Polypharmacy in Psychiatry: An In-depth Examination of Drug-drug Interactions and Treatment Challenges.

Polypharmacy in psychiatry is an in-depth examination of drug-drug interactions and treatment challenges that explores the intricate landscape of psychiatric polypharmacy, a practice involving the prescription of multiple medications to individuals with mental health disorders. This review is based on the critical aspects of drug-drug interactions and the associated treatment challenges. Psychiatric polypharmacy is motivated by the complexity of mental health conditions, where monotherapy may be insufficient. While it offers potential benefits, the practice raises concerns related to drug interactions that can compromise safety and efficacy. The review delves into the prevalence and clinical indications for psychiatric polypharmacy, thoroughly analyzing drug interactions, treatment challenges, and strategies for mitigation. Real-world case studies illustrate the complexities and outcomes of managing complex medication regimens, while emerging trends in personalized medicine, advancements in psychopharmacology, multidisciplinary approaches, and digital health solutions offer a glimpse into the future of psychiatric polypharmacy. This examination underscores the importance of a patient-centered, evidence-based approach in optimizing psychiatric polypharmacy to achieve therapeutic benefits while minimizing risks.

Healing the diabetic wound: Unlocking the secrets of genes and pathways.

Diabetic wounds (DWs) are open sores that can occur anywhere on a diabetic patient's body. They are often complicated by infections, hypoxia, oxidative stress, hyperglycemia, and reduced growth factors and nucleic acids. The healing process involves four phases: homeostasis, inflammation, proliferation, and remodeling, regulated by various cellular and molecular events. Numerous genes and signaling pathways such as VEGF, TGF-ß, NF-κB, PPAR-γ, MMPs, IGF, FGF, PDGF, EGF, NOX, TLR, JAK-STAT, PI3K-Akt, MAPK, ERK, JNK, p38, Wnt/ß-catenin, Hedgehog, Notch, Hippo, FAK, Integrin, and Src pathways are involved in these events. These pathways and genes are often dysregulated in DWs leading to impaired healing. The present review sheds light on the pathogenesis, healing process, signaling pathways, and genes involved in DW. Further, various therapeutic strategies that target these pathways and genes via nanotechnology are also discussed. Additionally, clinical trials on DW related to gene therapy are also covered in the present review.

A Comprehensive Guide to the Development, Evaluation, and Future Prospects of Self-nanoemulsifying Drug Delivery Systems for Poorly Water-soluble Drugs.

Self-Nano Emulsifying Drug Delivery Systems (SNEDDS) are novel formulations that can enhance the solubility and bioavailability of poorly water-soluble drugs. SNEDDS are composed of lipids, surfactants, co-solvents, and drugs and can spontaneously form nanoemulsions when mixed with water under mild agitation. SNEDDS can be formulated as liquid or solid dosage forms and can improve drug absorption by increasing the interfacial area, protecting the drug from degradation, and facilitating lymphatic transport. SNEDDS is characterized by various parameters such as particle size, zeta potential, droplet morphology, emulsification efficiency, drug solubility, and stability. SNEDDS offers several advantages over conventional dosage forms, such as dose reduction, faster onset of action, reduced variability, versatility, and ease of formulation. However, SNEDDS also face some limitations and challenges, such as drug precipitation, cost-effectiveness, compatibility with capsule shells, and lack of predictive in vitro models. SNEDDS has a promising future in the field of pharmaceuticals, especially for personalized medicine and targeted drug delivery.

CRISPR and Gene Editing: A Game-Changer in Drug Development.

CRISPR and gene editing technologies have emerged as transformative tools in medicine, offering unprecedented precision in targeting genetic disorders and revolutionizing drug development. This review explores the multifaceted impact of CRISPR across various medical domains, from hereditary diseases to infectious diseases and cancer. The potential of CRISPR in personalized medicine, therapeutic innovation, and pandemic prevention is highlighted, along with its role in reshaping traditional drug development processes. However, alongside its promise, ethical considerations loom large, particularly regarding germline editing and equitable access to treatments. The commercialization of CRISPR poses further challenges, raising questions about affordability and healthcare equity. Collaboration among scientists, policymakers, and the public is emphasized to navigate the ethical and societal implications of CRISPR responsibly. As the field advances, it is essential to ensure that the benefits of CRISPR are realized while addressing potential risks and maintaining a commitment to the well-being of future generations.

Innovative Strategies to Enhance mRNA Vaccine Delivery and Effectiveness: Mechanisms and Future Outlook.

The creation of mRNA vaccines has transformed the area of vaccination and allowed for the production of COVID-19 vaccines with previously unheard-of speed and effectiveness. The development of novel strategies to enhance the delivery and efficiency of mRNA vaccines has been motivated by the ongoing constraints of the present mRNA vaccine delivery systems. In this context, intriguing methods to get beyond these restrictions include lipid nanoparticles, self-amplifying RNA, electroporation, microneedles, and cell-targeted administration. These innovative methods could increase the effectiveness, safety, and use of mRNA vaccines, making them more efficient, effective, and broadly available. Additionally, mRNA technology may have numerous and far-reaching uses in the field of medicine, opening up fresh avenues for the diagnosis and treatment of disease. This paper gives an overview of the existing drawbacks of mRNA vaccine delivery techniques, the creative solutions created to address these drawbacks, and their prospective public health implications. The development of mRNA vaccines for illnesses other than infectious diseases and creating scalable and affordable manufacturing processes are some of the future directions for research in this area that are covered in this paper.

In Situ Photo Responsive Biodegradable Nanoparticle Forming Intrauterine Implant for Drug Delivery to Treat Ovarian Diseases: A Rationale-based Review.

BACKGROUND: Ovarian disease constitutes various types of endocrine disorders, such as polycystic ovarian syndrome (PCOS), ovarian cancer, premature ovarian failure, ovarian endometriosis, and ovarian cysts. The prevalence of ovarian-related diseases is highly vulnerable in the world. The utility of various drug delivery systems for ovarian diseases has resulted in varied success. Moreover, most of them lead to severe adverse effects and are incapable of ameliorating the signs and symptoms of the condition. HYPOTHESIS: Intrauterine devices (IUDs) have positioned themselves as a mechanism to deliver the drug for various ovarian-related diseases. Thereby avoiding various stability-related issues arising due to various physiological barriers of the female reproductive tract. However, the use of intrauterine devices for drug delivery to the ovaries has not been fully explored. This is attributed to the fact that they cause cysts in the ovaries and skepticism among patients and physicians. Photo-sensitive devices are an appealing approach for managing disorders affecting the ovaries. Photo-sensitive in situ forming intrauterine implants (IUIs) have several advantages, including simplicity in application, reduced invasiveness, as well as improved site-specific drug release control. Polymeric nanoparticles (PNPs) loaded with a drug may be a suitable choice to provide sustained release, alter the pharmacokinetics, and reduce the dose and dosing frequency. CONCLUSION: The current manuscript hypothesizes the utility of a PNP-loaded biodegradable photo-responsive intrauterine implantable device as an alternate novel strategy for ameliorating ovarian-related diseases.

Harnessing role of sesamol and its nanoformulations against neurodegenerative diseases.

Sesamol is a lignan of sesame seeds and a natural phenolic molecule that has emerged as a useful medical agent. Sesamol is a non-toxic phytoconstituent, which exerts certain valuable effects in the management of cancer, diabetes, cardiovascular diseases, neurodegenerative diseases (NDs), etc. Sesamol is known to depict its neuroprotective role by various mechanisms, such as metabolic regulators, action on oxidative stress, neuroinflammation, etc. However, its poor oral bioavailability, rapid excretion (as conjugates), and susceptibility to gastric irritation/toxicity (particularly in rats' forestomach) may restrict its effectiveness. To overcome the associated limitations, novel drug delivery system-based formulations of sesamol are emerging and being researched extensively. These can conjugate with sesamol and enhance the bioavailability and solubility of free sesamol, along with delivery at the target site. In this review, we have summarized various research works highlighting the role of sesamol on various NDs, including Alzheimer's disease, Huntington's disease, Amyotrophic lateral sclerosis, and Parkinson's disease. Moreover, the formulation strategies and neuroprotective role of sesamol-based nano-formulations have also been discussed.

Interplay of Gut Microbiota in Polycystic Ovarian Syndrome: Role of Gut Microbiota, Mechanistic Pathways and Potential Treatment Strategies.

Polycystic Ovarian Syndrome (PCOS) comprises a set of symptoms that pose significant risk factors for various diseases, including type 2 diabetes, cardiovascular disease, and cancer. Effective and safe methods to treat all the pathological symptoms of PCOS are not available. The gut microbiota has been shown to play an essential role in PCOS incidence and progression. Many dietary plants, prebiotics, and probiotics have been reported to ameliorate PCOS. Gut microbiota shows its effects in PCOS via a number of mechanistic pathways including maintenance of homeostasis, regulation of lipid and blood glucose levels. The effect of gut microbiota on PCOS has been widely reported in animal models but there are only a few reports of human studies. Increasing the diversity of gut microbiota, and up-regulating PCOS ameliorating gut microbiota are some of the ways through which prebiotics, probiotics, and polyphenols work. We present a comprehensive review on polyphenols from natural origin, probiotics, and fecal microbiota therapy that may be used to treat PCOS by modifying the gut microbiota.

A shift in the mechanisms controlling hippocampal engram formation during brain maturation.

The ability to form precise, episodic memories develops with age, with young children only able to form gist-like memories that lack precision. The cellular and molecular events in the developing hippocampus that underlie the emergence of precise, episodic-like memory are unclear. In mice, the absence of a competitive neuronal engram allocation process in the immature hippocampus precluded the formation of sparse engrams and precise memories until the fourth postnatal week, when inhibitory circuits in the hippocampus mature. This age-dependent shift in precision of episodic-like memories involved the functional maturation of parvalbumin-expressing interneurons in subfield CA1 through assembly of extracellular perineuronal nets, which is necessary and sufficient for the onset of competitive neuronal allocation, sparse engram formation, and memory precision.

Quality by Design-based RP-HPLC Method for Estimation of Curcumin in Rat Plasma and Fecal Microbiota Extract-based Solid Self-nano Emulsifying Drug Delivery System.

BACKGROUND: Curcumin (CRM) is known to possess various therapeutic properties, such as anti-inflammatory and antidiabetic properties, and is, therefore, considered to be an effective therapeutic. OBJECTIVE: A sensitive method for the estimation of CRM in plasma, as well as fecal matter-based solid self-nano emulsifying drug delivery system (S-SNEDDS), has been reported for the first time. METHODS: A bioanalytical method was optimized using Box-Behnken Design having 13 runs and 3 responses. The optimized method was developed using methanol and water (70:30 v/v) with a flow rate of 1 mL/min. Quercetin was used as an internal standard. A specificity test was also performed for the developed CRM solid self-nano emulsifying drug delivery system. RESULTS: The retention time of CRM was found to be 14.18 minutes. The developed method was validated and found to be linear in the range of 50-250 ng/mL with an R2 of 0.999. Accuracy studies indicated that CRM had a percentage recovery of less than 105% and more than 95%, respectively. Precision studies were carried out for inter, intraday, and inter-analyst precision, and the %RSD was found to be less than 2%. The limit of detection (LOD) and limit of quantification (LOQ) were found to be 3.37 ng/mL and 10.23 ng/mL, respectively. Stability studies for shortterm, long term and freeze-thaw cycles showed a %RSD of less than 2%, indicating the stability of CRM in the plasma matrix. Moreover, the blank fecal microbiota extract slurry did not show any peak at the retention time of CRM in a CRM-loaded solid nanoemulsifying drug delivery system containing fecal microbiota extract indicating its specificity. CONCLUSION: Hence, the developed method can have clinical implications as it helps estimate CRM in blood samples and also provides a simple and sensitive method for the estimation of plant-based flavonoids along with fecal microbiota extract formulations.

Expanding Arsenal against Neurodegenerative Diseases Using Quercetin Based Nanoformulations: Breakthroughs and Bottlenecks.

Quercetin (Qu), a dietary flavonoid, is obtained from many fruits and vegetables such as coriander, broccoli, capers, asparagus, onion, figs, radish leaves, cranberry, walnuts, and citrus fruits. It has proven its role as a nutraceutical owing to numerous pharmacological effects against various diseases in preclinical studies. Despite these facts, Qu and its nanoparticles are less explored in clinical research as a nutraceutical. The present review covers various neuroprotective actions of Qu against various neurodegenerative diseases (NDs) such as Alzheimer's, Parkinson's, Huntington's, and Amyotrophic lateral sclerosis. A literature search was conducted to systematically review the various mechanistic pathways through which Qu elicits its neuroprotective actions and the challenges associated with raw Qu that compromise therapeutic efficacy. The nanoformulations developed to enhance Qu's therapeutic efficacy are also covered. Various ongoing/completed clinical trials related to Qu in treating various diseases, including NDs, are also tabulated. Despite these many successes, the exploration of research on Qu-loaded nanoformulations is limited mostly to preclinical studies, probably due to poor drug loading and stability of the formulation, time-consuming steps involved in the formulation, and their poor scale-up capacity. Hence, future efforts are required in this area to reach Qu nanoformulations to the clinical level.

Gut Dysbiosis and Diabetic Foot Ulcer: Role of Probiotics.

Diabetic foot ulcer (DFU) is a multifactorial disease and one of the complications of diabetes. The global burden of DFU in the health sector is increasing at a tremendous rate due to its cost management related to hospitalization, medical costs and foot amputation. Hence, to manage DFU/DWs, various attempts have been made, including treating wounds systematically/topically using synthetic drugs, herbal drugs, or tissue engineering based surgical dressings. However, less attention has been paid to the intrinsic factors that are also the leading cause of diabetes mellitus (DM) and its complications. One such factor is gut dysbiosis, which is one of the major causes of enhancing the counts of Gram-negative bacteria. These bacteria produce lipopolysaccharides, which are a major contributing factor toward insulin resistance and inflammation due to the generation of oxidative stress and immunopathy. These all lead to DM and DFU. Probiotics are the commercial form of beneficial gut microbes that are taken as nutraceuticals by people of all ages to improve gut immunity and prevent gut dysbiosis. However, the role of probiotics has been less explored in the management of DFU. Hence, the therapeutic potential of probiotics in managing DFU is fully described in the current review. This report covers the linkage between gut dysbiosis and DFU, sources of probiotics, the mechanisms of probiotics in DW healing, and the impact of probiotic supplementation in treating DFU. In addition, techniques for the stabilization of probiotics, market status, and patents related to probiotics have been also covered. The relevant data were gathered from PubMed, Scopus, Taylor and Francis, Science Direct, and Google Scholar. Our systematic review discusses the utilization of probiotic supplementation as a nutraceutical for the management of DFU.

Multivariate Data Analysis and Central Composite Design-Oriented Optimization of Solid Carriers for Formulation of Curcumin-Loaded Solid SNEDDS: Dissolution and Bioavailability Assessment.

The study was initiated with two major purposes: investigating the role of isomalt (GIQ9) as a pharmaceutical carrier for solid self-nanoemulsifying drug delivery systems (S-SNEDDSs) and improving the oral bioavailability of lipophilic curcumin (CUN). GIQ9 has never been explored for solidification of liquid lipid-based nanoparticles such as a liquid isotropic mixture of a SNEDDS containing oil, surfactant and co-surfactant. The suitability of GIQ9 as a carrier was assessed by calculating the loading factor, flow and micromeritic properties. The S-SNEDDSs were prepared by surface adsorption technique. The formulation variables were optimized using central composite design (CCD). The optimized S-SNEDDS was evaluated for differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), microscopy, dissolution and pharmacokinetic studies. The S-SNEDDS showed a particle size, zeta potential and PDI of 97 nm, -26.8 mV and 0.354, respectively. The results of DSC, XRD, FTIR and microscopic studies revealed that the isotropic mixture was adsorbed onto the solid carrier. The L-SNEDDS and S-SNEDDS showed no significant difference in drug release, indicating no change upon solidification. The optimized S-SNEDDS showed 5.1-fold and 61.7-fold enhancement in dissolution rate and oral bioavailability as compared to the naïve curcumin. The overall outcomes of the study indicated the suitability of GIQ9 as a solid carrier for SNEDDSs.

Novel Nanostructured Lipid Carriers Co-Loaded with Mesalamine and Curcumin: Formulation, Optimization and In Vitro Evaluation.

PURPOSE: The aim of current study is to formulate, optimize and characterize the developed formulation of Mesalamine-Curcumin Nanostructured Lipid Carriers (Mes-Cur NLCs). METHODS: It was formulated using high pressure homogenization followed by probe sonication and formulation variables were optimized using Central Composite Design. The particle size (PS), zeta potential (ZP), entrapment efficiency (EE), drug release, cytotoxicity on NIH 3T3 fibroblasts cells and HaCaT keratinocytes cells and efficacy on RAW264.7 cells for optimized formulation was determined. RESULTS: The PS, ZP and EE were found to be 85.26 nm, -23.7 ± 7.45 mV, 99.2 ± 2.62 % (Mes) and 84 ± 1.51 % (Cur), respectively. The good correlation between predicted and obtained value indicated suitability and reproducibility of experimental design. NLCs showed spherical shape as confirmed by TEM. In vitro drug release profile of prepared formulation showed that Mes exhibited 100 % release at 48 h, whereas Cur exhibited 82.23 ± 2.97% release at 120 h. Both the drugs exhibited sustained release upon incorporation into the NLCs. The absence of any significant cell death during MTT assay performed on NIH 3T3 fibroblasts cells and HaCaT keratinocytes cells indicated that NLCs' were safe for use. Furthermore, significant reduction in nitric oxide level during anti-inflammatory evaluation of formulation on RAW264.7 cells showed excellent potential for the formulation to treat inflammation. The formulation was found stable as no significant difference between the PS, ZP and EE of the fresh and aged NLCs was observed. CONCLUSION: The outcomes of study deciphered successful formulation of Mes-Cur NLCs.