Current Drug Therapy - Volume 18, Issue 2, 2023

Silymarin, is a phytoactive constituent isolated from the fruits and seeds of Silybum marianum L Gaetn.), also called milk thistle belonging to the family of Asteracease. The phytoactive has been used to treat several physiological disorders. The objective of this manuscript was to review the therapeutic prospective of silymarin due to its ability to treat several physiological disorders. The databases such as Pubmed, Elsevier, and Google Scholar were reviewed for the investigations or reviews published related to the title. The discussion is focused on the immunomodulatory, chemopreventive, and anti-inflammatory mechanisms of silymarin in various metabolic and dermatological disorders. In addition, the review discusses the different therapeutic potentials of silymarin such as the management of the liver disorder, skin carcinogenesis, cardiovascular disorders, diabetes mellitus, neurodegenerative disorders, and several dermatological disorders such as melasma, anti-aging, acne, rosacea, atopic dermatitis, and psoriasis. Silymarin is safe even with a dose higher than the therapeutic dose. Silymarin had good potential for the safe and effective treatment of numerous metabolic and dermatological disorders.

Natural cells have become an area of interest due to their biocompatibility, nonimmunogenicity, biodegradability, and targeting specificity. The human vascular system retains distinctive physiological features that can be developed for enhanced and effective targeted drug delivery. Red blood cells (RBCs) have unique features and properties that make them potential natural carriers for numerous substances. Recently, the RBC membrane has become a unique biological carrier and it has been extensively studied due to its long-circulating half-life, low toxicity, high stability and the ability to transport various biologically active substances with higher drug release efficiency. Among the benefits of the RBC membrane as a drug delivery carrier in medical and biological fields is the use of this system in anticancer therapy. Antitumor drugs are loaded in gold NP, magnetic NPs, or mesoporous silica NPs. Then, the loaded NP is used as a core and coated with an RBC membrane to protect the NP from immune attack and enhance drug targeting. Moreover, RBCs have been used for encapsulating different enzymes to overcome the undesirable outcomes associated with enzyme replacement therapy. This review highlighted the most recent RBC membrane preparation methods, such as Membrane coating technology and Osmotic Loading Procedures. The recent advances in the design of RBC membrane carriers and discuss the applications of RBCs in different fields such as therapeutic enzymes, immunotherapy and anti-tumour therapy. Given the potential risks and challenges in the development of any treatment protocol, this review elucidated the problematic aspects and prospects, describing new modalities to overcome these problems. RBCs as a drug carriers are among the most interesting topics as a novel drug delivery system as they are convenient, effective, safer, biocompatible and have good properties to deliver and administrate the drug specifically to the target site of action with fewer side effects and interference with therapeutic aspects.

Background: Now-a-day, there is a need to explore the concept of green chemistry in every field. Many existing conventional and novel drug delivery systems have problems related to green chemistry. Anewer natural dosage form pastilles were explored to overcome the existing limitations of the different dosage forms. Objective: The present study aims to optimize the Glipizide (GPZ) matrix pastilles using waxy erodible polymers, integrating the concept of quality by design (QbD) and green chemistry. Methods: The pastilles were formulated using the fabricated lab-scale pastillator. GPZ was used as a model drug. The concern related to the drug is low aqueous solubility and short variable half-life. The solubility of the drug was improved by formulating a complex between GPZ and chemically modified ß –cyclodextrin (β-CD) - hydroxypropyl-ß-cyclodextrin (HP-ß-CD). The complex was prepared using the kneading method. The complex was formulated and incorporated in different stoichiometric ratios of GPZ: complexing agent. Sustained-release pastille was formulated using Gelucire 43/01 (GC 43/01) as a release retardant polymer. The central composite design was used to obtain an optimum batch, using the amount of GC 43/01 and temperature as independent variables, while drug release at 2h, 6h, and 10h was chosen as dependent variables. The design batches were evaluated for post-and pre formulation parameters. An optimum formulation was evaluated for the influence of hydroalcoholic media on drug release. Results: The complex formulated using HP-ß-CD (1:1) shown better solubility (36.5 mg/ml) and dissolution. The complex was incorporated in the pastilles with erodible polymer GC 43/01. The formulation was found robust with optimum pre and post-formulation parameters. An optimized batch was chosen from the design space of central composite design. The drug release of the optimized formulation was found 29.13%, 57.29% and 85.70% at 2, 6 and 10 hrs respectively, similar to the drug release of the marketed formulation. As the amount of alcohol increased from 5 to 40 %, the drug release also increased but did not show a dose dumping effect. It was due to the altered solubility of GPZ in alcohol. Conclusion: The new formulation, Pastilles of GPZ were developed incorporating the waxy erodible polymer. Pastilles were capable of controlling drug release for up to 12 h. The amount of GC 43/01 and temperature had a significant effect on the formulation of GPZ sustained-release pastille. The newer approach of formulating pastilles might apply to the industry as it is an eco-friendly, single-step process with fewer excipients.

Background: Oral apremilast, a selective phosphodiesterase-4 inhibitor, is effective in the treatment of moderate to severe plaque psoriasis and acute psoriatic arthritic disease. According to BCS categorization, it is a class IV medication, which denotes low solubility and lesser permeability through the skin. Objective: The objective of the research is to develop a nanoemulsion that will increase apremilast’s skin permeability. Utilizing a simplex lattice design, an optimised nanoemulsion has been developed, and then transformed into a gel form and created as a nanoemulgel. Methods: The nanoemulsion was developed by selecting the oil, surfactant, co-surfactant, and cosolvent, in that order, based on the solubility study, and was then evaluated based on various criteria. Different grades and concentrations of carbopol polymer were used to make nanoemulgel, which was then tested for physicochemical parameters like pH, viscosity, spreadability, extrudability, percentage of drug content, percentage of drug diffusion, skin permeation, and skin retention. For skin irritancy tests, male Wistar albino rats weighing between 200 and 250 g were used to find out how likely it was that apremilast-loaded nanoemulgel would cause skin irritation. Results: The nanoemulsion formulation A5 containing 10% Captex 355 and 40% Smix in a 3:1 ratio of Cremophore RH 40: Labrafil showed the smallest particle size and greatest drug diffusion. In comparison to other formulations of emulgel, the 0.75 % concentration of carbopol 940 produced the best results. Conclusion: A stable nanoemulgel system with apremilast loaded was created, and a number of process factors were assessed. The optimised batch produced repeatable results when evaluated, exhibited no skin irritation, and was shown to be stable after three months at ambient conditions of temperature and humidity.

Background: After almost 30 years of study, it is a scientific fact that inflammation is the root cause of arthritis. Objective: Guggul has a beneficial role in arthritis because of its ability to neutralize the NF-kappa factor. A topical drug delivery system is beneficial to overcome the problems associated with oral drug delivery and offers several potential advantages. Ultra-deformable vesicles (UDVs) are a special type of liposome made up of phospholipids and surfactants, and they are highly flexible. Methods: In the present investigation, 20 formulations were suggested by Design Expert® 10 software (Central Composite Design) which were prepared using film hydration method with lecithin (70-90 mg), tween 80 (10–30 mg), Guggul extract (3 mg) and sonicated for 5–15 minutes. The formulation was optimized based on particle size (R130;) and maximum entrapment efficiency (R2). Results: The optimized formulation consists of 78.92 mg soya phosphatidyl choline (lecithin), 22.08 mg Tween 80, and 3 mg Guggul with a sonication time of 12.74 minutes that resulted in a particle size of 375.5 ±15.1 nm and entrapment efficiency of 80.3 ± 3.1%. Guggul UDVs showed more antioxidant activity compared to Guggul extract, control and standard. Similar results were obtained in the case of anti-arthritic activity, which was measured by egg albumin denaturation, bovine serum albumin denaturation, proteinase inhibitory action, and anti-lipoxygenase activity. The data of both activities were analyzed using an unpaired t-test to determine significant values (p < 0.05). Conclusion: These results demonstrate the potential of UDVs in the treatment of all arthritis diseases.

Background: Vulvovaginal candidiasis (VVC) is a common fungal infection of the vaginal area affecting 75% of women at least once in their lifetime. However, there is no clear evidence helping to choose the most effective treatment method to improve the symptoms of VVC. Objective: The objective of this study was to compare the effect of using honey with clotrimazole on the treatment of symptoms of VVC. Methods: All databases in English (Embase, MEDLINE, ProQuest, Google Scholar, Scopus, Cochrane Library, and Web of Science) and Persian (Irandoc, SID, and Magiran) were searched without time limitation. Evaluation of studies in terms of bias was performed using the Cochrane handbook. Four clinical trials were included in the present systematic review; however, only three of them were included in the meta-analysis. Results: The results of the meta-analysis demonstrated that the rate of positive culture after treatment (RR: 2.35; 95%CI: 1.45 to 3.82) was significantly higher in the honey group than in the clotrimazole one. The frequency of itching after treatment (RR: 0.25, 95%CI: 0.12 to 0.49) was significantly lower in the honey-receiving group than in the clotrimazole one. However, there was no statistically significant difference in the incidence of other symptoms of VVC, including vaginal discharge (RR: 0.26, 95%CI: 0.02 to 2.75), vaginal burning (RR: 0.35, 95%CI: 0.03 to 3.80) and dyspareunia (RR: 0.64, 95%CI: 0.27 to 1.50) between groups. Conclusion: Due to the low quality of the studies, more clinical trial studies with stronger designs in this field are needed to clearly identify the therapeutic effects of honey on improving the symptoms of VVC.

Background: In the development of multidrug resistance, efflux pumps effectively pump drug compounds out of cells, which results in reduced membrane permeability to drug compounds. This study evaluated the effect of gold nanoparticles on the inhibition of norA and norB efflux pumps in ciprofloxacin-resistant Staphylococcus aureus isolated from burn patients in Qom province, Iran. Methods: In this cross-sectional study, S. aureus strains were isolated from burn patients in Qom hospital, Iran. After gold nanoparticles were synthesized using chemical reduction and characterized by spectrophotometry, transmission electron microscopy (TEM), and dynamic light scattering (DLS), ciprofloxacin resistance of S. aureus was screened by the disc diffusion method. The Minimum Inhibitory Concentration (MIC) of ciprofloxacin (CCCP), ciprofloxacin + gold nanoparticles (CCCP + gold nanoparticles), and ciprofloxacin + CCCP was determined. Moreover, norA and norB genes were evaluated by PCR using special primers. Real-time PCR was then performed for norA and norB genes. Results: Of 88 S. aureus strains tested, 50 (56.81%) were resistant to ciprofloxacin. From the 50 ciprofloxacin-resistant S. aureus strains, 12 isolates had active pumps. Real-time PCR of 12 ciprofloxacin- resistant S. aureus and S. aureus ATCC 25923 before and after exposure to ciprofloxacin, gold nanoparticles, and gold nanoparticles with sub-MIC ciprofloxacin revealed significant differences in expression of norA and norB genes before exposure to the treatments compared to after exposure (p <0.05). Conclusion: Gold nanoparticles with ciprofloxacin could be used to prevent the expression of pump genes involved in resistance to fluoroquinolone compounds.