A Comparative Mathematical Analysis of Drug Release from Lipid-Based Nanoparticles.

Mathematical modeling of drug release from drug delivery systems is crucial for understanding and optimizing formulations. This research provides a comparative mathematical analysis of drug release from lipid-based nanoparticles. Drug release profiles from various types of lipid nanoparticles, including liposomes, nanostructured lipid carriers (NLCs), solid lipid nanoparticles (SLNs), and nano/micro-emulsions (NEMs/MEMs), were extracted from the literature and used to assess the suitability of eight conventional mathematical release models. For each dataset, several metrics were calculated, including the coefficient of determination (R2), adjusted R2, the number of errors below certain thresholds (5%, 10%, 12%, and 20%), Akaike information criterion (AIC), regression sum square (RSS), regression mean square (RMS), residual sum of square (rSS), and residual mean square (rMS). The Korsmeyer-Peppas model ranked highest among the evaluated models, with the highest adjusted R2 values of 0.95 for NLCs and 0.93 for other liposomal drug delivery systems. The Weibull model ranked second, with adjusted R2 values of 0.92 for liposomal systems, 0.94 for SLNs, and 0.82 for NEMs/MEMs. Thus, these two models appear to be more effective in forecasting and characterizing the release of lipid nanoparticle drugs, potentially making them more suitable for upcoming research endeavors.

A review of the ethnomedicinal, phytochemical, and pharmacological properties of the Ferulago genus based on Structure-Activity Relationship (SAR) of coumarins.

BACKGROUND: The Ferluago W.D.J. Koch genus includes 48 accepted perennial herbs that are distributed in the Mediterranean region, Southeast Europe, Central and Middle East of Asia. These plants are widely used in folk and conventional medicine due to their biological benefits such as anti-microbial, anti-inflammatory, anti-cancer, and immunomodulatory properties. Conducting a comprehensive review based on the structure activity relationships (SARs) of the coumarins, which has not been previously documented, can lead to a better insight into the genus Ferulago and its beneficial therapeutic activities. METHODS: This review covers literature from 1969 to 2023, were collected from various scientific electronic databases to review phytochemical, pharmacological, and ethnopharmacological data of Ferulago species, as well as latest information on the SAR of reported coumarins from this genus. RESULTS: Phytochemical studies showed that the biological actions of this genus are mediated by the reported specialized metabolites, such as coumarins and flavonoids. Simple coumarins, prenylated coumarins, furanocoumarins, and pyranocoumarins are the largest subclasses of coumarins found in diverse Ferulago species, which have discussed the biological effects of them with a focus on the Structure-Activity Relationship (SAR). For example, prenylated coumarins have shown potential leishmanicidal and anti-neuropsychiatric effects when substituted with a prenyl group at the 7-hydroxy, as well as the C6 and C8 positions in their scaffold. Similarly, furanocoumarins exhibit varied biological activities such as anti-inflammatory, anti-proliferative, and anti-convulsant effects. Modifying substitutions at the C5 and C6 positions in furanocoumarins can enhance these activities. CONCLUSION: This study conducted a comprehensive review of all available information on the phytochemical and pharmacological characteristics of Ferulago species. Given the high occurrence of coumarins in this genus, which exhibit potential anti-Alzheimer and anti-microbial properties, it presents promising new therapeutic avenues for addressing these common issues. Further investigation is needed to understand the molecular-level mechanisms of action and to explore their clinical applications.

Hypersensitivity reaction to rivaroxaban with a successful switch to apixaban: A case report.

Key Clinical Message: The precise management of hypersensitivity reactions to direct oral anticoagulants (DOACs) and the potential for cross-reactivity among different DOACs remain unclear. In such cases, switching between DOACs may be feasible and could be considered, but close monitoring for adverse effects is essential, tailored to individual patient responses and tolerability. Abstract: Hypersensitivity reactions to DOACs, though considered rare, have been documented. This report describes the case of a 28-year-old male with a history of testicular cancer who was recently diagnosed with deep vein thrombosis. He was referred to an outpatient pharmacotherapy clinic due to suspected rivaroxaban-induced cutaneous reactions. Following a thorough evaluation, his anticoagulant therapy was switched from rivaroxaban to apixaban. This change was successfully implemented, and no hypersensitivity symptoms recurred during subsequent follow-up. This case demonstrates the importance of recognizing potential adverse reactions to DOACs and illustrates the feasibility of switching anticoagulants under close medical supervision to ensure patient safety and effective treatment.

Safety and efficacy of a polyherbal formulation from traditional Persian medicine in patients with calcium kidney stones: A randomized, double-blinded clinical trial.

Background: 10%-15% of the world's population suffers from kidney stones. Nearly 50% increase was observed in diagnosing and treating nephrolithiasis in the last decades. Effective medical treatment for the disease is not yet well established. Moreover, there is an increasing global demand to manage diseases using complementary and alternative medicine. This study aimed to formulate and assess the safety and efficacy of a multi-ingredient formulation from traditional Persian medicine (TPM) known as Mofatet powder in patients suffering from calcium kidney stones. Materials and Methods: The aqueous extract of Mofatet powder was prepared, freeze-dried, and formulated as capsules. 26 patients in the drug group and 25 patients in the placebo group used 500 mg capsules of the drug/placebo twice daily for 5 weeks. Ultrasonography/kidney, ureter and bladder imaging, urine analysis, and biochemical parameters were evaluated before and after the intervention. Results: The imaging results showed a 60.73% decrease (P < 0.001) in stone size in the drug group. Moreover, the urinary calcium decreased (P = 0.02) and the urinary magnesium increased (P < 0.001) in the drug group. No remarkable changes were observed in the placebo group in these parameters. No significant effect was observed in aspartate transaminase, alanine transaminase, serum creatinine, and blood urea nitrogen levels in none of the groups. Conclusion: This study suggests that Mofatet powder was effective in reducing calcium kidney stones size with no potential nephro/hepatotoxicity. After confirming these results in larger clinical trials with longer duration, this formulation can be considered a treatment for nephrolithiasis.

Successful management of severe generalized tetanus in a 23-year man with phenobarbital adjuvant: A case report.

Generalized tetanus is still a global concern with a mortality rate of up to 50%, especially in low and middle-income countries. We reported a 23-year-old man from Afghanistan admitted to emergency department, with the chief complaint of generalized severe spasms and lockjaw. The patient had skin lesions and had never been vaccinated against tetanus. He intubated and admitted to the intensive care unit (ICU) with diagnose of severe generalized tetanus. After receiving tetanus immunoglobulin and intravenous metronidazole, a combination therapy of midazolam, propofol, atracurium, and morphine was administered. Due to the refractory muscular spasms intravenous phenobarbital started and little by little recovery was achieved. The patient receiving the first two doses of the Td vaccine, and discharged on Day 42 of hospitalization with no symptom recurrence. This case management showed adding phenobarbital to severe tetanus treatment regimen could significantly reduce refractory spasm caused by tetanus, also decrease other medication requirement.

Trimethoprim/sulfamethoxazole desensitization in an HIV-positive patient with previous Stevens-Johnson syndrome; a failed study.

Drug-induced Stevens-Johnson syndrome (SJS) is a rare but life-threatening hypersensitivity reaction. Drug desensitization might be considered in drug-allergic patients with no therapeutic alternative. A 29-year-old man with a recent diagnosis of HIV and HBV (CD4 count: 4 cells/mm3) who has been receiving Trimethoprim/sulfamethoxazole (TMP/SMX) for Pneumocystis pneumonia (PCP) prophylaxis was admitted at Imam Khomeini hospital complex affiliated to Tehran University of Medical Sciences, with the diagnosis of SJS due to TMP/SMX. After 45 days of supportive care, the patient was a candidate for TMP/SMX desensitization due to our region's unavailability of alternative agents. A 9-day desensitization protocol was used, but the patient complained about diarrhea with severe pain in the rectal mucosa, and macules developed over his lips again on the third day. As a result, the desensitization process immediately stopped, and after the signs and symptoms were resolved, the patient was discharged with Clindamycin tablet 600 mg TDS. Unfortunately, two weeks after discharge, the patient experienced acute kidney injury (AKI) and expired after two dialysis sessions.

An Overview of Pharmacological and Clinical Aspects of Spirulina.

Spirulina or Arthrospira, a Cyanobacterium from the class Cyanophyceae, with a wide range of properties, has been applied for over 400 years. The present study aimed to review available investigations surrounding the clinical and pharmacological properties of Spirulina that have been carried out so far. Databases including Scopus, PubMed, Google Scholar, and Web of Science were searched for relevant literature using the keywords: (Spirulina), (pharmacology), and (clinical). About 130 papers that studied the pharmacological characteristics of Spirulina in animal models, as well as clinical trials, were selected from the beginning to 29 July 2021. According to this review, antioxidative, anti-inflammatory, anti-neoplastic, hypolipidemic, antiviral, immunomodulatory, antimicrobial, anti-atherogenic, anti-diabetic, and radio-protective functions are attributed to Spirulina. Moreover, Spirulina's positive influence on several organs, including hair, skin, liver, CNS, lung, and genitourinary tract, are ascribed to different components of various species of Spirulina such as Spirulina platensis, Spirulina fusiformis, and Spirulina maxima. Although so many studies have been accomplished on every aspect of Spirulina in recent years, the lack of a comprehensive investigation surrounding this microalga encouraged us to prepare this paper. Therefore, the present study could be considered an up-to-date overview of the clinical, pharmacological, and molecular aspects of Spirulina, resulting in more occupational research on this valuable organism.

Amplifying the Sensitivity of Polydiacetylene Sensors: The Dummy Molecule Approach.

There is an increasing need for fast and accurate assessment of various health conditions, where polydiacetylenes (PDA), having unique stress-sensitive optical properties, have great potential. When the conjugated backbone of PDA is disturbed by steric repulsion between the receptor-target complexes formed at the PDA surface via specific recognition events, the bandgap of PDA increases and produces color change and fluorescent emission as a dual sensory signal. However, this detection mechanism suggests an intrinsic sensitivity limit of PDA platform because unless adjacent receptors are occupied by target molecules no signal is anticipated. A novel approach to improve the sensitivity and limit of detection of PDA sensors has been developed by preoccupying the surface of PDA liposomes with an optimized amount of artificial target molecules named as dummy molecules. The sensitivity and limit of detection (LOD) showed large improvement by the surface-bound dummy molecules. In addition, the dummy strategy was synergically integrated with another sensitivity enhancing method with a different working mechanism in a PDA sensor for Neomycin detection. When optimized, the LOD of the PDA sensor was improved to 7 nM from 80 nM of the control and the signal intensity increased consistently throughout the entire tested concentration range of the target Neomycin. Finally, the general applicability of the dummy strategy to other target molecules was successfully confirmed by implementing the dummy strategy in a PDA sensor for Surfactin detection.

Heavy atom oriented orbital angular momentum manipulation in metal-free organic phosphors.

Metal-free purely organic phosphors (POPs) are emerging materials for display technologies, solid-state lighting, and chemical sensors. However, due to limitations in contemporary design strategies, the intrinsic spin-orbit coupling (SOC) efficiency of POPs remains low and their emission lifetime is pinned in the millisecond regime. Here, we present a design concept for POPs where the two main factors that control SOC-the heavy atom effect and orbital angular momentum-are tightly coupled to maximize SOC. This strategy is bolstered by novel natural-transition-orbital-based computational methods to visualize and quantify angular momentum descriptors for molecular design. To demonstrate the effectiveness of this strategy, prototype POPs were created having efficient room-temperature phosphorescence with lifetimes pushed below the millisecond regime, which were enabled by boosted SOC efficiencies beyond 102 cm-1 and achieved record-high efficiencies in POPs. Electronic structure analysis shows how discrete tuning of heavy atom effects and orbital angular momentum is possible within the proposed design strategy, leading to a strong degree of control over the resulting POP properties.

Cardiovascular implications of the COVID-19: Management of complications and drug safety concerns.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, has rapidly spread worldwide and has been infected more than 219 million individuals with 4.55 million deaths worldwide as of September 2021, causing a pandemic. Preexisting cardiovascular (CV) comorbidities such as hypertension, diabetes, and coronary artery disease seem to be associated with greater severity of infection, worse prognosis, and higher mortality. Moreover, COVID-19 can contribute to CV complications, including acute myocardial injury, arrhythmia, acute coronary syndrome, and venous thromboembolism, emphasizing the importance of precocious detection and implementation of optimal therapeutic strategies. This review provides an overview of evidence-based data of CV complications of COVID-19, focusing on their management strategies, as well as potential cardiac adverse effects and drug interactions, due to off-label and investigational drugs used for the treatment of COVID-19.

The role of halogen bonding in metal free phosphors.

The enhanced spin-orbit coupling necessary for phosphorescence is thought to be due to the halogen bonding that is present in the all-organic crystalline systems. To elucidate the underlying mechanism, the electronic and optical properties of purely organic phosphor candidates are investigated using density functional theory calculations. The unit cell structure of a known organic phosphor containing bromine is used to validate the accuracy of the computational methodology. Compared to experiments, the calculated lattice constants deviate by less than 1 percent for each lattice constant. The same computational approach is then used to predict the lattice constants for molecular analogs containing fluorine, chlorine, and iodine. Electronic structure and photonic properties of the predicted crystals are computed. Finally, the presence of halogen bonding is corroborated, with fluorine forming the weakest and iodine the strongest halogen bonding interactions. Our findings demonstrate how computational methods can be effectively used for the predictive design of organic materials in lighting devices.

Charge Transfer as the Key Parameter Affecting the Color Purity of Thermally Activated Delayed Fluorescence Emitters.

The key factors determining the emission bandwidth of thermally activated delayed fluorescence (TADF) are investigated by combining computational and experimental approaches. To achieve high internal quantum efficiencies in a metal-free organic light-emitting diode via TADF, the first triplet (T1) to first singlet (S1) reverse intersystem crossing is promoted by configuring molecules in an electron donor-acceptor (D-A) alternation with a large dihedral angle, which results in a small energy gap (ΔEST) between S1 and T1 levels. This allows for effective non-radiative up-conversion of triplet excitons to singlet excitons that fluoresce. However, this traditional molecular design of TADF results in broad emission spectral bands (full-width at half-maximum = 70-100 nm). Despite reports suggesting that suppressing the D-A dihedral rotation narrows the emission band, the origin of emission broadening remains elusive. Indeed, our results suggest that the intrinsic TADF emission bandwidth is primarily determined by the charge transfer character of the molecule, rather than its propensity for rotational motion, which offers a renewed perspective on the rational molecular design of organic emitters exhibiting sharp emission spectra.

Conjugated Copolymers That Shouldn't Be.

Multiple studies have explored using cage silsesquioxanes (SQs) as backbone elements in hybrid polymers motivated by their well-defined structures and physical and mechanical properties. As part of this general exploration, we report unexpected photophysical properties of copolymers derived from divinyl double decker (DD) SQs, [vinyl(Me)Si(O0.5 )2 ][PhSiO1.5 ]8 [(O0.5 )2 Si(Me)vinyl] (vinylDDvinyl). These copolymers exhibit strong emission red-shifts relative to model compounds, implying unconventional conjugation, despite vinyl(Me)Si(O-)2 siloxane bridges. In an effort to identify minimum SQ structures that do/do not offer extended conjugation, we explored Heck catalyzed co-polymerization of vinyl-ladder(LL)-vinyl compounds, vinyl(Me/Ph)Si(O0.5 )2 [PhSiO1.5 ]4 (O0.5 )2 Si(Me/Ph)vinyl, with Br-Ar-Br. Most surprising, the resulting oligomers show 30-60 nm emission red-shifts beyond those seen with vinylDDvinyl analogs despite lacking a true cage. Further evidence for unconventional conjugation includes apparent integer charge transfer (ICT) between LL-co-thiophene, bithiophene, and thienothiophene with 10 mol % F4 TCNQ, suggesting potential as p-type doped organic/inorganic semiconductors.

Traditional Aspects of Sciatic Pain Management and Allied Therapies from Persian Medical Reports.

Sciatica is a common back pain caused by irritation of the sciatic nerve. Current pharmacologic therapies have proven inadequate for many patients with sciatic pain. On the other hand, there is a globally increasing demand for the use and administration of natural medicaments for this disorder. Traditional Persian Medicine (TPM) is a school of medicine and a medicinal plant-based resource for clinical studies put forward by Persian scholars. The aim of the present study is to gather and study the effectiveness of all medicinal plants from five main Persian pharmacopeias. Furthermore, different databases such as PubMed and Scopus have been checked to derive relevant activities for these plants. In all, 99 medicinal plants related to 42 families have been authenticated. Asteraceae and Apiaceae were the most frequent families and roots and seeds were the most reported botanical parts. The employed routes of administration were oral (54%), topical (33%) and rectal (13%). Anti-inflammatory, analgesic activity and antinociceptive properties of medicines are known as some main mechanisms to manage sciatic pain. These functions are possessed by 30%, 15%, and 15% of the studied plants, respectively. Medicaments that can be introduced as lead agents for further investigation are Zingiber officinale Roscoe, Olea europaea L., Strychnos nux-vomica L and Artemisia vulgaris L which showed all of these properties in previous studies. Hence, conducting adducible clinical trials using these lead agents may lead to novel drugs with lesser undesirable and much more therapeutic effects on controlling sciatic pain.

Design principles for the energy level tuning in donor/acceptor conjugated polymers.

To identify reliable molecular design principles for energy level tuning in donor/acceptor conjugated polymers (CPs), we studied the governing factors by means of ab initio calculations based on density-functional theory (DFT). We investigated a series of CPs in which we independently and systematically varied the electron withdrawing power of the acceptor unit and the electron donating power of the donor unit, while maintaining the same conjugated chain conformation. We observed that the introduction of a stronger acceptor unit, while keeping the same donor unit in the CP, lowers the LUMO level, but leaves the HOMO level almost unchanged. Conversely, enhancing the strength of the donor unit for the same acceptor unit raises the HOMO level, while maintaining the LUMO level. We identified strong correlations between the frontier orbital energy levels and the degree of orbital localization, which depends on the electron donating or withdrawing power of the molecular groups carrying the orbitals. Moreover, the HOMO/LUMO gap of the CP is directly proportional to the charge transfer between donating and accepting units, which provides a robust design criterion for CPs.

Molecular Design Approach Managing Molecular Orbital Superposition for High Efficiency without Color Shift in Thermally Activated Delayed Fluorescent Organic Light-Emitting Diodes.

Molecular design principles of thermally activated delayed fluorescent (TADF) emitters having a high quantum efficiency and a color tuning capability was investigated by synthesizing three TADF emitters with donors at different positions of a benzonitrile acceptor. The position rendering a large overlap between the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) enhances the quantum efficiency of the TADF emitter. Regarding the orbital overlap, donor attachments at 2- and 6-positions of the benzonitrile were more beneficial than 3- and 5-substitutions. Moreover, an additional attachment of a weak donor at the 4-position further increased the quantum efficiency without decreasing the emission energy. Therefore, the molecular design strategy of substituting strong donors at the positions allowing a large molecular orbital overlap and an extra weak donor is a good approach to achieve both high quantum efficiency and a slightly increased emission energy.

A Review on Pharmacological and Clinical Aspects of Linum usitatissimum L.

INTRODUCTION AND BACKGROUND: Linum usitatissimum L., known as common Flax or linseed, from the family Linnaceae, has long been cultivated in different nations due to its applications in medicine and industry. The present study aims to collect nearly all available information about chemical constituents of Flax, as well as pharmacological properties and confirmed clinical usages of it. METHODS: We searched through databases such as Scopus and PubMed for relevant literature using the keywords: Linum usitatissimum, pharmacology and phytochemical from the beginning to 13 Aug 2017. Nearly 60 relevant papers, relating to a pharmacological and phytochemical constituent of L. usitatissimum were selected. RESULTS AND DISCUSSION: According to our researches, various properties were attributed to L. usitatisimum including antioxidant, immunomodulatory, anti-inflammatory, antimicrobial, antiprotozoal, insecticidal, analgesic, anti-hyperlipidemia, anti-hyperglycemic, anti-tumor, wound healing and Feticidal activities. There were also many reports on disease prevention and healing properties of the flax. Diseases like: GI disorders, cardiovascular, urogenital, respiratory diseases and some neurological syndromes were mentioned to be treated by Flax. The application of Flax in drug formulations was also investigated. CONCLUSION: Despite so much animal studies that have been accomplished, there have not been enough clinical trials done on pharmacological properties of L. usitatissimum. Therefore, this study could be considered as a concise and up to date overview for further facile studies and clinical trials over the valuable plant, L. usitatissimum.

A Review of Herbal Remedies for Multiple Sclerosis-Like Disorders in Traditional Persian Medicine (TPM).

BACKGROUND: Among various neurological disorders, multiple sclerosis (MS) is an expanding global immune- related inflammatory disease with complex etiologies. There is increasing demand for the use and administration of natural medicaments for this disorder. Traditional Persian Medicine (TPM) is a school of medicine and a medicinal plants-based resource for clinical studies put forward by Persian scholars. OBJECTIVE: This paper aims to gather and study the effectiveness of all medicinal plants from the most popular Persian pharmacopeias. Five main Persian pharmacopeias from the 9th to the 18th century A.D. have been studied to identify the remedial plants for this disorder. Moreover, PubMed, and Scopus databases have been checked to derive relevant activities for these plants. Khaddar (numbness), Esterkha (Palsy) and Falej (quadriplegia) are traditional definitions; these are clinically close to what is known as MS in today's medicine. CONCLUSION: In all, 118 medicinal plants, related to 65 families, have been authenticated out of 157 chosen medicaments. Apiaceae is the most frequent family (13 reports). Fruits and roots of plants have been the most reported botanical parts (34 and 32 items). The employed routes of administration are topical, oral, or a combination of the two (27, 57, and 34 sequentially). Fifteen medicines have been reported for Khaddar, Esterkha, and Falej simultaneously. Antioxidant activities, immunomodulatory, and anti-inflammatory properties of medicines are known as some main mechanisms to manage MS. These functions are possessed by 81%, 36%, and 48% of the studied plants, respectively. Hence, conducting adducible clinical trials and highly approved experimental tests on animals may lead to novel drugs with lesser undesirable and much more therapeutic effects on controlling MS.

Erratum: hyperhomocysteinemia and neurologic disorders: a review.

[This corrects the article on p. 281 in vol. 10, PMID: 25324876.].