Exploring the potential of nanomedicine for gene therapy across the physicochemical and cellular barriers.

After COVID-19, a turning point in the way of pharmaceutical technology is gene therapy with beneficial potential to start a new medical era. However, commercialization of such pharmaceuticals would never be possible without the help of nanotechnology. Nanomedicine can fulfill the growing needs linked to safety, efficiency, and site-specific targeted delivery of Gene therapy-based pharmaceuticals. This review's goal is to investigate how nanomedicine may be used to transfer nucleic acids by getting beyond cellular and physicochemical barriers. Firstly, we provide a full description of types of gene therapy, their mechanism, translation, transcription, expression, type, and details of diseases with possible mechanisms that can only be treated with genes-based pharmaceuticals. Additionally, we also reviewed different types of physicochemical barriers, physiological and cellular barriers in nucleic acids (DNA/RNA) based drug delivery. Finally, we highlight the need and importance of cationic lipid-based nanomedicine/nanocarriers in gene-linked drug delivery and how nanotechnology can help to overcome the above-discussed barrier in gene therapy and their biomedical applications.

Mentha aquatica (Water Mint) as a Source of Active Pharmaceutical and Cosmetic Ingredients: A Critical Review.

Mentha aquatica L., or water mint, is an important member of the Mentha genus, and has long been used in traditional medicine, mainly to treat respiratory diseases such as the common cold. Nevertheless, although over the years many studies have shown that it's potential grows beyond this use, a review that highlights M. aquatica L.'s true potential is still lacking. Thus, the main purpose of the present article is to provide a thorough and multidisciplinary critical review of M. aquatica L., including its phytochemical characterization, main bioactivities, and current marketed cosmetic products. Many compounds have been identified as part of M. aquatica L. composition, such as terpenes, phenolic acids, phenols, and terpenoids, which have been linked to a vast therapeutic potential, namely anti-inflammatory, antioxidant, antibacterial, antifungal, antiobesity, and hepatoprotection bioactivities, with additional anticancer potential for several types of tumors (breast, lung, and skin), and psycho and neuroactive potential in depression, or Alzheimer's or Parkinson's disease. Additionally, it has been proven to be suitable for cosmetic application since several cleansing, hydrating, protecting, and/or odor masking products containing it are already available, with the main functions attributed to M. aquatica including refreshing/cooling effects, calming/soothing/relaxing effects, and purifying effects, properties closely related to its anti-inflammatory and antioxidant bioactivities. Hence, M. aquatica is an extremely versatile plant, with its extracts and essential oils having great therapeutic and cosmetic potential. With many marketed cosmetic products, future studies should focus on this plant's medicinal aspects, so that 1 day it can be part of therapeutic regimens.

A comprehensive review on transethosomes as a novel vesicular approach for drug delivery through transdermal route.

Drug delivery through transdermal route is one of the effective methods for the application of drugs. It overcomes many drawbacks which are encountered with the oral route. Moreover, many drugs are not able to pass through the stratum corneum, which is the main barrier for the transdermal drug delivery. Formation of ultra-deformable vesicles (UDVs) is a novel technique for the transdermal applications of the drugs. Transethosomes (TEs), ethosomes, and transferosomes are all part of the UDV. Because of the presence of increased concentrations of ethanol, phospholipids, and edge activators, TEs provide improved drug permeation through the stratum corneum. Because of the elasticity of TEs, drug penetration into the deeper layer of skin also increases. TEs can be prepared using a variety of techniques, including the cold method, hot method, thin film hydration method, and the ethanol injection method. It increases patient adherence and compliance because it is a non-invasive procedure of administering drugs. Characterization of the TEs includes pH determination, size and shape, zeta potential, particle size determination, transition temperature, drug content, vesicle stability, and skin permeation studies. These vesicular systems can be utilized to deliver a variety of medications transdermally, including analgesics, antibiotics, antivirals, and anticancer and arthritis medications. This review aims to describe vesicular approaches that had been used to overcome the barrier for the transdermal delivery of drug and also describes brief composition, method of preparation, characterization tests, mechanism of penetration of TEs, as well as highlighted various applications of TEs in medicine.

Ethosomes: a potential nanovesicular carrier to enhancing the drug delivery against skin barriers.

Ethosomes, which are liposomes like structures, mainly composed primarily of ethanol, have attracted considerable attention due to their potential to enhance the drug permeation via skin. The article discusses the formulation and preparation methods of ethosomes, offering insights into the various factors that influence their size, shape, and stability. Moreover, it explores the techniques used to assess the physicochemical properties of ethosomes and their impact on drug delivery effectiveness. The article also elucidates the mechanism by which ethosomes enhance skin permeation, emphasising their ability to modify the lipid structure and fluidity of the stratum corneum. Additionally, the review investigates the applications of ethosomes in diverse drug delivery scenarios, including the delivery of small molecules, peptides, and phytoconstituents. It highlights the potential of ethosomes to improve drug bioavailability, extend drug release, and achieve targeted delivery to specific skin layers or underlying tissues.

A comprehensive review on lipid-based nanoparticles via nose to brain targeting as a novel approach.

The central nervous system (CNS) has been a chief concern for millions of people worldwide, and many therapeutic medications are unable to penetrate the blood-brain barrier. Advancements in nanotechnology have enabled safe, effective, and precise delivery of medications towards specific brain regions by utilising a nose-to-brain targeting route. This method reduces adverse effects, increases medication bioavailability, and facilitates mucociliary clearance while promoting accumulation of drug in the targeted brain region. Recent developments in lipid-based nanoparticles, for instance solid lipid nanoparticles (SLNs), liposomes, nanoemulsions, and nano-structured lipid carriers have been explored. SLNs are currently the most promising drug carrier system because of their capability of transporting drugs across the blood-brain barrier at the intended brain site. This approach offers higher efficacy, controlled drug delivery, target specificity, longer circulation time, and a reduction in toxicity through a biomimetic mechanism.

Liposomes like advanced drug carriers: from fundamentals to pharmaceutical applications.

AIMS: There are around 24 distinct lipid vesicles described in the literature that are similar to vesicular systems such as liposomes. Liposome-like structures are formed by combining certain amphiphilic lipids with a suitable stabiliser. Since their discovery and classification, self-assembled liposome-like structures as active drug delivery vehicles captured researchers' curiosity. METHODOLOGY: This comprehensive study included an in-depth literature search using electronic databases such as PubMed, ScienceDirect and Google Scholar, focusing on studies on liposome and liposomes like structure, discussed in literature till 2024, their sizes, benefits, drawback, method of preparation, characterisation and pharmaceutical applications. RESULTS: Pharmacosomes, cubosomes, ethosomes, transethosomes, and genosomes, all liposome-like structures, have the most potential due to their smaller size with high loading capacity, ease of absorption, and ability to treat inflammatory illnesses. Genosomes are futuristic because of its affinity for DNA/gene transport, which is an area of focus in today's treatments. CONCLUSION: This review will critically analyse the composition, preparation procedures, drug encapsulating technologies, drug loading, release mechanism, and related applications of all liposome-like structures, highlighting their potential benefits with enhanced efficacy over each other and over traditional carriers by paving the way for exploring novel drug delivery systems in the Pharma industry.

A Comprehensive Review of Hydrogel-Based Drug Delivery Systems: Classification, Properties, Recent Trends, and Applications.

As adaptable biomaterials, hydrogels have shown great promise in several industries, which include the delivery of drugs, engineering of tissues, biosensing, and regenerative medicine. These hydrophilic polymer three-dimensional networks have special qualities like increased content of water, soft, flexible nature, as well as biocompatibility, which makes it excellent candidates for simulating the extracellular matrix and promoting cell development and tissue regeneration. With an emphasis on their design concepts, synthesis processes, and characterization procedures, this review paper offers a thorough overview of hydrogels. It covers the various hydrogel material types, such as natural polymers, synthetic polymers, and hybrid hydrogels, as well as their unique characteristics and uses. The improvements in hydrogel-based platforms for controlled drug delivery are examined. It also looks at recent advances in bioprinting methods that use hydrogels to create intricate tissue constructions with exquisite spatial control. The performance of hydrogels is explored through several variables, including mechanical properties, degradation behaviour, and biological interactions, with a focus on the significance of customizing hydrogel qualities for particular applications. This review paper also offers insights into future directions in hydrogel research, including those that promise to advance the discipline, such as stimuli-responsive hydrogels, self-healing hydrogels, and bioactive hydrogels. Generally, the objective of this review paper is to provide readers with a detailed grasp of hydrogels and all of their potential uses, making it an invaluable tool for scientists and researchers studying biomaterials and tissue engineering.

Mimosa pudica mucilage nanoparticles of losartan potassium: Characterization and pharmacodynamics evaluation.

The current research was to develop nanoparticles based on Mimosa pudica mucilage (MPM) that could encapsulate losartan potassium (LP). Nanoparticles (NPs) produced through ionic-gelation method; the polymerization of the mucilage carried out using calcium chloride as cross-linking agent. The MPMLP-NPs demonstrated vastly enhanced pharmaceutical characteristics, presented discrete surface with spherical shape of 198.4-264.6 nm with PDI ranging 0.326-0.461 and entrapment efficiency was in the range of 80.65 ± 0.82-90.79 ± 0.96%. FTIR and DSC indicated the stability of drug during the formulation of nanoparticles. An acute oral toxicity investigation found no significant alterations in behavior and histopathology criteria. The MPMLP-NPs formulation revealed the better rates and sustained effect as assessed with the commercial product. Moreover, low dose of MPMLP-NPs showed similar anti-hypertensive effect as assessed with the marketed tablet.

RIPK1 in Liver Parenchymal Cells Limits Murine Hepatitis during Acute CCl4-Induced Liver Injury.

Some life-threatening acute hepatitis originates from drug-induced liver injury (DILI). Carbon tetrachloride (CCl4)-induced acute liver injury in mice is the widely used model of choice to study acute DILI, which pathogenesis involves a complex interplay of oxidative stress, necrosis, and apoptosis. Since the receptor interacting protein kinase-1 (RIPK1) is able to direct cell fate towards survival or death, it may potentially affect the pathological process of xenobiotic-induced liver damage. Two different mouse lines, either deficient for Ripk1 specifically in liver parenchymal cells (Ripk1LPC-KO) or for the kinase activity of RIPK1 (Ripk1K45A, kinase dead), plus their respective wild-type littermates (Ripk1fl/fl, Ripk1wt/wt), were exposed to single toxic doses of CCl4. This exposure led in similar injury in Ripk1K45A mice and their littermate controls. However, Ripk1LPC-KO mice developed more severe symptoms with massive hepatocyte apoptosis as compared to their littermate controls. A pretreatment with a TNF-α receptor decoy exacerbated liver apoptosis in both Ripk1fl/fl and Ripk1LPC-KO mice. Besides, a FasL antagonist promoted hepatocyte apoptosis in Ripk1fl/fl mice but reduced it in Ripk1LPC-KO mice. Thus, the scaffolding properties of RIPK1 protect hepatocytes from apoptosis during CCl4 intoxication. TNF-α and FasL emerged as factors promoting hepatocyte survival. These protective effects appeared to be independent of RIPK1, at least in part, for TNF-α, but dependent on RIPK1 for FasL. These new data complete the deciphering of the molecular mechanisms involved in DILI in the context of research on their prevention or cure.

pH Responsive Abelmoschus esculentus Mucilage and Administration of Methotrexate: In-Vitro Antitumor and In-Vivo Toxicity Evaluation.

The rapid progression in biomaterial nanotechnology apprehends the potential of non-toxic and potent polysaccharide delivery modules to overcome oral chemotherapeutic challenges. The present study is aimed to design, fabricate and characterize polysaccharide nanoparticles for methotrexate (MTX) delivery. The nanoparticles (NPs) were prepared by Abelmoschus esculentus mucilage (AEM) and chitosan (CS) by the modified coacervation method, followed by ultra-sonification. The NPs showed much better pharmaceutical properties with a spherical shape and smooth surface of 213.4-254.2 nm with PDI ranging between 0.279-0.485 size with entrapment efficiency varying from 42.08 ± 1.2 to 72.23 ± 2.0. The results revealed NPs to possess positive zeta potential and a low polydispersity index (PDI). The in-vitro drug release showed a sustained release of the drug up to 32 h with pH-dependence. Blank AEM -CS NPs showed no in-vivo toxicity for a time duration of 14 days, accompanied by high cytotoxic effects of optimized MTX loaded NPs against MCF-7 and MD-MBA231 cells by MTT assay. In conclusion, the findings advocated the therapeutic potential of AEM/CS NPs as an efficacious tool, offering a new perspective for pH-responsive routing of anticancer drugs with tumor cells as a target.

COLOCASIA ESCULENTA CORMS MUCILAGE-ALGINATE MICROSPHERES OF OXCARBAZEPINE: DESIGN, OPTIMIZATION AND EVALUATION.

The present investigation was undertaken with an objective of formulating sustained release microspheres of oxcarbazepine (OXC), an anti-epileptic drug, to overcome poor patient compliance and exposure to high doses associated with currently marketed OXC dosage forms. Ionic gelation technique was used to prepare OXC microspheres by using sodium alginate along with rate controlling polymer Colocasia esculenta mucilage (CEM) matrix as well coated form. The microspheres have been characterized by differential scanning calorimetry (DSC) for understanding thermal stability and Fourier transform infrared (FT-IR) spectroscopy to investigate the chemical interaction as well as to assess the structure of drug-loaded formulation. Surface morphology of the microspheres was investigated by scanning electron microscope (SEM). The size distribution of OXC microspheres as studied by optical microscopy was in the range of 394-575 pm. The microspheres exhibited encapsulating efficiency from 75 to 92%. The release of drug from the microspheres at pH 1.2 is negligible. Under neutral conditions, the microspheres were swell and release was attributed mainly to polymer relaxation. The release pattern from microspheres followed Korsmeyer-Peppas model and the value of n > 1 showed that drug released by anomalous (non-Fickian) diffusion. The data obtained thus suggest that a microparticulate system can be successfully designed by using CEM with alginate for sustained delivery of OXC.

Nanoparticle-based Gene Therapy for Neurodegenerative Disorders.

Neurological disorders present a formidable challenge in modern medicine due to the intricate obstacles set for the brain and the multipart nature of genetic interventions. This review article delves into the promising realm of nanoparticle-based gene therapy as an innovative approach to addressing the intricacies of neurological disorders. Nanoparticles (NPs) provide a multipurpose podium for the conveyance of therapeutic genes, offering unique properties such as precise targeting, enhanced stability, and the potential to bypass blood-brain barrier (BBB) restrictions. This comprehensive exploration reviews the current state of nanoparticle-mediated gene therapy in neurological disorders, highlighting recent advancements and breakthroughs. The discussion encompasses the synthesis of nanoparticles from various materials and their conjugation to therapeutic genes, emphasizing the flexibility in design that contributes to specific tissue targeting. The abstract also addresses the low immunogenicity of these nanoparticles and their stability in circulation, critical factors for successful gene delivery. While the potential of NP-based gene therapy for neurological disorders is vast, challenges and gaps in knowledge persist. The lack of extensive clinical trials leaves questions about safety and potential side effects unanswered. Therefore, this abstract emphasizes the need for further research to validate the therapeutic applications of NP-mediated gene therapy and to address nanosafety concerns. In conclusion, nanoparticle-based gene therapy emerges as a promising avenue in the pursuit of effective treatments for neurological disorders. This abstract advocates for continued research efforts to bridge existing knowledge gaps, unlocking the full potential of this innovative approach and paving the way for transformative solutions in the realm of neurological health.

Comprehensive insights on treatment modalities with conventional and herbal drugs for the treatment of duodenal ulcers.

Areas of the body accessible to gastric secretions, such as the stomach and duodenum, are most commonly damaged by circumscribed lesions of the upper gastrointestinal tract mucosa. Peptic ulcer disease is the term for this illness (PUD). About 80% of peptic ulcers are duodenal ulcers, with stomach ulcers accounting for the remaining 20%. Duodenal ulcers are linked to the two primary results about Helicobacter pylori infection and COX inhibitor users. Additional causes might include drinking, smoking, stress, and coffee consumption. The indications and symptoms of a duodenal ulcer depend on the patient's age and the lesion's location. For duodenal ulcers, proton pump inhibitors (PPIs) are the usual course of treatment. This comprehensive study included an in-depth literature search in the literature and methods section using electronic databases such as PubMed, ScienceDirect, and Google Scholar. The search method included publications published from the inception of the relevant database to the present. Inclusion criteria included studies investigating different treatment options for duodenal ulcer disease, including traditional pharmacotherapy and naturopathic treatments. Data mining includes information on treatment techniques, treatment outcomes, and possible synergies between conventional and herbal treatments. In addition, this review critically examines the available information on the effectiveness, safety, and possible side effects of different treatments. The inclusion of conventional and herbal treatments is intended to provide a comprehensive overview of the many treatment options available for duodenal ulcer disease. A more comprehensive and personalized treatment plan can be achieved by incorporating dietary changes, lifestyle modifications, and, if necessary, herbal therapies to complement other treatments normally.

Chitin: A versatile biopolymer-based functional therapy for cartilage regeneration.

Chitin is the second most abundant biopolymer and its inherent biological characteristics make it ideal to use for tissue engineering. For many decades, its properties like non-toxicity, abundant availability, ease of modification, biodegradability, biocompatibility, and anti-microbial activity have made chitin an ideal biopolymer for drug delivery. Research studies have also shown many potential benefits of chitin in the formulation of functional therapy for cartilage regeneration. Chitin and its derivatives can be processed into 2D/3D scaffolds, hydrogels, films, exosomes, and nano-fibers, which make it a versatile and functional biopolymer in tissue engineering. Chitin is a biomimetic polymer that provides targeted delivery of mesenchymal stem cells, especially of chondrocytes at the injected donor sites to accelerate regeneration by enhancing cell proliferation and differentiation. Due to this property, chitin is considered an interesting polymer that has a high potential to provide targeted therapy in the regeneration of cartilage. Our paper presents an overview of the method of extraction, structure, properties, and functional role of this versatile biopolymer in tissue engineering, especially cartilage regeneration.

Bacterial tyrosinases and their inhibitors.

Bacterial tyrosinase is a copper-containing metalloenzyme with diverse physio-chemical properties, that have been identified in various bacterial strains, including actinobacteria and proteobacteria. Tyrosinases are responsible for the rate-limiting catalytic steps in melanin biosynthesis and enzymatic browning. The physiological role of bacterial tyrosinases in melanin biosynthesis has been harnessed for the production of coloring and dyeing agents. Additionally, bacterial tyrosinases have the capability of cross-linking activity, demonstrated material functionalization applications, and applications in food processing with varying substrate specificities and stability features. These characteristics make bacterial tyrosinases a valuable alternative to well-studied mushroom tyrosinases. The key feature of substrate specificity of bacterial tyrosinase has been exploited to engineer biosensors that have the ability to detect the minimal amount of different phenolic compounds. Today, the world is facing the challenge of multi-drugs resistance in various diseases, especially antibiotic resistance, skin cancer, enzymatic browning of fruits and vegetables, and melanogenesis. To address these challenges, medicinal scientists are developing novel chemotherapeutic agents by inhibiting bacterial tyrosinases. To serve this purpose, heterocyclic compounds are of particular interest due to their vast spectrum of biological activities and their potential as effective tyrosinase inhibitors. In this chapter, a plethora of research explores applications of bacterial tyrosinases in different fields, such as the production of dyes and pigments, catalytic applications in organic synthesis, bioremediation, food and feed applications, biosensors, wool fiber coating and the rationalized synthesis, and structure-activity relationship of bacterial tyrosinase inhibitors.

An updated landscape on nanopharmaceutical delivery for mitigation of colon cancer.

Globally, colorectal cancer (CRC) continues to rank among the leading causes of cancer-related death. Systemic toxicity, multidrug resistance, and nonspecific targeting often pose challenges to conventional therapy for CRC. Because it is a complex disease with a complex genetic and environmental pathophysiology, advanced therapeutic strategies are needed. Nanotechnology presents a potential solution that may maximize therapeutic efficacy while minimizing negative effects by enabling personalized delivery of anticancer drugs. This review focuses on recent developments in colorectal drug delivery systems based on nanotechnology. Numerous nanomaterials, including liposomes, dendrimers, micelles, exosomes, and gold nanoparticles, are developed and used. Distinctive characteristics of mentioned nanocarriers are discussed along with strategies that can be employed for enhancing the delivery of drugs to colorectal cancer cells. The review also quotes the most relevant preclinical and clinical studies that show how these nanomaterials improve drug solubility, stability, and targeted delivery while overcoming the shortcomings of conventional therapies. Nanotechnology has made CRC treatment very efficient and advanced, which has opened up new possibilities for targeted drug delivery. Preclinical and clinical studies have also proved that the use of nano-formulations in colon-specific delivery systems have significant results, indicating potential for better patient outcomes. Future research can be done in order to overcome the hurdles regarding biocompatibility, expansion, and regulatory challenges. Large-scale clinical trials and nanomaterial formulation optimization should be the main goals of future research to confirm the efficacy and safety of these novel treatments.

Preparation and Evaluation of a Self-Emulsifying Drug Delivery System for Improving the Solubility and Permeability of Ticagrelor.

Ticagrelor (TCG) is a BCS class IV antiplatelet drug used to prevent platelet aggregation in patients with acute coronary syndrome, having poor solubility and permeability. The goal of this study was to develop a self-nanoemulsifying drug delivery system (SNEDDS) of TCG to improve its solubility and permeability. The excipients were selected based on the maximum solubility of TCG and observed by UV spectrophotometer. Different combinations of oil, surfactant, and co-surfactant (1:1, 2:1, and 3:1) were used to prepare TCG-SNEDDS formulations, and pseudo-ternary phase diagrams were plotted. The nanoemulsion region was observed. Clove oil (10-20%), Tween-80 (45-70%), and PEG-400 (20-45%) were used as an oil, surfactant, and co-surfactant, respectively. The selected formulations (F1, F2, F3, F4, F5, and F6) were analyzed for ζ potential, polydispersity index (PDI), ζ size, self-emulsification test, cloud point determination, thermodynamic studies, entrapment efficiency, Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), in vitro dissolution, ex vivo permeation, and pharmacodynamic study. The TCG-SNEDDS formulations exhibited ζ potential from -9.92 to -6.23 mV, a ζ average of 11.85-260.4 nm, and good PDI. The in vitro drug release in phosphate buffer pH 6.8 from selected TCG-SNEDDS F4 was about 98.45%, and F6 was about 97.86%, displaying improved dissolution of TCG in 0.1 N HCl and phosphate buffer pH 6.8, in comparison to 28.05% of pure TCG suspension after 12 h. While the in vitro drug release in 0.1 N HCl from F4 was about 62.03%, F6 was about 73.57%, which is higher than 10.35% of the pure TCG suspension. In ex vivo permeability studies, F4 also exhibited an improved apparent permeability of 2.7 × 10-6versus 0.6708 × 10-6 cm2/s of pure drug suspension. The pharmacodynamic study in rabbits demonstrated enhanced antiplatelet activity from TCG-SNEDDS F4 compared to that from pure TCG suspension. These outcomes imply that the TCG-SNEDDS may serve as an effective means of enhancing TCG's antiplatelet activity by improving the solubility and permeability of TCG.

Evaluation of Plant-Based Silver Nanoparticles for Antioxidant Activity and Promising Wound-Healing Applications.

The current research focuses on the green synthesis of silver nanoparticles (AgNPs) using a polar extract of taro corms and the evaluation of its antioxidant properties and wound-healing applications. Taro corm extract (100 mL) was treated with a 5 mM AgNO3 solution (100 mL) at room temperature for the formation of AgNPs, and a color change was observed. The surface plasmon resonance (SPR) peaks in their UV-visible spectra appeared at a range of 438-445 nm. Fourier transform infrared, scanning electron microscopy, energy-dispersive X-ray, dynamic light scattering, and X-ray diffraction were used for the characterization of the taro corms extract-mediated AgNPs (TCE-AgNPs). The synthesized AgNPs were crystalline and spherical, with an average size of 244.9-272.2 nm with a polydispersity index of 0.530 and zeta potential of -18.8 mV, respectively. The antibacterial potential of TCE-AgNPs was tested, and the inhibition zones detected against Cronobacter sakazakii, Pseudomonas aeruginosa, Listeria monocytogenes, and Enterococcus faecalis were 28, 26, 18, and 13 mm, respectively. Furthermore, the antioxidant activity of TCE-AgNPs showed significant radical-scavenging activity compared to the standard used. Collagen content data collected from regenerated tissue and higher collagen content indicated rapid wound healing compared to others, which was seen in a group treated with TCE-AgNP film bandages.

Formulation, Characterization, and Evaluation of ß-Cyclodextrin Functionalized Hypericin Loaded Nanocarriers.

St. John's wort in western Europe has been extensively utilized for the treatment of mild to moderate depression. Hypericin, a red pigment, is found to be responsible for its antidepressant activity. The aim of the current study was to prepare a nanoemulsion (O/W) of hypericin designed for immediate delivery of the drug to the brain for the treatment of depression. The nanoemulsion was prepared by means of a homogenization technique, and that was followed by its physicochemical evaluation. Tween-80, Span-80, ß-cyclodextrin, ethanol, and eucalyptus oil were utilized for the manufacturing of the nanoemulsion. Morphological studies have revealed globular structures of nanosize that were confirmed by the zeta analysis. The consistency of particles was revealed by the low polydispersity values. pH values of all formulations lay within the range of nasal pH. The viscosity of the prepared formulations was affected by the increase in concentrations of ß-cyclodextrin. After passing from the centrifugation and freeze-thaw studies, the prepared formulations showed good stability. Formulation F2 having a composition of oil phase (0.125 mL), aqueous phase (1.25 mL), and ß-cyclodextrin (8%) showed the best results out of all the formulations, and F2 had a pH of 5.7, 5.35 cP viscosity, 1.332 refractive index, 148.8 globule size, and -10.8 zeta potential. The mean percentage drug release and in vitro and ex vivo percentage drug permeations were observed to be 71.75, 76, and 75.07%, respectively. Meanwhile, formulation F2 showed the maximum drug release and permeation. In vivo behavior studies including the open field test, elevated plus maze test, and tail suspension test were conducted to see the antidepressant effect of hypericin along with comparison with a commercially available treatment. In conclusion, the prepared formulation shows good efficacy as an antidepressant and can be considered as a natural alternative over synthetic drugs.

Thermo-Responsive Sol-Gel-Based Nano-Carriers Containing Terbinafine HCl: Formulation, In Vitro and Ex Vivo Characterization, and Antifungal Activity.

The current research aims to create a sol-gel-based nanocarrier containing terbinafine formulated for transdermal delivery of the drug into the skin. Sol-gel-based nanocarriers were prepared via the cold method using poloxamer-188, poloxamer-407, and distilled water. The prepared formulation was examined for pH, gelation temperature, Fourier transform infrared spectrophotometer (FTIR) analysis, thermal stability analysis, X-ray diffraction (XRD), scanning electron microscopy (SEM), particle size analysis, zeta potential, and anti-microbial activity. The in-vitro drug release study of F1 was found to be 94%, which showed greater drug release as compared to F2 and F3. The pH of the formulation was found to be within the range applicable to the skin. The gelation temperature was detected at 28 °C. The SEM images of formulations have spotted various particles well-segregated from each other. Analysis of formulations showed a mean globule size diameter of 428 nm, zeta potential values of 0.04 mV, refractive index (1.329), and viscosity (5.94 cP). FTIR analysis confirmed various functional groups' presence in the prepared formulation. Thermal analysis has confirmed the stability of the drug within the prepared formulation. The growth of inhibition was found to be 79.2% in 60 min, which revealed that the prepared formulation has shown good permeation from the membrane. Hence, the sol-gel-based nanocarrier formulation of terbinafine was successfully developed and evaluated.