Development of chitosan based β-carotene mucoadhesive formulation for skin cancer treatment

Mucopermeating nanoformulations can enhance mucosal penetration of poorly soluble drugs at their target site. In this work, thiolated chitosan (TCS)-lithocholic acid (LA) nanomicelles loaded with beta-carotene, a safe phytochemical with anticancer properties, were designed to improve the pharmaceutical and pharmacological drug profile. The TCS-LA nanomicelles were characterized by FTIR to confirm the presence of the thiol group that favors skin adhesion, and to corroborate the conjugation of hydrophobic LA with hydrophilic CS to form an amphiphilic polymer derivative. Their crystalline nature and thermal behavior were investigated by XRD and DSC analyses, respectively. According to DLS and TEM, their average size was <300 nm, and their surface charge was +27.0 mV. beta-carotene entrapment and loading efficiencies were 64 % and 58 %, respectively. In vitro mucoadhesion and ex vivo mucopenetration analyses further corroborated the potential of the nanoformulation to deliver the drug in a sustained manner under conditions mimicking cancer micro-environment. Anticancer studies in mice demonstrated that the loaded nanomicelles delayed skin cancer growth, as revealed by both morphological and biochemical parameters. Based on the results obtained herein, it can be concluded that drug-loaded TCS-LA is a novel, stable, effective and safe mucoadhesive formulation of beta-carotene for the potential treatment of skin cancer.Comunidad de MadridUniversidad de Alcal

Pharmacoinformatics approaches in the discovery of drug-like antimicrobials of plant origin

Medicinal plants have served as an important source for addressing the ailments of humans and animals alike. The emergence of advanced technologies in the field of drug discovery and development has helped in isolating various bioactive phytochemicals and developing them as drugs. Owing to their significant pharmacological benefits and minimum adverse effects, they not only serve as good candidates for therapeutics themselves but also help in the identification and development of related drug like molecules against various metabolic and infectious diseases. The ever-increasing diversity, severity and incidence of infectious diseases has resulted in an exaggerated mortality and morbidity levels. Geno-proteomic mutations in microbes, irrational prescribing of antibiotics, antimicrobial resistance and human population explosion, all call for continuous efforts to discover and develop alternated therapeutic options against the microbes. This review article describes the pharmacoinformatics tools and methods which are currently used in the discovery of bioactive phytochemicals, thus making the process more efficient and effective. The pharmacological aspects of the drug discovery and development process have also been reviewed with reference to the in silico activities. Communicated by Ramaswamy H. Sarm

Anti-MRSA potential of biogenic silver nanoparticles synthesized from hydroponically grown Foeniculum vulgare

Background: Antimicrobial-resistant superbugs are rapidly spreading globally. Methicillin-resistant Staphylococcus aureus (MRSA) is one of these superbugs for which effective antibiotics are urgently required. The development of resistance against synthetic compounds has led to the study and utilization of plant based antimicrobial options due to a greater sensitivity against the phytochemcials obtained from them. Fennel (Foeniculum vulgare), a therapeutic, aromatic and nutritionally important herb that grows worldwide has a number of phytochemicals of medicinal importance. These phytochemicals also have the potential to reduce Ag+ to Ag0, thereby, making them available for the green synthesis of silver nanoparticles. Usually, fennel grows under cool environment in well-drained soil. However, it is possible to grow it hydroponically in soilless conditions using water-based mineral nutrient solutions. The technique helps in attaining higher yields of plant biomass and, hence, the phytochemicals. Purpose: This study aimed to prepare a silver nanoparticles based formulation against MRSA-induced skin and soft tissue infections, by using fennel extract (FEHydro) obtained from hydroponically grown plants for better biomass and higher phytochemical content. Methods: Plants grown in hydroponic system were compared with soil grown for growth rate and phytochemical content. Spectrophotometric comparison of total flavonoids, phenols, alkaloids, tannins, carbohydrates, proteins and lipids was carried out between hydroponic fennel extract (FEHydro) and soil grown fennel extract (FESoil). After establishing the efficacy of the hydroponically grown plants, their extract FEHydro was used for AgNPs green synthesis. Fennel extract fabricated AgNPs (FEHydroNP) were tested in vitro against MRSA through disc diffusion, turbidometric and time kill assays. The fennel extract (FEHydro) and AgNPs (FEHydroNP) were, then, formulated in a polyvinyl pyrrolidone and ethylene cellulose (PVP-EC) hydrogel and characterized through in vivo burn model in BALB/c mice. Results: The hydroponic system was found to give efficient plant biomass turnover with phytochemical content comparable to soil cultivated fennel. Hydroponic fennel gained 0.81 inches more height per week and 1.23 more secondary branches per week than soil cultivated fennel. Spherical AgNPs were successfully obtained from the fennel extract of hydroponically grown plants. Moreover, enhanced in vitro anti-MRSA potential of FE NPs was observed with MIC 625 µg/ml and MBC 12,500 µg/ml. In vivo infection elimination in 7 days and skin reepithelization were observed in gross examination and through Hematoxylin &amp; Eosin (H&E) stained slides of treated mouse skin biopsy samples. Conclusion: This study suggests that the green-synthesized silver nanoparticles of Fennel showed a strong antibacterial effect against the clinical isolates of MRSA, both in vitro and in vivo, thereby, suggesting their potential use in plant-based complementary and alternative medicine

Image1_Development of mucoadhesive adapalene gel for biotherapeutic delivery to vaginal tissue.TIF

Purpose: Alternate formulation strategies need to be devised for improving the absorption and bioavailability of drug molecules administered through the intravaginal route. Enhancing the coating of vaginal mucosa can aid the achievement of this goal. The aim of the current study is to develop a mucoadhesive formulation having adequate adhesiveness, spreading, and viscosity profiles that can ensure good tissue absorption of adapalene upon intravaginal application.Method: A combination of mucoadhesive agents has been employed, including Carbopol-934, HPMC K-15M, and xanthan gum, in varying ratios to formulate five different gels. Furthermore, a cost-effective UV-spectroscopic analytical method was developed to quantify the amount of adapalene in tested samples, both of in vitro and in vivo origin. The analytical method was validated for different parameters, including specificity, linearity, range, accuracy, precision, and ruggedness. The modified USP-II apparatus was used for dissolution studies, while in vivo pharmacokinetic validation was performed in a murine model.Result: Of all the tested formulations, on the basis of the rheo-mechanical attributes, ACX3 performed better than the rest, including the commercially available intravaginal reference product. ACX3 had an average adhesion time of 12 min and a spread diameter of 37 mm. It showed 35 mm as average distance travelled by the diluted sample for leakage assessment. The analytical method developed for the adapalene muco-adhesive gel was within the range for all the validation parameters. For further evaluating the performance of the formulation, dissolution studies were conducted in simulated vaginal conditions which showed 94.83% of drug release within 5 minutes, while on completion of 30 min, it was measured to be 92.90%. Moreover, approximately 67% of the administered drug was recovered after 5 min of administration as evaluated through tissue recovery procedures in mice.Conclusion: The study aided in development of a formulation which can enhance the muco-adhesion of the drug molecule, resulting in an improved pharmacokinetic profile. Moreover, it established an efficient assay method which can be employed for in vitro and in vivo quantification of adapalene in simulated and physiological fluids.</p

Table1_Development of mucoadhesive adapalene gel for biotherapeutic delivery to vaginal tissue.DOCX

Purpose: Alternate formulation strategies need to be devised for improving the absorption and bioavailability of drug molecules administered through the intravaginal route. Enhancing the coating of vaginal mucosa can aid the achievement of this goal. The aim of the current study is to develop a mucoadhesive formulation having adequate adhesiveness, spreading, and viscosity profiles that can ensure good tissue absorption of adapalene upon intravaginal application.Method: A combination of mucoadhesive agents has been employed, including Carbopol-934, HPMC K-15M, and xanthan gum, in varying ratios to formulate five different gels. Furthermore, a cost-effective UV-spectroscopic analytical method was developed to quantify the amount of adapalene in tested samples, both of in vitro and in vivo origin. The analytical method was validated for different parameters, including specificity, linearity, range, accuracy, precision, and ruggedness. The modified USP-II apparatus was used for dissolution studies, while in vivo pharmacokinetic validation was performed in a murine model.Result: Of all the tested formulations, on the basis of the rheo-mechanical attributes, ACX3 performed better than the rest, including the commercially available intravaginal reference product. ACX3 had an average adhesion time of 12 min and a spread diameter of 37 mm. It showed 35 mm as average distance travelled by the diluted sample for leakage assessment. The analytical method developed for the adapalene muco-adhesive gel was within the range for all the validation parameters. For further evaluating the performance of the formulation, dissolution studies were conducted in simulated vaginal conditions which showed 94.83% of drug release within 5 minutes, while on completion of 30 min, it was measured to be 92.90%. Moreover, approximately 67% of the administered drug was recovered after 5 min of administration as evaluated through tissue recovery procedures in mice.Conclusion: The study aided in development of a formulation which can enhance the muco-adhesion of the drug molecule, resulting in an improved pharmacokinetic profile. Moreover, it established an efficient assay method which can be employed for in vitro and in vivo quantification of adapalene in simulated and physiological fluids.</p