Role of Amphotericin B in the Treatment of Mucormycosis.

BACKGROUND: Regardless of the most recent inclusion of mold-active agents (isavuconazole and posaconazole) to antifungal agents against mucormycosis, in conjunction with amphotericin B (AMB) items, numerous uncertainties still exist regarding the treatment of this rare infection. The order Mucorales contains a variety of fungi that cause the serious but uncommon fungal illness known as mucormycosis. The moulds are prevalent in nature and typically do not pose significant risks to people. Immunocompromised people are affected by it. OBJECTIVE: This article's primary goal is to highlight the integral role that AMB plays in this condition. METHODS: Like sinusitis (including pansinusitis, rhino-orbital, or rhino-cerebral sinusitis) is one of the many signs and symptoms of mucormycosis. The National Center for Biotechnology Information (NCBI) produces a variety of online information resources for review articles on the topic-based mucormycosis, AMB, diagnosis of mucormycosis and the PubMed® database of citations and abstracts published in life science journals. These resources can be accessed through the NCBI home page at https://www.ncbi.nlm.nih.gov. RESULTS: The article provides a summary of the pharmacological attributes of the various AMB compositions accessible for systemic use. CONCLUSION: The article demonstrates the traits of the drug associated with its chemical, pharmacokinetics, stability, and other features, and illustrates their most useful characteristics for clinical application.

Artificial Intelligence for Computer-Aided Drug Discovery.

The continuous implementation of Artificial Intelligence (AI) in multiple scientific domains and the rapid advancement in computer software and hardware, along with other parameters, have rapidly fuelled this development. The technology can contribute effectively in solving many challenges and constraints in the traditional development of the drug. Traditionally, large-scale chemical libraries are screened to find one promising medicine. In recent years, more reasonable structure-based drug design approaches have avoided the first screening phases while still requiring chemists to design, synthesize, and test a wide range of compounds to produce possible novel medications. The process of turning a promising chemical into a medicinal candidate can be expensive and time-consuming. Additionally, a new medication candidate may still fail in clinical trials even after demonstrating promise in laboratory research. In fact, less than 10% of medication candidates that undergo Phase I trials really reach the market. As a consequence, the unmatched data processing power of AI systems may expedite and enhance the drug development process in four different ways: by opening up links to novel biological systems, superior or distinctive chemistry, greater success rates, and faster and less expensive innovation trials. Since these technologies may be used to address a variety of discovery scenarios and biological targets, it is essential to comprehend and distinguish between use cases. As a result, we have emphasized how AI may be used in a variety of areas of the pharmaceutical sciences, including in-depth opportunities for drug research and development.

Effect of Propranolol Prophylaxis on Headache Frequency in Children with Migraine Without Aura: A Randomized, Double-Blind, Placebo-Controlled Trial.

OBJECTIVE: To compare the efficacy of propranolol prophylaxis with placebo on headache frequency in children with migraine over the 3-mo follow-up. METHODS: In this randomized, double-blind, placebo-controlled trial children aged 6-12 y with newly diagnosed migraine without aura as per the International Classification for Headache Disorders, 3rd edition (ICHD-3) criteria were enroled. They were randomized to the intervention group receiving oral propranolol (1-3 mg/kg/d, BID) and the control group receiving a similar looking, inert, oral placebo for migraine prophylaxis for 3 mo. The number of migraine attacks over the 3-mo follow-up (using a headache diary) was the primary outcome. Pediatric Migraine Disability Assessment Scale (PedMIDAS) was used for assessing disability and Visual analogue scale was used for assessing headache severity. Analysis was done on intention-to-treat basis. RESULTS: Twenty children (10 in each group) completed the study. The two groups were similar at baseline. Both the study drugs produced significant reduction of headache frequency after the study intervention (p = 0.002). However, there was no difference between the two groups with respect to either the median (IQR) number of headache attacks [22 (20, 25) vs. 14 (10, 20); p = 0.05], headache severity [1 (0, 1) vs. 0.5 (0, 1); p = 0.48] or migraine disability [39.5 (28, 44) vs. 35 (22, 38); p = 0.27]. Adverse effects were higher in the intervention group (p = 0.52). CONCLUSIONS: Propranolol was effective for migraine prophylaxis in children but the effect was not higher than placebo. Larger placebo-controlled trials of propranolol need to be conducted to decide its place in migraine prophylaxis in children. TRIAL REGISTRATION: Thailand Clinical Trials Registry; TCTR20200621001.

An Overview of Green Synthesis and Potential Pharmaceutical Applications of Nanoparticles as Targeted Drug Delivery System in Biomedicines.

Nanotechnology-based nanomedicine offers several benefits over conventional forms of therapeutic agents. Moreover, nanomedicine has become a potential candidate for targeting therapeutic agents at specific sites. However, nanomedicine prepared by synthetic methods may produce unwanted toxic effects. Due to their nanosize range, nanoparticles can easily reach the reticuloendothelial system and may produce unwanted systemic effects. The nanoparticles produced by the green chemistry approach would enhance the safety profile by avoiding synthetic agents and solvents in its preparations. This review encompasses toxicity consideration of nanoparticles, green synthesis techniques of nanoparticle preparation, biomedical application of nanoparticles, and future prospects.

Optimization and Characterization of Brimonidine Tartrate Nanoparticles-loaded In Situ Gel for the Treatment of Glaucoma.

Purposes: The present study aimed to develop brimonidine tartrate loaded poly(lactic-co-glycolic acid) acid vitamin E-tocopheryl polyethylene glycol 1000 succinate (BRT-PLGA-TPGS) nanoparticles in thermosensitivein situ gel to improve mucoadhensive properties and drug holding capacity for the better management of glaucoma.Methods: Nanoparticles was optimized by means of Box-Behnken Design (BBD). The formulations were prepared using various concentration of PLGA (0.1-0.4% w/v) and TPGS (0.3-0.5% w/v). The analytical data of fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and transmission electron microscopy (TEM) depicted the drug excipients compatibility and confirmed the nanoparticles. Nanoparticles incorporated gel was evaluated for transcorneal permeability, gelation time, gelling temperature, and rheological studies. In addition, in vitro, transcorneal permeation drug release studies and intraocular pressure (IOP) for optimized gel was also performed. Biocompatibility of formulations was investigated in rabbit model.Results: The drug loaded nanoparticles exhibited 115.72 ± 4.18 nm, 0.190 ± 0.02, -11.80 ± 2.24 mV and 74.85 ± 6.54% of mean size, polydispersity index (PDI), zeta potential and entrapment efficiency (% EE), respectively. As compared to marketed eye drop, the sustained and continuous release BRT release from Poloxamer-based in situ gel was 85.31 ± 3.51% till 24 h. The transcorneal steady-state flux (136.32 µg cm-2 h-1) of optimized in situ gel was approximately 3.5 times higher than marketed formulation (38.60 µg cm-2 h-1) flux at 4 h. The optimized formulation produces 3 fold greater influences on percentage reduction of IOP (34.46 ± 4.21%) than the marketed formulation (12.24 ± 2.90%) till 8 h.Conclusion: The incorporation of optimized BRT-PLGA-TPGS nanoparticles into a thermosensitivein situ gel matrix to improve precorneal residence time without causing eye irritation and also serve the sustained release of BRT through cornea for effective management of glaucoma.

Cellular and physiological approaches to evaluate the chelating effect of Chlorella on metal ion stressed lymphocytes.

Chlorella is a green alga consumed as dietary food supplement in pulverized form. In addition to its high nutritional value, it is reported as an excellent detoxifying agent. The pulverized Chlorella is partially soluble in water and insoluble portion has been reported for removal of mercury, cadmium and radioactive strontium from body. Chlorella contains a variety of metal-binding functional groups such as carboxyl, amino, phosphoryl, hydroxyl and carbonyl groups, which has high affinity towards various metal ions. The present study was envisaged to evaluate the chelating effect of water soluble fraction of Chlorella powder (AqCH) on metal ions. Fura-2 fluorescence ratio (F340/F380) was measured by fluorescence spectrometer (FS) after the exposure of chloride salt of metals viz., strontium, cobalt, barium, cesium, thallium and mercury to lymphocytes. Pretreatment of AqCH (0.1-20 mg mL-1) was given to evaluate the attenuating effect on fura-2 fluorescence ratio induced by metal ions. The intracellular levels of these metal ions were analyzed by atomic absorption spectrophotometer (AAS) and fluorescence microscopy (FM). Pretreatment with AqCH significantly attenuated the metal induced fluorescence ratio in dose-dependent manner. The results of AAS and FM were found in coherence with fura-2 fluorescence ratio which emphasized that AqCH significantly prevented the metal ions internalization. The present study suggests AqCH chelates with these metal ions and prevents its interaction with cells thereby reducing the intracellular mobilization of Ca2+.

Optimization and characterization of rivastigmine nanolipid carrier loaded transdermal patches for the treatment of dementia.

The present study aimed to develop nanolipid carrier (NLC) loaded transdermal system of rivastigmine for bioavailability enhancement. NLC was optimized using Box-Behnken Design (BBD). Optimized formulation comprises oil (4% w/w), tween 80 (3% w/w) and span 80 (1.8% w/w) and was characterized. It was found that the formulation exhibit 134.60 ±â€¯15.10 nm, 0.286 ±â€¯0.041, -11.80 ±â€¯2.24 mV and 70.56 ±â€¯1.20% of mean size, polydispersity index (PDI), zeta potential and entrapment efficiency, respectively. In vitro release studies showed there was more sustained release of drug from NLC loaded transdermal patches in comparison to Exelon® patch. Skin irritation studies proved the non-irritant nature of developed NLC based transdermal patch. From pharmacokinetic studies it was observed that there was increased Cmax and AUC0-72 in plasma treated with NLC loaded transdermal patches as compared to conventional patch. These experimental results indicate that NLC based transdermal patch could be utilized as a potential carrier for enhancing bioavailability of rivastigmine for the better treatment and management of dementia.

Formulation, characterization and in vitro-in vivo evaluation of flurbiprofen-loaded nanostructured lipid carriers for transdermal delivery.

Flurbiprofen is used in the treatment of arthritis. However, its multiple dosing due to short elimination half life is a concern for such treatment. This work aims to develop nanostructured lipid carriers (NLCs) of flurbiprofen and evaluate their potential for transdermal delivery. The NLCs were prepared by the optimized o/w emulsification-homogenization-sonication technique using coconut oil (liquid lipid). The NLCs were found to be spherical with uniform size (214 nm). The entrapment efficiency and zeta potential were 92.58% and -30.70 mV, respectively. Differential scanning calorimetry (DSC) showed the amorphous state of flurbiprofen encapsulated in NLCs. The percentage cumulative drug release through the excised rat skin from NLCs was biphasic and significantly prolonged compared with the commercial gel. DSC of the treated skin indicated that the NLCs penetrate into follicles of the skin and accumulate in the dermis. The bioavailability of flurbiprofen from NLCs was more than 1.7-fold that of the commercial gel. The NLCs showed a quick onset and sustained anti-inflammatory effect over period of 24 h for carrageenan-induced rat paw edema than the commercial gel. The stability data revealed that the NLCs were more stable when stored at 5°C. In conclusion, prepared NLCs have potential for skin targeting and sustained drug release.

Formulation and evaluation of flurbiprofen-loaded genipin cross-linked gelatin microspheres for intra-articular delivery.

Oral and parenteral formulations are challenging to produce therapeutic concentration of flurbiprofen in the joints. This encourages for the development of formulation for long term drug retention in the joint through intra-articular (i. a.) administration. In this study, genipin cross-linked gelatin microspheres of flurbiprofen were prepared for i. a. delivery. The microspheres were prepared using emulsification-homogenization-cross-linking method by changing the experimental variables such as concentration of cross-linker, cross-linking time and cross-linking temperature. The microspheres showed drug entrapment up to 76.19% with a mean particle size range of 5.91-8.19 µm. The degree of cross-linking and water-soluble fraction were 8.27-59.33% and 12.29-81.23%, respectively. SEM confirmed smooth surface and spherical shape of the microspheres. FTIR and (13)C-NMR confirmed cross-linking of gelatin by genipin. No chemical change in encapsulated drug was observed by FTIR and TGA. DSC and XRD indicated the molecular dispersion of drug within microspheres. Optimized microspheres could prolong the drug release for more than 108 h with anomalous transport. Histopathology confirmed the biocompatibility of microspheres in the rat (Wistar) knee joint. After 96 h of i. a. injection, significant higher amount (42.56%) of administered drug in cross-linked microspheres was recovered than uncross-linked microspheres (8.27%) confirming better drug retention efficiency (p < 0.01).

Intra-articular delivery of genipin cross-linked chitosan microspheres of flurbiprofen: preparation, characterization, in vitro and in vivo studies.

In this study, genipin cross-linked chitosan microspheres of flurbiprofen for intra-articular (i.a.) delivery were prepared. Emulsion-cross-linking method was used to prepare the microspheres using different concentrations of genipin and drug-to-polymer ratios. The mean particle size was found to be in the range of 5.18-9.74 µm with good % drug entrapment up to 80.97%. SEM indicated the spherical shape with smooth surface of drug-loaded cross-linked microspheres. FTIR confirmed cross-linking of genipin with chitosan and the absence of chemical interactions between drug, polymer, and cross-linker, which was further confirmed by TGA showing unaltered melting point of entrapped drug. DSC and XRD revealed the molecular dispersion of drug within microspheres. The optimized microspheres were able to release the drug for more than 108 h. The biocompatibility of the microspheres in the rat (Sprague-Dawley) knee joints was confirmed by histopathology. The results of pharmacokinetic study, decreased K(a) and T(max), lower C(max) and AUC((0-24)) and delayed MRT, suggested the significant extended release of flurbiprofen from microspheres in comparison with its solution at P<0.05. The recovery of flurbiprofen as the percent of administered dose followed by 24h after i.a. injection of microspheres was found to be 8.7 folds higher than its solution.