In vitro Evaluation of Skin Related Enzyme Inhibitory Effect and Emulgel Formulation Development Studies of Onobrychis Argyrea subsp. Argyrea with Phytochemical Analysis.

Species of Onobrychis have been used to treat skin disorders such as wounds and cuts in folk medicine and Onobrychis argyrea subsp. argyrea (OA) commonly known as 'silvery sainfoin', is a member of this genus. In this study, it was aimed to investigate the skin-related biological activities and phytochemical characterization of OA. Moreover, an emulgel formulation was developed from the main methanolic extract of the plant (OAM). Initially, to identifiy of the active fractions, aerial parts of the plant material was extracted with methanol and fractionated by n-hexane, chloroform, ethyl acetate and n-butanol, respectively. Antioxidant activity was determined by CUPRAC, TOAC, FRAP and DPPH assays. Thereafter, the inhibition potential of OAM, novel formulation and all fractions was measured against elastase, collagenase, tyrosinase and hyaluronidase enzymes. OAM was analyzed and characterized by LC/MS-MS. The major bioactive flavonoids which are rutin and isoquercetin were measured and compared as qualitative and quantitative via high performance thin layer chromatography (HPTLC) analysis in OAM and fractions. The results showed that extracts of OA can be a potential cosmeceutical agent for skin related problems.

Novel Microemulsion Containing Benzocaine and Fusidic Acid Simultaneously: Formulation, Characterization, and In Vitro Evaluation for Wound Healing.

Modern drug carrier technologies, such as microemulsions with small droplet sizes and high surface areas, improve the ability of low water solubility active ingredients to permeate and localize. The goal of this study was to create microemulsion formulations for wound healing that contained both fusidic acid (FA), an antibacterial agent, and benzocaine (BNZ), a local anesthetic. Studies on characterization were carried out, including viscosity, droplet size, and zeta potential. The drug-loaded microemulsion had a stable structure with -3.014 ± 1.265 mV of zeta potential and 19.388 ± 0.480 nm of droplet size. In both in vitro release and ex vivo permeability studies, the microemulsion was compared with Fucidin cream and oily BNZ solution. According to the drug release studies, BNZ release from the microemulsion and the BNZ solution showed a similar profile (p > 0.05), while FA release from the microemulsion had a higher drug release compared to Fucidin cream (p < 0.001). The microemulsion presented lower drug permeation (p > 0.05) for both active ingredients, on the other hand, provided higher drug accumulation compared to the control preparations. Moreover, according to the results of in vitro wound healing activity, the microemulsion indicated a dose-dependent wound healing potential with the highest wound healing activity at the highest concentrations. To the best of our knowledge, this developed BNZ- and FA-loaded microemulsion would be a promising candidate to create new opportunities for wound healing thanks to present the active ingredients, which have low water solubility, in a single formulation and achieved higher accumulation than control preparations.

Preparation, characterization, and toxicity evaluation of microemulsion formulation containing prunetin for potential oral applications.

Phytochemicals as therapeutic alternatives can have a fundamental impact on the various stages of inflammation and its resolution. Prunetin is a naturally occurring isoflavone and has been claimed to have numerous therapeutic potentials. The objective of this study is preparation, characterization, and toxicity evaluation of microemulsion formulation containing prunetin (PMF) for potential oral applications. With this research, it was targeted to emphasize the way of improving the therapeutic efficacy of natural biomolecules with a nontoxic and effective formulation. In the study, the pseudo-ternary phase diagram was developed and PMF was characterized by conductivity, droplet size, viscosity and pH. Effects against to cytokines (IL-1ß and IL-6) and TNF-α levels of the PMF were determined by ELISA technique. Genotoxicity and acute oral toxicity tests were carried out according to OECD guidelines. The results showed that PMF is a colloid system that reduced proinflammatory cytokine levels in LPS-induced macrophage cells compared to the control group. PMF demonstrated no mutagenic activity against TA98, TA100, TA1535, and TA1537 Salmonella strains. The in vivo oral acute toxicity test results indicated that PMF did not show mortality or significant side effects even at 2000 mg/kg bw. This study represents PMF showed a good safety profile in animal study. It is thought that this formulation may have anti-inflammatory potential with further in vivo testing.

Enhancing Oral Bioavailability of Domperidone Maleate: Formulation, In-Vitro Permeability Evaluation, In-Caco-2 cell Monolayers and In-Situ Rat Intestinal Permeability Studies.

BACKGROUND: The domperidone maleate, a lipophilic agent classified as a Biopharmaceutical Classification System Class II substance with weak water solubility. Self- Emulsifying Drug Delivery System is a novel approach to improve water solubility and, ultimately bioavailability of drugs. OBJECTIVE: This study aimed to develop and characterize new domperidone-loaded self-emulsifying drug delivery systems as an alternative formulation and to evaluate the permeability of domperidone-loaded self-emulsifying drug delivery systems by using Caco-2 cells and via single-pass intestinal perfusion method. METHOD: Three self-emulsifying drug delivery systems were prepared and characterized in terms of pH, viscosity, droplet size, zeta potential, polydispersity index, conductivity, etc. Each formulation underwent 10, 100, 200, and 500 times dilution in intestinal buffer pH 6.8 and stomach buffer pH 1.2, respectively. Female Sprague Dawley rats were employed for in situ single-pass intestinal perfusion investigations. RESULTS: Results of the study revealed that the ideal self-emulsifying drug delivery systems formulation showed narrow droplet size, ideal zeta potential, and no conductivity. Additionally, as compared to the control groups, the optimum formulation had better apparent permeability (12.74 ± 0.02×10-4) from Caco-2 cell monolayer permeability experiments. The study also revealed greater Peff values (2.122 ± 0.892×10-4 cm/s) for the optimal formulation from in situ intestinal perfusion analyses in comparison to control groups (Domperidone; 0.802±0.418×10-4 cm/s). CONCLUSION: To conclude, prepared formulations can be a promising way of oral administration of Biopharmaceutical Classification System Class II drugs.

New Era on Combining Both Imaging and Drug Delivery to Treat Cancer.

It is well documented that cancer is one of the leading causes of death worldwide. During the pandemic, cancer screening was suspended, and only symptomatic patients were referred for screening. It is believed that deaths related to various cancer types have increased by around 10%, and the screening suspension was assumed as the main reason. It is well documented that the early diagnosis of cancer is important for the outcome; last decades, the introduction of nanotechnology-based carriers, which can serve as both imaging and therapeutic modalities, has risen. Although the combination of imaging and drug delivery for targeting cancer is a hopeful field, it is still under investigation and has not met clinical standards. Nanotheranostics, as they are also referred to, can combine both imaging and delivery and improve the survival rates and overall quality of life of patients. Would cancer patients have a chance to live a normal life if nano theranostics were incorporated into the daily clinical oncology practice? This review tries to answer this question by providing the most current applications of nanotheranostics targeting different types of cancer and summarizing their most significant characteristics.

Polymer based Gels: Recent and Future Applications in Drug Delivery Field.

BACKGROUND: Currently, there is ongoing research in the pharmaceutical technology field to develop innovative drug delivery systems with improved therapeutic efficacy. OBJECTIVES: Although there is a high need for new drug molecules, most scientists focus on the advancement of novel pharmaceutical formulations since the present excipients lack important properties such as low release rate leading to repeated dosing. Aside from this, pharmaceutical technologists aim to develop drug formulations that can target specific organs and tissues, lowering the possibility of adverse effects. METHODS: This review aims to cover the different polymer-based gel types, the development and characterization methods, as well as applications thereof. Finally, the recent advancements and future perspectives focusing on radiolabeled gels will be addressed. RESULTS: In the last decades, polymer based pharmaceutical gels have shown attractive properties and therefore have raised the attention of pharmaceutical scientists. Gels are either chemically or physically cross-linked networks that can absorb fluids such as water (hydrogels), oil (organogels) and even air(aerogels). A variety of polymers, either synthetic or natural, have been employed as components for the gels. Stimuli-responsive gels based on stimuli-sensitive polymers are among the most studied gel class of last years. CONCLUSION: The use of polymer-based gels as drug delivery systems would be beneficial for targeting numerous diseases.

Protein and Gene Delivery Systems for Neurodegenerative Disorders: Where Do We Stand Today?

It has been estimated that every year, millions of people are affected by neurodegenerative disorders, which complicate their lives and their caregivers' lives. To date, there has not been an approved pharmacological approach to provide the complete treatment of neurodegenerative disorders. The only available drugs may only relieve the symptoms or slow down the progression of the disease. The absence of any treatment is quite rational given that neurodegeneration occurs by the progressive loss of the function or structure of the nerve cells of the brain or the peripheral nervous system, which eventually leads to their death either by apoptosis or necrotic cell death. According to a recent study, even though adult brain cells are injured, they can revert to an embryonic state, which may help to restore their function. These interesting findings might open a new path for the development of more efficient therapeutic strategies to combat devastating neurodegenerative disorders. Gene and protein therapies have emerged as a rapidly growing field for various disorders, especially neurodegenerative diseases. Despite these promising therapies, the complete treatment of neurodegenerative disorders has not yet been achieved. Therefore, the aim of this review is to address the most up-to-date data for neurodegenerative diseases, but most importantly, to summarize the available delivery systems incorporating proteins, peptides, and genes that can potentially target such diseases and pass into the blood-brain barrier. The authors highlight the advancements, at present, on delivery based on the carrier, i.e., lipid, polymeric, and inorganic, as well as the recent studies on radiopharmaceutical theranostics.

Phytochemical Compounds Loaded to Nanocarriers as Potential Therapeutic Substances for Alzheimer's Disease-Could They be Effective?

Alzheimer's disease accounts for a high percentage of dementia cases in elderly individuals. This type of brain disease is caused by damage to the brain cells affecting the ability of the patients to communicate, as well as their thinking, behavior, and feelings. Although numerous research laboratories focus on advancements in treating Alzheimer's disease, the currently approved pharmacological approaches seem to only alleviate the symptoms. Consequently, there is an urgent need for alternative pharmacological options that can prevent the progressive impairment of neurons. Natural substances were used in ancient times to treat various disorders given their biological activities such as antioxidant, anti-inflammatory, and antiapoptotic properties. Besides, their cost-effectiveness and accessibility to anyone who needs them are their most significant characteristics. Therefore, the possible use of phytochemical compounds for the possible management or even prevention of Alzheimer's disease is currently under investigation. This review article summarizes the present status of Alzheimer's disease diagnosis and underlying mechanisms, the potential phytochemicals and their carriers, along with future perspectives. In the future, natural substances can play a role as an adjunct therapy for neurodegenerative forms of dementia, such as Alzheimer's disease.

Chitosan-bovine serum albumin-Carbopol 940 nanogels for mupirocin dermal delivery: ex-vivo permeation and evaluation of cellular binding capacity via radiolabeling.

The goal of this study was to develop and examine the nanogel-based topical delivery system of mupirocin. Nanogels were prepared with chitosan and bovine serum albumin by ionic gelation and Carbopol 940 was added to improve the gelling/adhesive properties. Detailed characterization studies were performed and the cellular binding capacity of radiolabeled nanogels was investigated on CCD-1070Sk cell lines. Results indicate the successful formation of nanogels with particle size and zeta potential ranged between 341.920-603.320 nm and 13.120-24.300 mV, respectively. The mechanical and rheological studies proved pseudoplastic and strong elastic gel behavior (G' > G''). Mupirocin was successfully entrapped into nanogels with a ratio of more than 95% and the loaded drug was slowly released up to 93.89 ± 3.07% within 24 h. The ex vivo penetration and permeation percentages of mupirocin were very low (1.172 ± 0.202% and 0.161 ± 0.136%) indicating the suitability of nanogels for dermal use against superficial skin infections. The microbiological studies pointed out the effectiveness of nanogels against Staphylococcus aureus strains. Nanogels did not show toxicity signs and the cell binding capacity of radiolabeled formulations was found to be higher than [99mTc]NaTcO4 to CCD-1070Sk cell line. Overall, mupirocin nanogels might be considered as a potential and safe topical treatment option for bacterial skin infections.

Current Status of Pediatric Formulations for Chronic and Acute Children' Diseases: Applications and Future Perspectives.

Infants and other children can be affected by various acute, chronic and many of them rare illnesses. Developing drugs for children is very challenging since they cannot intake tablets or hard oral solid dosage forms. Besides, most of the prescribed pediatric medications are unlicensed. The biggest issue that clinicians have to solve is that dosing in children is not based on weight or surface area of the body, as it happened in adults but is related to age variations in drug absorption, distribution, metabolism, and elimination. Thus, for pediatric patients, various therapeutic approaches have been proposed so as to develop suitable formulations such as liquid dosage forms, flexible capsules, milk-based products, etc. In addition, the administration of current pharmaceutical products to children might lead to some serious side effects which can also happen in adults but with a lower risk. Especially, infants are at high risk of getting poisoned by taking drugs used for adults. Moreover, children are very sensitive to the taste and smell of some pharmaceutical vehicles and can resist to intake them and this situation leads parents to search for tasteless and odorless medications. In this study, the current formulations for various diseases intended to be used in pediatric patients as well as various chronic and acute diseases of childhood are summarized. Authors believe that this review can help professionals who want to work with pediatric formulations to design more efficient and child-friendly drug delivery systems.

Ocular microemulsion of brinzolamide: Formulation, physicochemical characterization, and in vitro irritation studies based on EpiOcular™ eye irritation assay.

In recent years, the hydrophobic active substances have led researchers to develop new formulations to enhance bioavailability and dissolution rate; brinzolamide, a lipophilic drug belongs to carbonic anhydrase inhibitors, which cause reduction of intraocular pressure in patients suffering from glaucoma. Currently, the marketed product of brinzolamide is in the form of ocular drops; nonetheless, the conventional drops provide decreased therapeutic efficacy owing to their low bioavailability and pulsed drug release. Thus, the development of novel ocular formulations such as topical microemulsions is of high importance. In this work, the preparation of new microemulsions containing brinzolamide (0.2, 0.5 and 1% w/w) and comprised from isopropyl myristate, tween 80 and span 20 and Cremophor EL was performed. The obtained microemulsions were further characterized for their physicochemical properties. In addition, Fourier Transformed-Infrared spectroscopy was used touate the compatibility of active ingredients and components. In vitro release studies along with kinetic modeling were performed using the dialysis membrane method in simulated tear fluid. Bioadhesion studies were performed using Texture analysis. Finally, in vitro ocular irritation based on EpiOcular™ Eye Irritation Test and cytocompatibility studies was performed to examine any possible harm on ocular cells and predict in vivo safety profile.

Novel Ocular Drug Delivery Systems: An Update on Microemulsions.

Sufficient ophthalmic drug delivery is still challenging for pharmaceutical technologists, despite various scientific efforts. Several ocular drug carriers have been designed to enhance bioavailability by prolonging the drug retention time. One of the current encouraging approaches is the utilization of colloidal carriers with the characteristic submicron-nanometer size. Microemulsions (MEs) are such colloid systems that present sizes between 5 and 200 nm with significant thermodynamic stability and low surface tension. In addition, MEs as topical ocular carriers can lead to great ocular drug adsorption due to their enhanced retention time. Furthermore, considering that MEs are stable for long time and various temperatures, their ocular application is of great interest. The aim of this study is to cover basic physicochemical principals of ocular MEs such as their possible size, stability, and therapeutic efficacy against various eye disorders. Thus, a comprehensive review for ocular drug delivery systems in the form of MEs that show promising characteristics as their stability and therapeutic efficiency is performed.

Design and characterization of nanocarriers loaded with Levofloxacin for enhanced antimicrobial activity; physicochemical properties, in vitro release and oral acute toxicity

Inorganic and carbon based nanomaterials are widely used against several diseases, such as cancer, autoimmune diseases as well as fungi and bacteria colonization. In this work, Santa Barbara Amorphous mesoporous silica (SBA), Halloysite Nanotubes (HNTs) and Multiwalled Carbon Nanotubes (CNTs) were loaded with fluoroquinolone Levofloxacin (LVF) to be applied as antimicrobial agents. The prepared via adsorption nanocarriers were characterized by Fourier-Transformed Spectroscopy, Scanning Electron Microscopy as well as High Pressure liquid Chromatography. In vitro release studies were carried out using Simulated Body Fluid at 37oC and data analyzed by various kinetic models showing slow dissolution over 12-24 hours. Antimicrobial studies showed improved antibacterial activity against Escherichia coli, Enterococcus faecalis, Listeria monocytogenes, Staphylococcus aureus, and Staphylococcus epidermidis compared to neat nanomaterials. CNTs were found to be the most promising candidates for LVF delivery and they were chosen to be further studied for their acute oral toxicity and histopathological examination using C57/Black mice. Histological examination depicted that drug loading did not affect mice organs morphology as well as hepatocyte degeneration, central vein degeneration and parenchymal necrosis scores. To conclude, the prepared nanomaterials present significant characteristics and can act as antimicrobial drug carriers; CNTs found to be safe candidates when orally fed to mice.

Preparation and evaluation of novel microemulsion-based hydrogels for dermal delivery of benzocaine.

The purpose of the current research was to prepare and evaluate the potential use of microemulsion-based hydrogel (MBH) formulations for dermal delivery of benzocaine (BZN). The pseudoternary-phase diagrams were constructed for various microemulsions composed of isopropyl myristate (IPM) as oil phase, Span 20, Tween 20, Tween 80, cremophor EL and cremophor RH40 as surfactants, ethanol as cosurfactant and distilled water as aqueous phase. Finally, concentration of BZN in microemulsions was 2% (w/w). The physicochemical properties, such as conductivity, viscosity, pH, droplet size, polydispersity index and zeta potential of microemulsions, were measured. Carbopol 940 was used to convert BZN-loaded microemulsions into gel form without affecting their structure. Furthermore, excised rat abdominal skin was used to compare permeation and penetration properties of BZN loaded M3 and M3BHs with BZN solution. According to ex vivo study results, BZN-loaded M3BH1 showed highest flux values and high release rate values, and furthermore, this gel formulation had low surfactant content. Finally, in order to learn the localization of formulations within the dermal penetration, formulations and BZN solution were labeled with red oil O and subjected to fluorescence observation. In conclusion, BZN-loaded MBHs could be offered as a promising strategy for dermal drug delivery.