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Liposomes, made up of phospholipid bilayers, are efficient nanocarriers for drug delivery because they can encapsulate both hydrophilic and lipophilic drugs. Conventional cancer treatments sometimes involve considerable toxicities and adverse drug reactions (ADRs), which limits their clinical value. Despite liposomes' promise in addressing these concerns, clinical trials have revealed significant limitations, including stability, targeted distribution, and scaling challenges. Recent clinical trials have focused on enhancing liposome formulations to increase therapeutic efficacy while minimizing negative effects. Notably, the approval of liposomal medications like Doxil demonstrates their potential in cancer treatment. However, the intricacy of liposome preparation and the requirement for comprehensive regulatory approval remain substantial impediments. Current clinical trial updates show continued efforts to improve liposome stability, targeting mechanisms, and payload capacity in order to address these issues. The future of liposomal drug delivery in cancer therapy depends on addressing these challenges in order to provide patients with more effective and safer treatment alternatives.
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Mycobacterium tuberculosis (Mtb) has long posed a significant challenge to global public health, resulting in approximately 1.6 million deaths annually. Pulmonary tuberculosis (TB) instigated by Mtb is characterized by extensive lung tissue damage, leading to lesions and dissemination within the tissue matrix. Matrix metalloproteinases (MMPs) exhibit endopeptidase activity, contributing to inflammatory tissue damage and, consequently, morbidity and mortality in TB patients. MMP activities in TB are intricately regulated by various components, including cytokines, chemokines, cell receptors, and growth factors, through intracellular signaling pathways. Primarily, Mtb-infected macrophages induce MMP expression, disrupting the balance between MMPs and tissue inhibitors of metalloproteinases (TIMPs), thereby impairing extracellular matrix (ECM) deposition in the lungs. Recent research underscores the significance of immunomodulatory factors in MMP secretion and granuloma formation during Mtb pathogenesis. Several studies have investigated both the activation and inhibition of MMPs using endogenous MMP inhibitors (i.e., TIMPs) and synthetic inhibitors. However, despite their promising pharmacological potential, few MMP inhibitors have been explored for TB treatment as host-directed therapy. Scientists are exploring novel strategies to enhance TB therapeutic regimens by suppressing MMP activity to mitigate Mtb-associated matrix destruction and reduce TB induced lung inflammation. These strategies include the use of MMP inhibitor molecules alone or in combination with anti-TB drugs. Additionally, there is growing interest in developing novel formulations containing MMP inhibitors or MMP-responsive drug delivery systems to suppress MMPs and release drugs at specific target sites. This review summarizes MMPs' expression and regulation in TB, their role in immune response, and the potential of MMP inhibitors as effective therapeutic targets to alleviate TB immunopathology.
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Inibidores de Metaloproteinases de Matriz , Metaloproteinases da Matriz , Mycobacterium tuberculosis , Humanos , Inibidores de Metaloproteinases de Matriz/farmacologia , Inibidores de Metaloproteinases de Matriz/uso terapêutico , Mycobacterium tuberculosis/efeitos dos fármacos , Metaloproteinases da Matriz/metabolismo , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , Animais , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose/tratamento farmacológico , Progressão da DoençaRESUMO
Patients with rheumatoid arthritis (RA) often have one or more painfuljoints despite adequate medicine. Local drug delivery to the synovial cavity bids for high drug concentration with minimal systemic adverse effects. However, anti-RA drugs show short half-lives in inflamed joints after intra-articular delivery. To improve the therapeutic efficacy, it is essential to ensure that a drug is only released from the formulation when it is needed. In this work, we developed an intelligent "Self-actuating" drug delivery system where Disease-modifying anti-rheumatic Drug (DMARD) methotrexate is incorporated within a matrix intended to be injected directly into joints. This formulation has the property to sense the need and release medication only when joints are inflamed in response to inflammatory enzyme Matrix metalloproteinases (MMP). These enzymes are important proteases in RA pathology, and several MMP are present in augmented levels in synovial fluid and tissues. A high level of MMP present in synovial tissues of RA patients would facilitate the release of drugs in response and ascertain controlled drug release. The formulation is designed to be stable within the joint environment, but to dis-assemble in response to inflammation. The synthesized enzyme-responsive methotrexate (Mtx) encapsulated micron-sized polymer-lipid hybrid hydrogel microspheres (Mtx-PLHM) was physiochemically characterized and tested in synovial fluid, Human Fibroblast like synoviocytes (h-FLS) (derived from RA patients) and a rat arthritic animal model. Mtx-PLHM can self-actuate and augment the release of Mtx drug upon contact with either exogenously added MMP or endogenous MMP present in the synovial fluid of patients with RA. The drug release from the prepared formulation is significantly amplified to several folds in the presence of MMP-2 and MMP-9 enzymes. In the rat arthritic model, Mtx-PLHM showed promising therapeutic results with the significant alleviation of RA symptoms through decrease in joint inflammation, swelling, bone erosion, and joint damage examined by X-ray analysis, histopathology and immune-histology. This drug delivery system would be nontoxic as it releases more drug only during the period of exacerbation of inflammation. This will simultaneously protect patients from unwanted side effects when the disease is inactive and lower the need for repeated joint injections.
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Antirreumáticos , Artrite Reumatoide , Preparações de Ação Retardada , Hidrogéis , Metotrexato , Microesferas , Sinoviócitos , Animais , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/patologia , Humanos , Metotrexato/farmacologia , Metotrexato/uso terapêutico , Metotrexato/química , Metotrexato/administração & dosagem , Hidrogéis/química , Sinoviócitos/efeitos dos fármacos , Sinoviócitos/metabolismo , Sinoviócitos/patologia , Ratos , Antirreumáticos/farmacologia , Antirreumáticos/administração & dosagem , Antirreumáticos/uso terapêutico , Antirreumáticos/farmacocinética , Liberação Controlada de Fármacos , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Masculino , Inflamação/tratamento farmacológico , Inflamação/patologia , Metaloproteinases da Matriz/metabolismo , Líquido Sinovial/efeitos dos fármacos , Líquido Sinovial/metabolismoRESUMO
The advent of drug resistance in response to epidermal growth factor receptor (EGFR)- tyrosine kinase inhibitor (TKI) targeted therapy represents a serious challenge in the management of non-small cell lung cancer (NSCLC). These acquired resistance mutations, attributed to several advanced EGFR mutations and, necessitated the development of new-generation TKIs. Nanomedicine approaches provide a plausible way to address these problems by providing targeted delivery and sustained release, which have demonstrated success in preclinical trials. This review article provides a summary of nano-formulations designed for EGFR-TKI-resistant NSCLC, highlighting their efficacy in both in vitro and in vivo models. These findings reveal insights into the design of nanoparticles and multifunctional nanosystems, offering a potential avenue for efficacious treatment of EGFR-TKIresistant NSCLC.
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Central nervous system tuberculosis (CNS-TB) is a severe form of extra-pulmonary tuberculosis with high mortality and morbidity rates. The standard treatment regimen for CNS-TB parallels that of pulmonary TB, despite the challenge posed by the blood-brain barrier (BBB), which limits the efficacy of first-line anti-TB drugs (ATDs). Nose-to-brain (N2B) drug delivery offers a promising solution for achieving high ATD concentrations directly at infection sites in the brain while bypassing the BBB. This study aimed to develop chitosan nanoparticles encapsulating ATDs, specifically isoniazid (INH) and rifampicin (RIF). These nanoparticles were further processed into micro-sized chitosan nano-aggregates (NA) via spray drying. Both INH-NA and RIF-NA showed strong mucoadhesion and significantly higher permeation rates across RPMI 2650 cells compared to free ATDs. Intranasal administration of these NAs to TB-infected mice for four weeks resulted in a significant reduction of mycobacterial load by approximately â¼2.86 Log 10 CFU compared to the untreated group. This preclinical data highlights the efficacy of intranasal chitosan nano-aggregates in treating CNS-TB, demonstrating high therapeutic potential, and addressing brain inflammation challenges. To our knowledge, this study is the first to show nasal delivery of ATD nano-formulations for CNS-TB management.
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Lung cancer is one of the most fatal malignancies, with the highest death rate (â¼19%), and the NSCLC type accounts for â¼85% of lung cancers. In the search for new treatments, antimicrobial peptides have received much attention due to their propensity for selective destruction of cancer cells. In the current study, we evaluated the efficacy of the metastasis-specific tumour-homing-TMTP1 peptide against lung cancer using inhalable hybrid nano-assemblies of the PEG-PLGA copolymer as a carrier for pulmonary delivery which was assessed for aerodynamic and physicochemical properties, along with the peptide-release profile, physical stability, cellular uptake and biocompatibility, generation of reactive oxygen species, cell migration, autophagic flux, and apoptotic cell death in A549 lung cancer cells. Optimization of inhaled dose, lung retention, and efficacy studies was conducted to evaluate the formulation in an NNK (nicotine-derived nitrosamine ketone) induced tumour-bearing lung cancer murine model. After inhalation, the formulation with nano-scale physiognomies showed good lung deposition, retention, and metabolic stability. The inhalable nano-assemblies have shown enhanced generation of reactive oxygen species with increased autophagy flux and apoptotic cell death. Pre-clinical animal trials show substantial tumour regression by inhalable TMTP1-based nano-formulation with limited side effects. Our results on metastasis targeting and tumour-homing peptide TMTP1 demonstrate its effective tumour targeting and tumour-killing efficacy and provide a reference for the development of new therapeutics for NSCLC.
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Changes in the transition metal homeostasis in the brain are closely linked with Alzheimer's disease (AD), including intraneuronal iron accumulation and extracellular copper and zinc pooling in the amyloid plague. The brain copper, zinc, and iron surplus are commonly acknowledged characteristics of AD, despite disagreements among some. This has led to the theory that oxidative stress resulting from abnormal homeostasis of these transition metals may be a causative explanation behind AD. In the nervous system, the interaction of metals with proteins appears to be an essential variable in the development or suppression of neurodegeneration. Chelation treatment may be an option for treating neurodegeneration induced by transition metal ion dyshomeostasis. Some clinicians even recommend using chelating agents as an adjunct therapy for AD. The current review also looks at the therapeutic strategies that have been attempted, primarily with metal-chelating drugs. Metal buildup in the nervous system, as reported in the AD, could be the result of compensatory mechanisms designed to improve metal availability for physiological functions.
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Rheumatoid arthritis (RA) is the most common form of the chronic inflammatory autoimmune disease characterized by chronic synovitis, synovial proliferation, and cellular infiltration. Further, it leads to bone erosion, destruction of articular cartilage, intense joint pain, swelling, and a high rate of disability, causing an immense load on human health. If the disease is identified early on, and the patient has continuous and timely treatment, many patients can achieve remission. Although research in RA has made considerable progress, conventional therapies are still the most popular treatment options for most people with RA. But, conventional therapies are hampered by various drawbacks, including higher doses, low solubility and permeability, poor bioavailability, a high level of first-pass metabolism, adaptive treatment tolerance (ATT), and long-term drug use. These drawbacks can result in severe side effects and drug toxicity in patients. Advances in polymer science and the application of nanotechnology in drug delivery systems have provided new possibilities in the treatment of RA by developing new-generation smart drug delivery systems (SDDSs). The shortcomings of non-specific drug distribution and uncontrollable drug release by traditional delivery systems have motivated the creation of next-generation SDDSs. These new smart drug delivery treatment methods have significantly changed the course of RA. Such systems can improve drug delivery by virtue of their multi-functionality and targeting capabilities. The ultimate objective of next-generation SDDSs is to deliver medication at the optimal time with precise dosage and efficiency and specificity to the targeted site (such as cells, tissues, and organs), which can aid patients to adhere better to their therapy. This review highlights and discusses the various next-generation SDDSs along with the conventional treatment options available for RA management.
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Artrite Reumatoide , Humanos , Sistemas de Liberação de Medicamentos , Nanotecnologia , Liberação Controlada de Fármacos , SolubilidadeRESUMO
The rise of tuberculosis (TB) superbugs has impeded efforts to control this infectious ailment, and new treatment options are few. Paradoxical Inflammation (PI) is another major problem associated with current anti-TB therapy, which can complicate the treatment and leads to clinical worsening of disease despite a decrease in bacterial burden in the lungs. TB infection is generally accompanied by an intense local inflammatory response which may be critical to TB pathogenesis. Clofazimine (CLF), a second-line anti-TB drug, delineated potential anti-mycobacterial effects in-vitro and in-vivo and also demonstrated anti-inflammatory potential in in-vitro experiments. However, clinical implications may be restricted owing to poor solubility and low bioavailability rendering a suboptimal drug concentration in the target organ. To unravel these issues, nanocrystals of CLF (CLF-NC) were prepared using a microfluidizer® technology, which was further processed into micro-sized CLF nano-clusters (CLF-NCLs) by spray drying technique. This particle engineering offers combined advantages of micron- and nano-scale particles where micron-size (â¼5 µm) promise optimum aerodynamic parameters for the finest lung deposition, and nano-scale dimensions (â¼600 nm) improve the dissolution profile of apparently insoluble clofazimine. An inhalable formulation was evaluated against virulent mycobacterium tuberculosis in in-vitro studies and in mice infected with aerosol TB infection. CLF-NCLs resulted in the significant killing of virulent TB bacteria with a MIC value of â¼0.62 µg/mL, as demonstrated by Resazurin microtiter assay (REMA). In TB-infected mice, inhaled doses of CLF-NCLs equivalent to â¼300 µg and â¼ 600 µg of CLF administered on every alternate day over 30 days significantly reduced the number of bacteria in the lung. With an inhaled dose of â¼600 µg/mice, reduction of mycobacterial colony forming units (CFU) was achieved by â¼1.95 Log10CFU times compared to CLF administered via oral gavage (â¼1.18 Log10CFU). Lung histology scoring showed improved pathogenesis and inflammation in infected animals after 30 days of inhalation dosing of CLF-NCLs. The levels of pro-inflammatory mediators, including cytokines, TNF-α & IL-6, and MMP-2 in bronchoalveolar lavage fluid (BAL-F) and lung tissue homogenates, were attenuated after inhalation treatment. These pre-clinical data suggest inhalable CLF-NCLs are well tolerated, show significant anti-TB activity and apparently able to tackle the challenge of paradoxical chronic lung inflammation in murine TB model.
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Pneumonia , Tuberculose , Camundongos , Animais , Clofazimina/farmacologia , Clofazimina/uso terapêutico , Aerossóis e Gotículas Respiratórios , Tuberculose/tratamento farmacológico , Tuberculose/microbiologia , Pneumonia/tratamento farmacológico , Inflamação/tratamento farmacológicoRESUMO
Obesity is a metabolic disease, which is one of the major causes of morbidity and mortality, where therapeutic options are limited. Treatment of obesity is necessary as it is associated with fatal complications like diabetes mellitus, cardiovascular disease, non-alcoholic fatty liver disease, osteoarthritis, and many more. Liraglutide (Lir), a synthetic analogue of Glucagon-like Peptide-1 (GLP-1), is the FDA approved anti-obesity drug, however, its major limitation is its clinical application which needs frequent parenteral injections. To address the issue of regular injection, we have synthesized a fat fighting oral nano-formulation of liraglutide with a sustained release feature, which was evaluated against high fat diet (HFD) induced obesity in mice. Experimental obesity was induced in mice by feeding HFD for 26 weeks. Lir nanoparticles (NP) were fabricated with chitosan via ion-gelation technique and were coated with Eudragit@S100 to protect the drug in harsh gastric conditions. Physiochemical characterization of Eu-Lir-Cs-NP demonstrated a small particle size of 253.1 ± 1.21 nm with â¼ 9.74 % loading and â¼ 72.11 % encapsulation efficiency of the drug. In-vitro studies showed successful cellular uptake of NP in Caco-2 cells and were stable in various enteric fluid pH conditions. Eudragit@S100 coated chitosan NP were able to protect the drug from harsh gastric pH conditions with more than â¼ 74% of recovery. Treatment of two weeks of liraglutide Eu-Lir-Cs-NP (0.1, 0.2 and 0.4 mg/kg, orally; twice daily) moderately reduces obesity in mice as evidenced by a reduction in the body weight, blood glucose, serum total cholesterol, serum triglyceride, serum resistin and serum insulin level of mice. In addition, significant reduction of liver weight, abdominal white adipose tissue, and hepatic oxidative stress were noted. Our results suggest that chitosan-based NP of liraglutide can be an effective and convenient formulation for the management of obesity.
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Quitosana , Liraglutida , Humanos , Camundongos , Animais , Liraglutida/farmacologia , Liraglutida/uso terapêutico , Células CACO-2 , Ácidos Polimetacrílicos , HipoglicemiantesRESUMO
The high-power radio frequency source for ion cyclotron heating and current drive of ITER tokamak consists of two identical 1.5 MW amplifier chains. These two chains will be combined using a wideband hybrid combiner with adequate coupling flatness, phase balance, return loss, and isolation response to generate 2.5 MW radio frequency (RF) power in the frequency range of 36 to 60 MHz. As part of the in-house development program at ITER-India, a wideband hybrid combiner with coupling flatness and return loss/isolation better than 0.4 and -25 dB, respectively, has been simulated. A detailed analysis for matched load performance of the hybrid combiner for the output power level of 3 MW as well as mismatched load performance for load power of 2.5 MW with voltage standing wave ratio 2.0 and 3.0 MW with voltage standing wave ratio 1.5 has been performed. Based on the simulation, a prototype model was in-house fabricated, and the simulated results have been validated experimentally in splitter and combiner mode. To evaluate performance as a combiner, two solid-state power amplifiers were combined through the prototype combiner for input power levels up to 2.5 kW on matched and mismatched load conditions. In the power splitter experiment, the RF power level up to 1.5 MW from a single amplifier chain was split through the prototype combiner to be dumped in the high power loads in the frequency range of 36 to 60 MHz.
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Tuberculosis (TB) is a highly contagious infection with extensive mortality and morbidity. The rise of TB-superbugs (drug-resistant strains) with the increase of their resistance to conventional antibiotics has prompted a further search for new anti-mycobacterial agents. It is difficult to breach the barriers around TB bacteria, including mycolic cell wall, granuloma, biofilm and mucus, by conventional antibiotics in a short span of time. Hence, there is an essential need for molecules with an unconventional mode of action and structure that can efficiently break the barriers around mycobacterium. Antimicrobial peptides (AMP) are essential components of innate immunity having cationic and amphipathic characteristics. Lines of evidence show that AMPs have good myco-bactericidal and antibiofilm activity against normal as well as antibiotic-resistant TB bacteria. These peptides have shown direct killing of bacteria by membrane lysis and indirect killing by activation of innate immune response in host cells by interacting with the component of the bacterial membrane and intracellular targets through diverse mechanisms. Despite a good anti-mycobacterial activity, some undesirable characteristics are also associated with AMP, including hemolysis, cytotoxicity, susceptibility to proteolysis and poor pharmacokinetic profile, and hence only a few clinical studies have been conducted with these biomolecules. The design of new combinatorial therapies, including AMPs and particulate drug delivery systems, could be new potential alternatives to conventional antibiotics to fight MDR- and XDRTB. This review outlined the array of AMP roles in TB therapy, possible mechanisms of actions, activities, and current advances in pragmatic strategies to improve challenges accompanying the delivery of AMP for tuberculosis therapeutics.
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Peptídeos Antimicrobianos , Tuberculose , Humanos , Antibacterianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/uso terapêutico , Peptídeos Catiônicos Antimicrobianos/química , Bactérias , Tuberculose/tratamento farmacológicoRESUMO
The tumor targeting and stimuli responsiveness behavior of intelligent drug delivery systems imparts effective therapeutic delivery and decreases the toxicity of conventional chemotherapeutic agents in off-target organs. To achieve the receptor targeting and smart drug release, several strategies have been employed to engineer nano-carrier with stimulus sensitivity. In this work, mannose receptor-targeted and matrix metalloproteinase (MMP) responsive gelatin nanoparticles were developed and assessed for its receptor targeting and "on-demand" controlled drug delivery in lung cancer therapeutics. MMPs are protease enzymes and over-expressed in tumorous tissues in all the stages of cancer. The cancer cells also have over-expressed mannose receptors on the cell surface. The surface decoration of gelatin nanoparticles with concanavalin A (con-A) tends to bind with mannose moiety of cell surface glycoproteins which enhances the cancer cell-specific higher uptake of nanoparticles. Gelatin nanoparticles have attracted significant attraction in recent years as a potential drug carrier because of its good biocompatibility and versatile physicochemical properties desirable to deliver the drug. Cisplatin was complexed with the gelatin matrix (CG-NP) to evaluate stimuli responsiveness with the lung cancer cells and its release pattern. In this smart inhalable delivery system, cisplatin loaded gelatin nanoparticles were surface decorated with con-A (CCG-NP). In tumorous cells, con-A coating is expected to enhance mannose receptor-specific cellular internalization of CCG-NP, and subsequently high level of MMP in tumor tissues would help to release cisplatin in response and ensures controlled drug release. The synthesized CCG-NP has shown enzyme triggered drug release and favorable endocytosis after incubation of 12 h compare to uncoated nanoparticles. The efficacy of CCG-NP significantly increased in presence of MMP-2 enzyme in lung cancer cell line A549 cells. It also significantly enhanced reactive oxygen species generation, cell cycle arrest in S and G2/M phase, and apoptosis in cancer cells. Therefore, inhalable CCG-NP promises a pragmatic approach to construct a receptor targeting and an "on-demand" drug delivery system to efficiently deliver the drug at the tumor site only.
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Nanopartículas , Neoplasias , Linhagem Celular Tumoral , Concanavalina A , Portadores de Fármacos , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Gelatina , Neoplasias/tratamento farmacológicoRESUMO
BACKGROUND: Phyllanthus species exhibit a wide range of in vitro and in vivo pharmacological activities; however, little is known about the compounds present in the extracts that are responsible for such actions. OBJECTIVE: Development and validation of a simple reversed phase HPLC-PDA method for profiling of phyllanthin, hypophyllanthin, nirtetralin, and niranthin in extracts of Phyllanthus species was carried out. METHODS: Separation was achieved using an XBridge column® (150 × 4.6 mm, 5.0 µm id) in an isocratic elution mode with mobile phase comprising of a mixture of acetonitrile and water with TFA (0.05%, v/v, pH = 2.15) at ambient temperature with a flow rate of 1 mL/min. RESULTS: Phyllanthin, hypophyllanthin, nirtetralin, and niranthin were eluted at mean retention times of 10.47, 11.10, 13.67, and 14.53 min, respectively. LOD and LOQ for all four analytes were 0.75 and 3.00 µg/mL, respectively. RSDr values for intraday and interday precision for phyllanthin, hypophyllanthin, nirtetralin, and niranthin were 0.38-1.32 and 0.45-1.77%; 0.22-3.69 and 0.24-3.04%, 0.73-2.37 and 0.09-0.31%, and 1.56-2.77 and 0.12-0.68%, respectively. CONCLUSIONS: The developed and validated HPLC-PDA method was applied for identification and quantification of phyllanthin, hypophyllanthin, nirtetralin, and niranthin in extracts of different plant parts of selected Phyllanthus species. The outcome of the present investigation could be useful for selection of best species to promote its commercial cultivation and suitable extraction solvent for preparation of lignan-enriched fractions. This HPLC-PDA method could be useful for quality control of herbal formulations containing plants from Phyllanthus species.
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Lignanas , Phyllanthus , Anisóis , Cromatografia Líquida de Alta Pressão , Dioxóis , Índia , Extratos VegetaisRESUMO
Animal production has a key role in global economic development and food security. Ticks, specifically Rhipicephalus microplus cause substantial economic and health impacts on more than eighty percent of the world cattle population. Though synthetic acaricides play a major role in tick management, their injudicious usage has caused environmental pollution and also promote the establishment of multi-acaricide resistant tick populations which is a matter of great concern. To provide an effective tool for controlling these resistant ticks, the present work was aimed to develop safe and inexpensive antitick natural formulations. Our bioprospection studies of Ageratum conyzoides plant established it as a species potentially having strong acaricidal activity due to the presence of potent acaricidal phyto-chemicals. To develop a suitable antitick natural formulation, 41 samples/fractions/formulations were prepared from the dry powder of the whole aerial part of the A. conyzoides plant using different techniques and delivery matrices. The strongest antitick effect was recorded for formulation ACF6, which demonstrated 87 ± 6% mean mortality with 57 % inhibition of oviposition in treated female ticks. Ticks treated with the ACF6 formulation showed a significant (p < 0.001) reduction in cuticular protein (1.238 ± 0.01 mg/mL) as compared to control ticks (2.928 ± 0.01 mg/mL) but no significant difference in chitin content of treated ticks and control ticks was observed. The formulation was found safe in a rat model as no significant differences in biochemical and haematological parameters among treated and control rats were noted. Histopathological studies indicated no sign of hepatocellular necrosis and no significant changes in the weights of liver and spleen was recorded. The overall in vivo efficacy of the formulation was 85 % for experimentally infested cattle with direct mortality of more than 80 % within 96 h post-application. The lethal effect of the formulation was in the form of drying and dead ticks 1-2 d after application. The developed formulation has the potential to be adopted as an alternative tick control measure in an ecofriendly manner.
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Acaricidas , Ageratum/química , Doenças dos Bovinos/prevenção & controle , Resistência a Medicamentos , Extratos Vegetais , Rhipicephalus , Controle de Ácaros e Carrapatos , Infestações por Carrapato/veterinária , Animais , Bovinos , Doenças dos Bovinos/parasitologia , Feminino , Larva/efeitos dos fármacos , Larva/crescimento & desenvolvimento , Masculino , Rhipicephalus/efeitos dos fármacos , Rhipicephalus/crescimento & desenvolvimento , Infestações por Carrapato/parasitologia , Infestações por Carrapato/prevenção & controleRESUMO
BACKGROUND: Ageratum conyzoides is an aromatic plant. It is considered as an invasive and cosmopolite weed, widely spread in tropical and subtropical regions. Phytochemicals such as benzopyrenes, flavonoids, and terpenoids are reported from A. conyzoides. OBJECTIVE: Development and validation of a reversed-phase HPLC-photodiode array (PDA) detection method for simultaneous identification and quantification of coumarin, precocene-I, ß-caryophyllene oxide, α-humulene, and ß-caryophyllene in extracts of A. conyzoides and essential oils was carried out. METHODS: Separation of analytes was achieved on a RP-18 (250 mm × 4.6 mm, 5 µm) column using a solvent system comprising of a mixture of acetonitrile and water with 0.05% trifluoroacetic acid in gradient elution mode at ambient temperature with flow rate of 1 mL/min. RESULTS: The retention time of coumarin, precocene-I, ß-caryophyllene oxide, α-humulene, and ß-caryophyllene was 4.38, 12.86, 20.10, 33.34, and 35.11 min, respectively. Limits of detection for coumarin, precocene-I, ß-caryophyllene oxide, α-humulene, and ß-caryophyllene were 2.5, 2.5, 2.5, 0.025, and 2.5 µg/mL, respectively. Similarly, LOQ were 10, 10, 10, 0.10, and 10 µg/mL for coumarin, precocene-I, ß-caryophyllene oxide, α-humulene, and ß- caryophyllene, respectively. Repeatabilities (RSD, %) values for intraday and interday precision for coumarin, precocene-I, ß-caryophyllene oxide, α-humulene, and ß-caryophyllene was 0.765-2.086 and 0.886-2.128; 0.879-1.672 and 0.979-1.825; 0.696-2.418 and 0.768-2.592; 1.728-2.362 and 1.965-2.378; 1.615-2.897 and 1.658-2.906, respectively. CONCLUSIONS: The separation of five analytes was achieved within 50 min. The developed and validated HPLC-PDA method was successfully applied for identification and quantification of above five analytes in A. conyzoides extracts and essential oils. The method could be used for meeting the characterization criteria of phytoformulations.
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Ageratum , Óleos Voláteis , Cromatografia Líquida de Alta Pressão , Cumarínicos , Sesquiterpenos Monocíclicos , Extratos Vegetais , Sesquiterpenos PolicíclicosRESUMO
Background: Xanthones and polyisoprenylated benzophenones (PIBs) are two important classes of plant secondary metabolites with a wide range of bioactivities. Garcinia species synthesize numerous xanthones and PIBs. As per the literature, no data claiming simultaneous identification and quantification of three xanthones, α-mangostin, ß-mangostin, γ-mangostin, and two PIBs, xanthochymol, isoxanthochymol, were found. Methods: A validated ultra-HPLC (UHPLC)-photodiode array (PDA) method for the simultaneous identification and quantification of five compounds in different extracts of eight Indian Garcinia species was developed. The compounds were separated on a Waters ACQUITY™ UPLC H-Class column using a mobile phase consisting of solvents 0.1% formic acid in water (A) and methanol (B) in gradient elution mode. The total run time was 9 min. Results: From fruit rinds of eight Indian Garcinia species, namely Garcinia cambogia, G. cowa, G. indica, G. loniceroides, G. mangostana, G. morella, G. pedunculata, and G. xanthochymus, extracts were prepared using solvents of varying polarity. These extracts were analyzed for five biologically important compounds, namely α-mangostin, ß-mangostin, γ-mangostin, xanthochymol, and isoxanthochymol. The results revealed that there is a wide variation in concentration of these compounds in extracts of Garcinia species. Conclusions: The developed and validated UHPLC-PDA method could be used for simultaneous identification and quantification of these five compounds for bioprospection of other Garcinia species.
Assuntos
Benzofenonas/análise , Garcinia/química , Xantonas/análise , Cromatografia Líquida de Alta Pressão/métodosRESUMO
Background: Both the roots and leaves of Withania somnifera are products of commerce. They contain active compounds of therapeutic value and mostly different withanolides. Several pharmacological activities of W. somnifera have links to one or more withanolides. The presence of phenolic compounds in extracts could play a vital role in the reduction of blood glucose levels in diabetic subjects. Objective: The present study was carried out for the selection of a solvent to prepare extracts rich in phenolics, withaferin A (WA), 12-deoxywithastromonolide (12WD), and withanolide A (WDA). A simple, rapid HPLC method was also developed for the identification and quantification of WA, 12WD, and WDA. Methods: The extraction efficiency of aqueous alcoholic solvents including hexane, chloroform, ethyl acetate, and methanol were compared for three selected withanolides and total phenolic content. The contents of WA, 12WD, and WDA and total phenolics were determined in the extracts. The quality of nine formulations containing W. sominfera were also compared in terms of the content of WA, 12WD, and WDA and total phenolics. Results: The maximum extract yield and the total withanolide and phenolic content were obtained from aqueous alcoholic compositions at 50:50 (v/v), 70:30 (v/v), and 100:0 (v/v), respectively. In the case of organic solvents, chloroform and ethyl acetate yielded the highest concentrations of phenolics and three withanolides, respectively. The total phenolic content in formulations was in the range of 1.84-3.13%, and total withanolide content showed wide variability. Conclusions: The outcome of the present investigation could be utilized for the selection of extraction solvents to prepare W. somnifera-enriched extracts and their quality monitoring by using the developed and validated HPLC-Photodiode array detection method. Highlights: A process for preparation of phenolics and withanolides (withaferin A, 12-deoxywithastramonolide and withanolide A) enriched extracts of Withania somnifera. Simple and rapid HPLC method was also developed and validated as per the ICH guidelines for identification and quantification of three major withanolides. The developed HPLC method was applied to analyze the quality of extracts and marketed herbal products (mono, as well as poly constituents). Optimized extraction process could be utilized for upscaling process development in preparation of enriched extracts from Withania somnifera, crop improvement, bio-prospection studies and quality control.
Assuntos
Fenóis/isolamento & purificação , Raízes de Plantas/química , Withania/química , Vitanolídeos/isolamento & purificação , Cromatografia Líquida de Alta Pressão , Limite de Detecção , Fenóis/análise , Reprodutibilidade dos Testes , Solventes , Vitanolídeos/análiseRESUMO
The objective of the present investigation was to optimize extraction conditions for maximum recovery of bioactive phenolics from different parts of Saraca asoca. Extraction recovery was optimized using a mixture of methanol and water in different proportions. For identification and quantification of six analytes, a rapid reversed phase ultra-performance liquid chromatography (UPLC) photo diode array detection method was developed. UPLC separation was achieved in a gradient elution mode on a C18 column with acetonitrile and aqueous phosphoric acid (0.1%, pH = 2.5). Extraction solvent for maximum recovery of analytes varied depending on the nature of matrices. The developed UPLC method was validated in accordance with International Council for Harmonisation (ICH) guidelines. Wide linearity range, sensitivity, accuracy, short retention time, and simple mobile phase composition implied that the method could be suitable for routine analysis of all six analytes with high precision and accuracy. The uniqueness of this study is the determination of the distribution of these compounds in the various parts of S. asoca.
Assuntos
Fabaceae , Catequina/análogos & derivados , Cromatografia Líquida de Alta Pressão , Ácido Gálico , Proantocianidinas , Reprodutibilidade dos Testes , Extração em Fase Sólida , Espectrometria de Massas em TandemRESUMO
Senna is an important medicinal plant and is used in many Ayurvedic formulations. Dianthraquinone glucosides are the main bioactive phytochemicals present in leaves and pods of senna. The extraction efficiency in terms of yield and composition of the extract of senna prepared using both conventional (cold percolation at room temperature and refluxing) and non conventional (ultrasound and microwave assisted solvent extraction as well as supercritical fluid extraction) techniques were compared in the present study. Also a rapid reverse phase HPLC-PDA detection method was developed and validated for the simultaneous determination of sennoside A and sennoside B in the different extracts of senna leaves. Ultrasound and microwave assisted solvent extraction techniques were more effective in terms of yield and composition of the extracts compared to cold percolation at room temperature and refluxing methods of extraction.