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

Cybersecurity In The Age Of Artificial Intelligence – Who Should Be Culpable?

  The age of the AI has come in hurtling and it has become difficult for law makers to keep pace. At the same time, unbridled by legislations, criminals in the cyber space are using these Artificial Intelligence tools. The instances of ChatGPT’s use in writing academic articles to morphing pictures of people, the degree of seriousness is high. Another incident was the use of morphed pictures of a celebrity couple’s child for disseminating fake news. The lines of reality and morphed is blurring to an extent that the line is very unclear and hence it is essential that proper laws are put in place to identify and assign culpability to the use of AI for criminal activities. Although the AI applications are guided by moral codes, the said moral codes would be guided by the developer’s morals and hence the question of standardized laws, ethics and morals would arise here. While the debate around AI and intellectual property rights have been on the round for some time and Courts in certain jurisdictions have already deliberated on it, the question has shifted to criminal culpability in case of hacking, creation of photos that falsify evidence, publication of pictures of individuals that have been digitally altered via AI, etc. The question that arises is who is in control of the actions of the AI, since the creator of the AI is not always the person who is involved in criminal activities that are affected through the AI. Also, would a standard code of ethics be able to govern the AI’s functioning successfully

Extended release promethazine HCl using acrylic polymers by freeze-drying and spray-drying techniques: formulation considerations

The present study investigated a novel extended release system of promethazine hydrochloride (PHC) with acrylic polymers Eudragit RL100 and Eudragit S100 in different weight ratios (1:1 and 1: 5), and in combination (0.5+1.5), using freeze-drying and spray-drying techniques. Solid dispersions were characterized by Fourier-transformed infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), Powder X-ray diffractometry (PXRD), Nuclear magnetic resonance (NMR), Scanning electron microscopy (SEM), as well as solubility and in vitro dissolution studies in 0.1 N HCl (pH 1.2), double-distilled water and phosphate buffer (pH 7.4). Adsorption tests from drug solution to solid polymers were also performed. A selected solid dispersion system was developed into capsule dosage form and evaluated for in vitro dissolution studies. The progressive disappearance of drug peaks in thermotropic profiles of spray-dried dispersions were related to increasing amount of polymers, while SEM studies suggested homogenous dispersion of drug in polymer. Eudragit RL100 had a greater adsorptive capacity than Eudragit S100, and thus its combination in (0.5+1.5) for S100 and RL 100 exhibited a higher dissolution rate with 97.14% drug release for twelve hours. Among different formulations, capsules prepared by combination of acrylic polymers using spray-drying (1:0.5 + 1.5) displayed extended release of drug for twelve hours with 96.87% release followed by zero order kinetics (r²= 0.9986).O presente trabalho compreendeu estudo de um novo sistema de liberação prolongada de cloridrato de prometazina (PHC) com polímeros acrílicos Eudragit RL100 e Eudragit S100 em diferentes proporções em massa (1:1 e 1:5) e em combinação (0,5+1,5), utilizando técnicas de liofilização e de secagem por aspersão As dispersões sólidas foram caracterizadas por espectrofotometria no infravermelho por transformada de Fourier (FT-IR), calorimetria diferencial de varredura (DSC), difratometria de raios X (PXRD), Ressonância Magnética Nuclear (RMN), microscopia eletrônica de varredura (SEM) e, também, por estudos de solubilidade e de dissolução in vitro em HCl 0,1 N (pH 1,2), água bidestilada e tampão fosfato (pH 7,4). Realizaram-se, também, testes de adsorção da solução do fármaco nos polímeros sólidos. Desenvolveu-se sistema de dispersão sólida exclusiva dentro das cápsulas, que foi avaliado por meio de estudos de dissolução in vitro. Relacionou-se o desaparecimento progressivo de picos do fármaco em perfis termotrópicos de dispersões secas por spray à quantidade aumentada de polímero, enquanto os estudos de SEM sugeriram dispersão homogênea do fármaco no polímero. O Eudragit RL100 apresentou maior capacidade de adsorção do que o Eudragit S100 e, dessa forma, a combinação de (0,5+1,5) para S100 e para RL100 mostrou taxa de dissolução maior, com liberação de 94,17% de fármaco em 12 horas. Entre as várias formulações, as cápsulas preparadas pela combinação de polímeros acrílicos utilizando secagem por aspersão (0,5+1,5) apresentou liberação prolongada do fármaco em 12 horas, com 96,78% de liberação, seguindo cinética de ordem zero (r² = 0,9986

VERSATILE RP-HPLC METHOD DEVELOPMENT FOR QUANTITATIVE ESTIMATION OF TELMISARTAN AND RAMIPRIL IN ANIMAL PLASMA

Objective: A fast, specific, and sensitive high-performance liquid chromatographic method has been developed and validated for the quantitative determination of unchanged Ramipril (RAM) and Telmisartan (TEL) in animal plasma.Methods: Analytes were extracted from animal plasma, 250 µl of animal plasma sample were mixed with internal working standard (25 ngmL-1) with the further addition of chloroform (HPLC Grade, Merck). The clear organic layer was separated and reconstituted to 1 ml in mobile phase and analysed by HPLC. The method was validated and evaluated in terms of linearity, accuracy, precision, specificity, limit of detection and limit of quantitation.Results: Absorption maxima of TEL and RAM was found to be 270 and 273 nm respectively. TEL and RAM with their respective internal standards (I. S.) were found to be well separated from the co-eluted components and there were no interferences from the endogenous material. The limit of detection (LOD) and limit of quantitation (LOQ) were found to be 2.01±.05; 4.88±0.10 and 0.11 and 0.25 for TEL and RAM respectively on the basis of a signal to noise ratio. The ruggedness of the method at various parameters was found to be±1.94% and±1.02% for TEL and RAM respectively. The low values of %RSD (<2.0) for each of the drug proposed that during all deliberate variations, middle-quality control (MQC) was not affected and it was in accordance with that of actual.Conclusion: Thus developed High-Performance Liquid Chromatography (HPLC) method was found to be more accurate, precise, sensitive, selective and reproducible

NEUROPHARMACOLOGICAL EFFECTS OF THE ETHANOLIC EXTRACT OF DERIVATIVES OF LUPEOL IN RATS

Objective: The neuropharmacological activities of ethanolic extract derivatives of lupeol are being screened on rats. Prepared derivatives are evaluated for their locomotor, anxiolytic and stereotype activities. The present investigation was designed to evaluate the antipsychotic effect of semisynthetic derivatives of lupeol using rat models of elevated maze model and apomorphine-induced stereotype behavior.Methods: Lupeol was extracted from Crataeva nurvala bark using ethano. After chemical modification, we made different derivatives using aldol condensation. Different derivatives were obtained from a series of reaction previously published LAH-3, LAP-3, LAPEA-3, LAMP-3, LATS-3, and LAS-3. Neuropharmacological effects, including anxiolytic, central nervous inhibitory, and stereotype antipsychotic effects were evaluated in the different derivatives of lupeol at a dose of 250 mg/kg using standard methods.Results: The absolute derivatives of LAH3 and LAPEA3 showed a significant reduction in the activity score in actophotometer test. Reduction in the locomotor activity indicates central nervous system (CNS) depressant property of the drug. LAMP3 and LAS3 show a significant anxiolytic effect. From the result of elevated plus maze, it was evident that derivatives of lupeol treated animals exhibit an increased number of entries into open arm when compared to normal control, which shows the anxiolytic activity of the lupeol derivatives. Sniffing, rearing and licking activities for lupeol derivatives LAH3 and LAPEA3 were found to be 35%, 33%, and 40% and 40.33%, 38%, and 33.33% respectively when it compared with standard and control groups. This model is suggestive of the absence of negative symptoms alleviating property of all the treatment groups.Conclusions: The lupeol and its semisynthetic derivatives possess anxiolytic, CNS inhibitory, and antipsychotic effects to varying degree

The Legal Dynamics of E-Commerce and Direct Selling: A Comprehensive Analysis of The Amway India Enterprises Vs. Union of India Case

This research paper delves into the landmark case of Amway India Enterprises vs. Union of India, adjudicated by the Delhi High Court in July 2019. The case pertained to alleged interference by e-commerce giants such as Amazon and Flipkart in the contractual relationships between direct selling companies and their independent sales representatives. The paper dissects the intricate legal facets of this case, encompassing constitutional matters, intellectual property rights, information technology laws, consumer protection, and contractual and tort laws. A central issue examined was whether e-commerce platforms were bound by the Direct Selling Guidelines, 2016, and if their actions constituted trademark violations. The case also probed the applicability of Section 79 of the Information Technology Act and intermediary responsibilities. The Delhi High Court's judgment wielded substantial influence over the Indian business landscape. E-commerce platforms were mandated to cease commercial activity on plaintiffs' products and furnish detailed seller data, necessitating operational adjustments. In conclusion, the Amway India Enterprises case signifies the evolving commerce dynamics in the digital era and underscores the pivotal role of the legal system in ensuring fair competition, consumer safety, and intellectual property preservation. As business landscapes evolve, this case illuminates the path toward a responsible, transparent, and secure online marketplace in India

Public-Private Partnerships in Education: A Comprehensive Study of The Right to Education in India

This research article explores the evolving landscape of education in India, focusing on the critical role of Public-Private Partnerships (PPPs) in the context of the Right to Education Act. India's government schools face resource constraints, prompting increased private sector involvement in education. This article discusses the impact of PPPs on education access, equity, and quality, drawing on a field survey conducted in Vadodara. Demographically, the survey reveals heightened awareness of the Right to Education Act, especially among women, underscoring its importance. An overwhelming majority recognizes PPPs' role in enhancing education but highlights the need for greater awareness regarding the nuances of these partnerships. Additionally, opinions vary on the adequacy of the Act's 25% reservation policy, signalling potential room for improvement. Teachers' perspectives showcase widespread compliance with reservation policies in public schools. Yet, concerns arise over private school reservations' efficacy. Respondents emphasize the Act's positive impact on education quality, affordability, and infrastructure, underscoring the comprehensive demand for improved educational access. However, doubts linger regarding PPPs potentially exacerbating educational inequalities, challenging competition, and privatizing the sector. Clear policies and safeguards are imperative to address these concerns. In sum, this research underscores the transformative potential of PPPs in realizing the Right to Education, while advocating for greater awareness, policy refinement, and equitable outcomes to ensure quality education for all in India

Enteric coated HPMC capsules plugged with 5-FU loaded microsponges: a potential approach for treatment of colon cancer

The work was aimed at developing novel enteric coated HPMC capsules (ECHC) plugged with 5 Florouracil (5-FU) loaded Microsponges in combination with calcium pectinate beads. Modified quasi-emulsion solvent diffusion method was used to formulate microsponges based on 32 factorial design and the effects of independent variables (volume of organic solvent and Eudragit RS100 content) on the dependent variables (Particle size, %EE & % CDR) were determined. The optimized microsponges (F4) were characterized by SEM, PXRD, TGA and were plugged along with calcium pectinate beads in HPMC capsules and the HPMC capsules were further coated with enteric polymer Eudragit L 100 (Ed-L100) and/ or Eudrgit S 100 (Ed-S 100) in different proportions. In vitro release study of ECHC was performed in various release media sequentially SGF for 2 h, followed by SIF for the next 6 h and then in SCF (in the presence and absence of pectinase enzyme for further 16 h). Drug release was retarded on coating with EdS-100 in comparison to blend of EdS-100: EdL-100 coating. The percentage of 5-FU released at the end of 24 h from ECHC 3 was 97.83 ± 0.12% in the presence of pectinase whereas in control study it was 40.08 ± 0.02% drug. The optimized formulation was subjected to in vivo Roentgenographic studies in New Zealand white rabbits to analyze the in vivo behavior of the developed colon targeted capsules. Pharmacokinetic studies in New Zealand white rabbits were conducted to determine the extent of systemic exposure provided by the developed formulation in comparison to 5-FU aqueous solutions. Thus, enteric coated HPMC capsules plugged with 5-FU loaded microsponges and calcium pectinate beads proved to be promising dosage form for colon targeted drug delivery to treat colorectal cancer.O trabalho teve como objetivo o desenvolvimento de novas cápsulas com revestimento entérico HPMC (ECHC) conectadas com microesponjas carregadas com fluoruracila (5-FU) em combinação com grânuos de pectinato de cálcio. O método de difusão de solvente modificado quasi-emulsão foi usado para formular microesponjas com base no planejamento fatorial 32 e determinaram-se os efeitos das variáveis independentes (volume de solvente orgânico e conteúdo Eudragit RS100) sobre as variáveis dependentes (tamanho de partícula, EE% e % CDR). As microesponjas otimizadas (F4) foram caracterizadas por SEM, PXRD, TGA e ligadas aos grânulos de pectinato de cálcio em cápsulas de HPMC e estas foram, ainda, revestidas com polímero entérico Eudragit L 100 (Ed-L100) e/ou Eudrgit S 100 (Ed S 100) em diferentes proporções. No estudo de liberação in vitro de ECHC foi realizada em vários meios de liberação sequencial SGF durante 2 h, seguido de SIF para as próximas 6 h, e, em seguida, em SCF (na presença e na ausência de enzima pectinase por mais 16 h). A liberação do fármaco foi retardada em revestimento com a EDS-100, em comparação com mistura de EDS-100: EDL-100, de revestimento. O percentual de 5-FU liberado de ECHC 3 ao final de 24 h foi 97,83 ± 0,12% em presença de pectinase, enquanto que para o controle foi de 40,08 ± 0,02% do fármaco. A formulação otimizada foi submetida a estudos Roentgenográficos in vivo, em coelhos brancos Nova Zelândia, para analisar o comportamento das cápsulas desenvolvidas direcionadas ao cólon. Os estudos de farmacocinética em coelhos brancos da Nova Zelândia foram conduzidos para determinar a extensão da exposição sistêmica propiciada pela formulação desenvolvida, em comparação com solução aquosa de 5-FU. Assim, cápsulas entéricas de HPMC revestidas e conectadas com microesponjas carregadas com 5-FU e grânulos de pectinato de cálcio se mostraram promissoras como formulação para liberação do fármaco no cólon no tratamento do câncer colorretal

Primary and novel approaches for colon targeted drug delivery – A review

The colon is a site where both local and systemic delivery of drugs can take place. Local delivery could, for example, allow topical treatment of inflammatory bowel disease. Treatment could be made more effective if it were possible for drugs to be targeted directly on the colon. Systemic side effects could also be reduced. Colon specific systems might also allow oral administration of peptide and protein drugs, which are normally inactivated in the upper parts of the gastrointestinal tract. Primary approaches for CDDS (Colon Specific Drug Delivery), which includes prodrugs, pH and time dependent systems and microbially triggered drug delivery system achieved limited success and having limitations. Newly developed CDDS, which includes pressure controlled colonic delivery capsules (PCDCS), CODESTM and osmotic controlled drug delivery are unique in terms of achieving in vivo site specificity and feasibility of manufacturing process. This review also focuses on evaluations of CDDS in general.Keywords: Colon drug delivery systems; Primary approaches; Newly developed approaches; evaluation of colon targeted drug delivery system

Diversity of water-borne conidial fungi in some freshwater bodies of Kumaun Himalaya in district Nainital (Uttarakhand), India

The aquatic ecosystem harbours a variety of micro-organisms, among which water-borne conidial fungi occupy an important place. Their occurrence in freshwater habitat has great significance in the decomposition of submerged plant materials, nutrient release and productivity. Their occurrence and frequency to extreme temperatures and pH may have a profound effect on fungal community composition and metabolic activities. The present paper deals with the diversity of conidial aquatic fungi from different unexplored freshwater bodies flowing through different elevations (1000-1500 m) in district Nainital, Kumaun Himalaya. Comparative study of species composition in different seasons, sporulation temperatures and pH conditions was also carried out. In all, 18 species of conidial fungi belonging to 14 genera were recorded, out of which maximum species (11 species) were recorded in both rainy (July to September) and winter seasons (November to December). Anguillospora crassa, Beltrania rhombica, Campylospora chaetocladia, Cylindrocarpon aquaticum, Helicomyces roseus and Tetracladium setigerum were isolated only during rainy season; Alatospora acuminata, Clavariopsis aquatica, Clavatospora tentacula, Lemonniera pseudofloscula, L. terrestris and Tetrachaetum elegans were isolated only during winter season while Lunulospora curvula, L. cymbiformis, Setosynnema isthmosporum, Tetracladium marchalianum and Triscelophorus acuminatus were isolated in both rainy and winter seasons. The preferred pH and the sporulation temperature ranged from 6-7 and 15-20 °? respectively. The results of the present study are clearly indicating fungal species composition variations along pH, temperature, seasonal and altitudinal gradients and the sites selected for this exploratory investigation are being undertaken for the first time