicine that also reduces body weight. There is ongoing debate about the mechanisms that mediate metformin's effects on energy balance. Here, we show that metformin is a powerful pharmacological inducer of the anorexigenic metabolite N-lactoyl-phenylalanine (Lac-Phe) in cells, in mice and two independent human cohorts. Metformin drives Lac-Phe biosynthesis through the inhibition of complex I, increased glycolytic flux and intracellular lactate mass action. Intestinal epithelial CNDP2+ cells, not macrophages, are the principal in vivo source of basal and metformin-inducible Lac-Phe. Genetic ablation of Lac-Phe biosynthesis in male mice renders animals resistant to the effects of metformin on food intake and body weight. Lastly, mediation analyses support a role for Lac-Phe as a downstream effector of metformin's effects on body mass index in participants of a large population-based observational cohort, the Multi-Ethnic Study of Atherosclerosis. Together, these data establish Lac-Phe as a critical mediator of the body weight-lowering effects of metformin.

Lac-Phe mediates the anti-obesity effect of metformin.

Metformin is a widely prescribed anti-diabetic medicine that also reduces body weight. The mechanisms that mediate metformin's effects on energy balance remain incompletely defined. Here we show that metformin is a powerful pharmacological inducer of the anorexigenic metabolite Lac-Phe in mice as well as in two independent human cohorts. In cell culture, metformin drives Lac-Phe biosynthesis via inhibition of complex I, increased glycolytic flux, and intracellular lactate mass action. Other biguanides and structurally distinct inhibitors of oxidative phosphorylation also increase Lac-Phe levels in vitro. Genetic ablation of CNDP2, the principal biosynthetic enzyme for Lac-Phe, in mice renders animals resistant to metformin's anorexigenic and anti-obesity effects. Mediation analyses also support a role for Lac-Phe in metformin's effect on body mass index in humans. These data establish the CNDP2/Lac-Phe pathway as a critical mediator of the effects of metformin on energy balance.

Therapeutic and Phytochemical Properties of Thymoquinone Derived from Nigella Sativa.

BACKGROUND: Nigella sativa (N. sativa), commonly known as black seed or black cumin, belongs to the family Ranunculaceae. It contains several phytoconstituents, thymoquinone (TQ), thymol, thymohydroquinone, carvacrol, and dithymoquinone. TQ is the main phytoconstituent present in N. sativa that is used as an herbal compound, and it is widely used as an antihypertensive, liver tonic, diuretic, digestive, anti-diarrheal, appetite stimulant, analgesic, and antibacterial agent, and in skin disorders. OBJECTIVE: The study focused on collecting data on the therapeutic or pharmacological activities of TQ present in N. sativa seed. METHODS: Antidiabetic, anticancer, immunomodulator, analgesic, antimicrobial, antiinflammatory, hepato-protective, renal protective, and antioxidant properties of TQ have been studied by various scientists. CONCLUSION: TQ seems to have a variety of consequences on how infected cells behave at the cellular level.

Expanded therapeutic applications of Holarrhena antidysenterica: A review.

BACKGROUND: The use of medicinal plants as a rich resource of therapeutic agents in the treatment and prevention of diseases & ailments has been recognized for millennia and is highly regarded worldwide. Holarrhena antidysenterica (H. antidysenterica), also called kurchi, or kutaj, has been utilized since the dawn of time, Apocynaceae member, also known as H. pubescens, is praised for the medicinal uses of its stem bark, leaves, and seeds in Ayurveda. OBJECTIVE: The study concentrated on aggregate information regarding H. antidysenterica's therapeutic effects. The purpose of this study was to determine the antidiabetic activity of an extract from H. antidysenterica seeds in diabetic rats induced by streptozotocin. METHODS: Regardless of its broad variety of biological and possible therapeutic uses, there has been increasing concern regarding the use of H. antidysenterica. RESULT: Various phytochemicals have been extracted from H. antidysenterica in recent years and have demonstrated typical pharmacological properties, including antibacterial, anti-diarrhoeal, anti-diabetic, anti-oxidant, anti-urolithic, and anti-inflammatory activity.. CONCLUSION: This review paper investigated the in-depth description and pharmacological properties of the plant, which produced significant findings on the chemical components present and also verified the traditionally claimed properties associated with the plant.

Using machine learning for healthcare treatment planning.

We present a methodology for using machine learning for planning treatments. As a case study, we apply the proposed methodology to Breast Cancer. Most of the application of Machine Learning to breast cancer has been on diagnosis and early detection. By contrast, our paper focuses on applying Machine Learning to suggest treatment plans for patients with different disease severity. While the need for surgery and even its type is often obvious to a patient, the need for chemotherapy and radiation therapy is not as obvious to the patient. With this in mind, the following treatment plans were considered in this study: chemotherapy, radiation, chemotherapy with radiation, and none of these options (only surgery). We use real data from more than 10,000 patients over 6 years that includes detailed cancer information, treatment plans, and survival statistics. Using this data set, we construct Machine Learning classifiers to suggest treatment plans. Our emphasis in this effort is not only on suggesting the treatment plan but on explaining and defending a particular treatment choice to the patient.

Pharmaceutical Considerations of Translabial Formulations for Treatment of Parkinson's Disease: A Concept of Drug Delivery for Unconscious Patients.

PURPOSE: The goal of the present research was to isolate a biopolymer from Phaseolus vulgaris (P. vulgaris) and Zea mays (Z. mays) plants and used it to construct Resveratrol (RES)-loaded translabial films. METHODS: Biopolymers were extracted from P. vulgaris and Z. mays seeds using a simple process. Separated biopolymers, sodium carboxymethylcellulose (SCMC) and tragacanth were subjected to formulation development by incorporating RES-loaded translabial films. The Fourier-transform infrared spectroscopy (FTIR), physical appearance, weight, thickness, folding endurance, swelling index, surface pH, percent moisture absorption, percent moisture loss, vapor transfer rate, and content uniformity of the translabial films were examined. The mucoadhesive, ex-vivo permeation, in vivo and stability studies, were performed. RESULTS: The results showed that RES-loaded translabial films produced from P. vulgaris and Z. mays biopolymers exhibited exceptional mucoadhesive, stability, and permeation properties. Results revealed that the best formulations were prepared from a combination of biopolymer (P. vulgaris C or Z. mays C) with tragacanth. Formulations with tragacanth revealed good swelling and thus permeation profiles. In vivo release of TL 11 was found to be 24.05 ng/ml in 10 hours and it was stable enough at 45°C. CONCLUSION: This research suggested that RES-loaded translabial formulations can be potentially used for the treatment of Parkinson's disease with good patient compliance to geriatric and unconscious patients.

Preventive and Therapeutic Aspects of Migraine for Patient Care: An Insight.

BACKGROUND: Migraine is a common neurological condition marked by frequent mild to extreme headaches that last 4 to 72 hours. A migraine headache may cause a pulsing or concentrated throbbing pain in one part of the brain. Nausea, vomiting, excessive sensitivity to light and sound, smell, feeling sick, vomiting, painful headache, and blurred vision are all symptoms of migraine disorder. Females are more affected by migraines in comparison to males. OBJECTIVE: The present review article summarizes preventive and therapeutic measures, including allopathic and herbal remedies for the treatment of migraine. RESULTS: This review highlights the current aspects of migraine pathophysiology and covers an understanding of the complex workings of the migraine state. Therapeutic agents that could provide an effective treatment have also been discussed. CONCLUSION: It can be concluded that different migraines could be treated based on their type and severity.

An Exploration of Herbal Extracts Loaded Phyto-phospholipid Complexes (Phytosomes) Against Polycystic Ovarian Syndrome: Formulation Considerations.

BACKGROUND: Herbal preparations with low oral bioavailability have a fast first-pass metabolism in the gut and liver. To offset these effects, a method to improve absorption and, as a result, bioavailability must be devised. OBJECTIVE: The goal of this study was to design, develop, and assess the in vivo toxicity of polyherbal phytosomes for ovarian cyst therapy. METHODS: Using antisolvent and rotational evaporation procedures, phytosomes containing phosphatidylcholine and a combination of herbal extracts (Saraca asoca, Bauhinia variegata, and Commiphora mukul) were synthesized. For a blend of Saraca asoca, Bauhinia variegata, and Commiphora mukul, Fourier-transform infrared spectroscopy (FTIR), preformulation investigations, qualitative phytochemical screening, and UV spectrophotometric tests were conducted. Scanning electron microscopy (SEM), zeta potential, ex vivo release, and in vivo toxicological investigations were used to examine phytosomes. RESULTS: FTIR studies suggested no changes in descriptive peaks in raw and extracted herbs, although the intensity of peaks was slightly reduced. Zeta potential values between -20.4 mV to - 29.6 mV suggested stable phytosomes with an accepted particle size range. Percentage yield and entrapment efficiency were directly correlated to the amount of phospholipid used. Ex vivo studies suggested that the phytosomes with low content of phospholipids showed good permeation profiles. There was no difference in clinical indications between the extract-loaded phytosomes group and the free extract group in in vivo toxicological or histopathological examinations. CONCLUSION: The findings of current research work suggested that the optimized phytosomes based drug delivery containing herbal extracts as bioenhancers has the potential to improve the bioavailability of hydrophobic extracts.

Nrf2 Mediated Heme Oxygenase-1 Activation Contributes to Diabetic Wound Healing - an Overview.

Diabetic wound healing is a complicated procedure because hyperglycemia changes the various stages of wound healing. In type 2 diabetes mellitus (T2DM), oxidative stress is proven to be a critical factor in causing non-healing wounds and aggravating the inflammatory phase, resulting in the amputation of lower limbs in T2DM patients. This makes scientists figure out how to control oxidative stress and chronic inflammation at the molecular level. Nuclear factor erythroid 2- related factor 2 (Nrf2) releases antioxidant proteins to suppress reactive oxygen species (ROS) activation and inflammation. The current review discusses the role of Nrf2 in improving diabetic wound healing by reducing the production of ROS and thus reducing oxidative stress, as well as inhibiting nuclear factor kappa B (NF-kB) dissociation and nuclear translocation, which prevents the release of inflammatory mediators and increases antioxidant protein levels, thereby improving diabetic wound healing. As a result, the researcher will be able to find a more effective diabetic wound healing therapy.

Biochanin-A: A Bioactive Natural Product with Versatile Therapeutic Perspectives.

BACKGROUND: Biochanin-A (5,7 dihydroxy 4 methoxy isoflavone) is a phytochemical phytoestrogen that is highly effective against various diseases. Biochanin-A is a nutritional and dietary isoflavonoid naturally present in red clover, chickpea, soybeans and other herbs. Biochanin- A possesses numerous biological activities. OBJECTIVE: The study focused on collective data of therapeutic activities of Biochanin-A. METHODS: According to the literature, biochanin-A revealed a range of activities starting from chemoprevention, by hindering cell growth, activation of tumor cell death, hampering metastasis, angiogenic action, cell cycle regulation, neuroprotection, by controlling microglial activation, balancing antioxidants, elevating the neurochemicals, suppressing BACE-1, NADPH oxidase hindrance to inflammation, by mitigating the MAPK and NF- κB, discharge of inflammatory markers, upregulating the PPAR-γ, improving the function of heme oxygenase-1, erythroid 2 nuclear factors, detoxifying the oxygen radicals and stimulating the superoxide dismutase action, and controlling its production of transcription factors. Against pathogens, biochanin-A acts by dephosphorylating tyrosine kinase proteins, obstructing gram-negative bacteria, suppressing the development of cytokines from viruses, and improving the action of a neuraminidase cleavage of caspase-3, and acts as an efflux pump inhibitor. In metabolic disorders, biochanin-A acts by encouraging transcriptional initiation and inhibition, activating estrogen receptors, and increasing the activity of differentiation, autophagy, inflammation, and blood glucose metabolism. CONCLUSION: Therefore, biochanin-A could be used as a therapeutic drug for various pathological conditions and treatments in human beings.

Carbon Nanostructures As Antibacterials and Active Food-Packaging Materials: A Review.

In this article, we discuss carbon nanoparticles for application as antibacterials and food-packaging materials. The use of petroleum-derived products, synthetic materials, ceramics, wax, etc. in the food-packaging industry emits polluted gas and wastewater, which leads to environmental pollution. To overcome the problems faced by the industry to preserve and package food, carbon nanomaterials may be good alternatives to enhance the shelf life of food without affecting the nutrients. Carbon atoms bond with each other in diverse ways to form many allotropes, resulting in a variety of carbon nanomaterials (CNMs). CNMs include zero-dimensional carbon dots, graphene quantum dots, 1-dimensional carbon nanotubes, 2-dimensional pristine graphene, graphene oxide, reduced graphene oxide, and other derivatives of graphene. Most of the carbon-based nanomaterials are synthesized through a green process that is widely used in the field of food science and technology, and they are used mostly as antibacterial agents and as a biofiller in the development of active food-packaging materials. Carbon nanomaterials (CNMs), viz., carbon dots, graphene, activated carbon-based nanocomposites, carbon nanotubes, etc., are found to be environmentally benign and better materials for food packaging. With antibacterial efficiency, they support food preservation and other applications as well. Thus, carbon nanostructures are found to be applicable as superior materials for food preservation and packaging in modern industry.

Resveratrol: A Vital Therapeutic Agent with Multiple Health Benefits.

Resveratrol (RSV), the most effective stilbene phytoalexin synthesized naturally or induced in plants as part of their defense mechanism, is a key component of natural phenolic compounds and is being considered as a treatment option for a variety of diseases. RSV was discovered in the skin of red grapes, mulberries, peanuts, pines, and Polygonum cuspidatum weed root extracts. It was first extracted from white hellebore (Veratrum grandiflorum O. Loes) roots in 1940, then from Polygonum cuspidatum roots in 1963. However, RSV's use as a drug is limited due to its initial conformational strength and poor stability. The research focused on a set of RSV biological activity data. RSV has been the subject of growing concern, despite its wide range of biological and therapeutic applications. According to the literature, RSV has antioxidant, anti-cancer, cardioprotective, neuroprotective, anti- inflammatory, anti-microbial, immunomodulatory, and radioprotective properties. The current analysis summarized biological applications of RSV, their mechanisms of action, and recent scientific development in the area of their delivery. It is possible to infer that RSV has many effects on infected cells' cellular functions.

Localized Delivery of Drugs through Medical Textiles for Treatment of Burns: A Perspective Approach.

The topical delivery offers numerous benefits, such as the ability to deliver drugs specifically on site selectively, prevents fluctuations in the levels of the drug, improved compliance, and improved self-medication capacity. Skin is the main route of the administration of the drug delivery system (DDS) and burns mainly cause skin damage. A burn is a kind of damage caused to skin and tissues by fire, ice, electrical energy, pollutants, friction, and radiation. There are three different types of burns, including superficial epidermis burns, partial-thickness dermis that stretch to the papillary and reticular dermis, and full-thickness burns that cover the dermis whole. The objective of the present review article is to focus on fabrication techniques of medical textiles, different types of polymers used for designing medicated textiles, skin burn conditions, and application of medicated textiles for treatment of burn along with other applications. Cream, ointment, and gel are the dosage forms used in burns. Intravenous fluids, wound care, assorted antibiotics, surgical and alternative medicines, burned creams and salami, dressings can be used to treat wounds. Nanofibers are nanometer-specific fibers that encapsulate drugs inside them and cure wounds. Nanofibers have all the properties that speed up wound healing. The properties are mechanical integrity, proper timing of wound addiction, temperature homeostasis facilitation and gas exchange, absorption of exudates. The nanofibers have been used in burn care and have been highly efficient and non-toxic.

A Review on Mechanistic and Pharmacological Findings of Diabetic Peripheral Neuropathy including Pharmacotherapy.

BACKGROUND: Chronic hyperglycemia and related complications involving peripheral nerves in diabetes are one of the most severe microvascular complications with an average prevalence of 50-60%. Diabetic neuropathy is among the vascular disorders of diabetes, the most debilitating and crippled, lethal condition impacting patients's quality of life. METHODS: In the present review article, several hypotheses associated with the pathogenesis of Diabetic Peripheral Neuropathy (DPN) have been introduced, among them metabolic pathways associated with polyol pathway, oxidative stress, production of reactive oxygen species (ROS) amplified under chronic hyperglycemic conditions and activation of transcription factor Nuclear factor-κB (NF- κB). The review article also possesses pathogenetic and pharmacologic treatments along with others, including acupressure, lidocaine, and capsaicin for DPN. CONCLUSION: It may be concluded that we can combat the pathogenesis of DPN with different suggested treatments.

Formulation and evaluation of the topical ethosomal gel of melatonin to prevent UV radiation.

BACKGROUND: Clinically, melatonin (MLT) has variable oral absorption and extensive first-pass effect, making its oral mode less preferable. Ethosomes are able to permeate intact through the human skin due to its high deformability. AIM: Present study assessed topical potential of ethosomes loaded with MLT for the prevention of UV radiation. METHODS: Melatonin was encapsulated using different ratios of ethanol, soya lecithin, and cholesterol. Prepared ethosomes were characterized for scanning electron microscopy (SEM), zeta potential, % entrapment efficiency (%EE), in vitro drug release kinetics. Then, optimized formulation was incorporated in gel and evaluated for viscosity, pH, extrudability, homogeneity, skin irritation study, spreadability, in vitro skin permeation study, flux, and stability. RESULTS: Ethosomes were spherical in structure as confirmed by SEM, and zeta potential was in range of -12.4 mV to -27.4 mV. %EE of the vesicles was in the range of 49.61%-78.047%. Cumulative percentage drug release from various ethosomal formulations was ranged from 64.82%-81.01%. F3 was selected as optimized formulation on the basis of highest %EE, zeta potential, and in vitro drug release. An ethosomal gel of optimized formulation F3 was prepared by using carbopol 934 and compared with plain gel formulation. G3 formulation showed pseudoplastic rheological behavior, optimum pH, spreadability and also showed maximum % in vitro drug permeation with flux 13.85 µg/cm2 /hr and followed zero-order release kinetics which was good for topical drug delivery system. CONCLUSION: This research suggested that MLT loaded ethosomes can be potentially used as a topically drug delivery system.

Liposomal delivery of 5 Fluorouracil and Tretinoin: An Aspect of Topical treatment of skin warts / Entrega liposomal de 5 fluorouracilo y tretinoína: un aspecto del tratamiento tópico de las verrugas cutáneas

Background: Tretinoin and 5-fluorouracil are indicated for treatment of various skin disorders and actinic keratosis respectively. Objective: Present study was focused to design liposomes containing 5- fluorouracil and tretinoin. Design was further optimized by 32 full factorial design. Methods: Liposomes were prepared by ethanol injection method and evaluated by Transmission Electron Microscopy, percentage entrapment efficiency, zeta potential and in vitro drug release. Optimized formulation was subjected to histopathological and stability studies at 4ºC, 25ºC and 60ºC temperatures. Results: No drug crystals were visible in transmission electron microscopy, regardless of the preparation technique or the loaded drug. Formulation F9 showed maximum drug entrapment of 72.86% and 69.70% for 5-fluorouraciland tretinoin respectively. When phospholipid concentration was increased from 40 to 60 mg/ml, encapsulation efficiencies of formulation increased. Zeta potential and particle size were maintained within range of -19.14 to -25.61 and 100 to 200 nm respectively which facilitated good stability and penetration of liposomes. Dissolution profiles of formulations F1 to F6 showed high amount of drug release (30.6 to 67.42%) at 2 h. Liposomes were not stable at high temperature but formulations were most stable when stored at lower temperature i.e. 4oC. Conclusion: So, in liposomes both 5-fluorouracil and tretinoin were successfully incorporated and it can be further used for formulation development

Objetivo: El presente estudio se centró en el diseño de liposomas que contenían 5-fluorouracilo y tretinoína. El diseño fue optimizado por 32 diseño factorial completo. Metodos: Los liposomas se prepararon mediante el método de inyección de etanol y se evaluaron mediante Microscopía Electrónica de Transmisión, % de eficiencia de encapsulación, potencial zeta y liberación de fármaco in vitro. La formulación optimizada se sometió a estudios histopatológicos y de estabilidad a temperaturas de 4ºC, 25ºC y 60ºC. Resultados: Ningún cristal de los fármacos era visibles en el Microscopía Electrónica de Transmisión, sin importar la técnica de la preparación o el fármaco cargado. La formulación F9 demostró el atrapamiento máximo del fármaco del 72,86% y del 69,70% para 5-fluorouracilo y tretinoína respectivamente. Cuando la concentración del fosfolípido fue aumentada a partir de 40 a 60 mg/ml, las eficiencias de encapsulación de la formulación aumentaron. El potencial de zeta y el tamaño de partícula fueron mantenidos dentro de la gama de-19,14 a -25,61 y 100 a 200 nanómetros respectivamente, que facilitó la buena estabilidad y la penetración de liposomas. Los perfiles de disolución de las formulaciones F1 a F6 mostraron una alta cantidad de liberación de fármaco (30,6 a 67,42%) a las 2h. Los liposomas no eran estables a alta temperatura, pero las formulaciones eran más estables cuando se almacenaban a una temperatura más baja, es decir, 4 ºC. Concusiones: Así, en los liposomas, tanto los fármacos 5-fluorouracilo como los tretinoína se incorporaron con éxito y se pueden utilizar para el desarrollo de la formulación