Utilizing Natural Mucoadhesive Polymers for Development of Nanoparticle Based Cilnidipine Buccal Films

The less oral bioavailability of Cilnidipine is primarily due to low solubility leads to reduced therapeutic efficacy. The study aimed to develop mucoadhesive buccal films to increase the bioavailability resulting in improved efficacy of this pooly soluble drug trough the buccal mucosa for the treatment of hypertension. Buccal films of Cilnidipine nanoparticles were developed by using different concentration of polymers such as HPMS K4M, HPMC K15M and Carbopol 934 by solvent casting technique. The developed films were characterized for the surface texture, thickness, surface pH, folding endurance, swelling index, content uniformity, mucoadhesive strength, moisture loss, moisture absorption, drug release, ex-vivo drug permeation and stability studies. F9 formulation was optimized as best formulation based on the physico chemical parameters, in vitro dissolution and ex-vivo permeation studies. The result indicates that the drug releases from the buccal films are slow and prolonged over the period of 12 h. There was no significance changes were observed during the stability studies indicates that, the prepared buccal films are stable. Hence, mucoadhesive buccal films can be used as an alternative particularly in the bed time with improved absorption of the dug through buccal mucosa, resulting in better bioavailability and therapeutic efficacy

FORMULATION AND EVALUATION OF IN-SITU GEL CONTAINING LINEZOLID IN THE TREATMENT OF PERIODONTITIS

Objective: The intent to prepare and evaluate Linezolid in-situ gel in the treatment of periodontitis. Methods: pH-sensitive in-situ gel was formed by the cold method using a varying concentration of the drug, carbopol 934P and hydroxypropyl methylcellulose (HPMC) and carbopol 934P and sodium carboxy methylcellulose (CMC) (1:1,1:1.5,1:2,1:2.5). An optimized batch was selected based on gelling time and gelling capacity. The prepared in-situ gels were evaluated for appearance, pH, gelling capacity, viscosity, in vitro release studies, rheological studies, and finally, was subjected to drug content estimation and antibacterial activity test. Results: FTIR study shows drug and physical mixture were compatible with each other. The rheology of formulated in-situ gel exhibited a pseudoplastic flow pattern. this may be because when polymer concentration was increased the prepared formulations become more viscous and in turn delayed the drug release and from the prepared formulation, LF4 and SF4 have polymer concentrations i. e, 0.9% carbopol and sodium CMC showed drug release up to 12 h. Conclusion: When carbopol is appropriately mixed with other suitable polymers it forms an in-situ gel-forming system that was substantiated by the property to transform into stiff gels when the pH is increased. The in-situ gel was prepared using a combination of carbopol-HPMC and carbopol-Na CMC The formulations LF1 to SF4 showed high linearity (R2 = 0.490-0.682), indicating that the drug was released from the prepared in-situ gel by the diffusion-controlled mechanism. Thus, the formulation of batches LF4 and SF4 containing carbopol: HPMC and carbopol: NaCMC in 1:2 ratios were considered as optimum formulation based on optimum viscosity, gelling capacity and to extend the in vitro drug release

Therapeutic effects of Crataegus monogyna inhibitors against breast cancer

Breast cancer is a silent killer disorder among women and a serious economic burden in healthcare management. Every 19 s, a woman is diagnosed with breast cancer, and every 74 s, a woman worldwide passes away from the disease. Despite the increase in progressive research, advanced treatment approaches, and preventive measures, breast cancer rates continue to increase. This study provides a combination of data mining, network pharmacology, and docking analysis that surely could revolutionize cancer treatment by exploiting prestigious phytochemicals. Crataegus monogyna is a small, rounded deciduous tree with glossy, deeply lobed leaves and flat sprays of cream flowers, followed by dark red berries in autumn. Various studies demonstrated that C. monogyna is therapeutically effective against breast cancer. However, the particular molecular mechanism is still unknown. This study is credited for locating bioactive substances, metabolic pathways, and target genes for breast cancer treatment. According to the current investigation, which examined compound–target genes–pathway networks, it was found that the bioactive compounds of C. monogyna may operate as a viable solution against breast cancer by altering the target genes implicated in the disease pathogenesis. The expression level of target genes was analyzed using GSE36295 microarray data. Docking analysis and molecular dynamic simulation studies further strengthened the current findings by validating the effective activity of the bioactive compounds against putative target genes. In summary, we propose that six key compounds, luteolin, apigenin, quercetin, kaempferol, ursolic acid, and oleanolic acid, contributed to the development of breast cancer by affecting the MMP9 and PPARG proteins. Integration of network pharmacology and bioinformatics revealed C. monogyna’s multitarget pharmacological mechanisms against breast cancer. This study provides convincing evidence that C. monogyna might partially alleviate breast cancer and ultimately lays a foundation for further experimental research on the anti-breast cancer activity of C. monogyna

From seeds to survival rates: investigating Linum usitatissimum’s potential against ovarian cancer through network pharmacology

Ovarian cancer is a malignant tumor that primarily forms in the ovaries. It often goes undetected until it has spread to the pelvis and abdomen, making it more challenging to treat and often fatal. Historically, natural products and their structural analogues have played a pivotal role in pharmacotherapy, especially for cancer. Numerous studies have demonstrated the therapeutic potential of Linum usitatissimum against ovarian cancer, but the specific molecular mechanisms remain elusive. This study combines data mining, network pharmacology, and molecular docking analysis to pioneer an innovative approach for ovarian cancer treatment by identifying potent phytochemicals. Findings of current study revealed that Apigenin, Vitamin E, Palmitic acid, Riboflavin, Isolariciresinol, 5-Dehydro-avenasterol, Cholesterol, Pantothenic acid, Nicotinic acid, Campesterol, Beta-Sitosterol, Stigmasterol, Daucosterol, and Vitexin suppress tumor growth by influencing AKT1, JUN, EGFR, and VEGFA. Kaplan–Meier survival analysis spotlighted AKT1, JUN, EGFR, and VEGFA as potential diagnostic and prognostic biomarkers for ovarian cancer. However, it is imperative to conduct in vivo and in vitro examinations to ascertain the pharmacokinetics and biosafety profiles, bolstering the candidacy of L. usitatissimum in ovarian cancer therapeutics

Combinational effect of angiotensin receptor blocker and folic acid therapy on uric acid and creatinine level in hyperhomocysteinemia-associated hypertension

© 2019 International Union of Biochemistry and Molecular Biology, Inc. Homocysteine [HSCH2CH2CH(NH2)COOH] (Hcy) is a sulfur-containing amino acid of 135.18 Da of molecular weight, generated during conversion of methionine to cysteine. If there is a higher accumulation of Hcy in the blood, that is usually above 15 µmol/L, it leads to a condition referred to as hyperhomocysteinemia. A meta-analysis of observational study suggested an elevated concentration of Hcy in blood, which is termed as the risk factors leading to ischemic heart disease and stroke. Further experimental studies stated that Hcy can lead to an increase in the proliferation of vascular smooth muscle cells and functional impairment of endothelial cells. The analyses confirmed some of the predictors for Hcy presence, such as serum uric acid (UA), systolic blood pressure, and hematocrit. However, angiotensin-converting enzyme inhibitors angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) alone are inadequate for controlling UA and creatinine level, although the addition of folic acid may be beneficial in hypertensive patients who are known to have a high prevalence of elevated Hcy. We hypothesized that combination therapy with an ARB (olmesartan) and folic acid is a promising treatment for lowering the UA and creatinine level in hyperhomocysteinemia-associated hypertension

1,2,3-Triazolyl-tetrahydropyrimidine conjugates as potential Sterol Carrier Protein-2 Inhibitors: Larvicidal activity against the Malaria Vector Anopheles arabiensis and In Silico Molecular Docking Study

Alteration of insect growth regulators by the action of inhibitors is becoming an attractive strategy to combat disease-transmitting insects. In the present study, we investigated the larvicidal effect of 1,2,3-triazolyl-pyrimidinone derivatives against the larvae of the mosquito Anopheles arabiensis, a vector of malaria. All compounds demonstrated insecticidal activity against mosquito larvae in a dose-dependent fashion. A preliminary study of the structure–activity relationship indicated that the electron-withdrawing substituent in the para position of the 4-phenyl-pyrimidinone moiety enhanced the molecules’ potency. A docking study of these derivatives revealed favorable binding affinity for the sterol carrier protein-2 receptor, a protein present in the intestine of the mosquito larvae. Being effective insecticides against the malaria-transmitting Anopheles arabiensis, 1,2,3-triazole-based pyrimidinones represent a starting point to develop novel inhibitors of insect growth regulators.Fil: Venugopala, Katharigatta N.. Durban University Of Technology; Sudáfrica. King Faisal University; Arabia SauditaFil: Shinu, Pottathil. King Faisal University; Arabia SauditaFil: Tratrat, Christophe. King Faisal University; Arabia SauditaFil: Deb, Pran Kishore. Philadelphia University Jordan; JordaniaFil: Gleiser, Raquel M.. Universidad Nacional de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Instituto Multidisciplinar de Biología Vegetal (P). Grupo Vinculado Centro de Relevamiento y Evaluación de Recursos Agrícolas y Naturales; ArgentinaFil: Chandrashekharappa, Sandeep. National Institute Of Pharmaceutical Education And Research, Raebareli; IndiaFil: Chopra, Deepak. Indian Institute Of Science Education And Research Bhopal; IndiaFil: Attimarad, Mahesh. King Faisal University; Arabia SauditaFil: Nair, Anroop B.. King Faisal University; Arabia SauditaFil: Sreeharsha, Nagaraja. Vidya Siri College Of Pharmacy; India. King Faisal University; Arabia SauditaFil: Mahomoodally, Fawzi M.. University Of Mauritius; MauricioFil: Haroun, Michelyne. King Faisal University; Arabia SauditaFil: Kandeel, Mahmoud. Faculty Of Veteinary Medicine; Egipto. King Faisal University; Arabia SauditaFil: Asdaq, Syed Mohammed Basheeruddin. Almaarefa University; Arabia SauditaFil: Mohanlall, Viresh. Durban University Of Technology; SudáfricaFil: Al-Shari, Nizar A.. Jordan University Of Science And Technology; JordaniaFil: Morsy, Mohamed A.. King Faisal University; Arabia Saudita. Faculty Of Medicine; Egipt

Nanotechnology integration for sars-cov-2 diagnosis and treatment: An approach to preventing pandemic

The SARS-CoV-2 outbreak is the COVID-19 disease, which has caused massive health devastation, prompting the World Health Organization to declare a worldwide health emergency. The corona virus infected millions of people worldwide, and many died as a result of a lack of particular medications. The current emergency necessitates extensive therapy in order to stop the spread of the coronavirus. There are various vaccinations available, but no validated COVID-19 treatments. Since its outbreak, many therapeutics have been tested, including the use of repurposed medications, nucleoside inhibitors, protease inhibitors, broad spectrum antivirals, convalescence plasma therapies, immune-modulators, and monoclonal antibodies. However, these approaches have not yielded any outcomes and are mostly used to alleviate symptoms associated with potentially fatal adverse drug reactions. Nanoparticles, on the other hand, may prove to be an effective treatment for COVID-19. They can be designed to boost the efficacy of currently available antiviral medications or to trigger a rapid immune response against COVID-19. In the last decade, there has been significant progress in nanotechnology. This review focuses on the virus’s basic structure, pathogenesis, and current treatment options for COVID-19. This study addresses nanotechnology and its applications in diagnosis, prevention, treatment, and targeted vaccine delivery, laying the groundwork for a successful pandemic fight

Multifunctional Mesoporous Silica Nanoparticles for Oral Drug Delivery

Nanotechnology has transformed engineering designs across a wide spectrum of materials and applications. Mesoporous Silica Nanoparticles (MSNs) are one of the new fabrications of nanostructures as medication delivery systems. MSNs have pore sizes varying from 2 to 50 nm, making them ideal for a variety of biological applications. They offer unique characteristics such as a tunable surface area, well-defined surface properties, and the ability to improve drug pharmacokinetic characteristics. Moreover, they have the potential to reduce adverse effects by delivering a precise dose of medications to a specific spot rather than the more frequent systemic delivery, which diffuses across tissues and organs. In addition, the vast number of pores allow drug incorporation and transportation of drugs to various sites making MSNs a feasible platform for orally administered drugs. Though the oral route is the most suitable and convenient platform for drug delivery, conventional oral drug delivery systems are associated with several limitations. Surpassing gastrointestinal barriers and the low oral bioavailability of poorly soluble medicines pose a major challenge in the pharmaceutical industry. This review provides insights into the role of MSNs and its mechanism as an oral drug delivery system

Formulation-by-Design of Efinaconazole Spanlastic Nanovesicles for Transungual Delivery Using Statistical Risk Management and Multivariate Analytical Techniques

As regulatory and technical landscapes for pharmaceutical formulation development are rapidly evolving, a risk-management approach using multivariate analysis is highly essential for designing a product with requisite critical quality attributes (CQA). Efinaconazole, a newly approved poorly water-soluble antifungal triazole drug has poor permeability. Spanlastics, new-generation surfactant nanovesicles, being fluidic, help improve the permeability of drugs. Therefore, we optimized efinaconazole spanlastics using the concepts of Formulation-by-Design (FbD) and explored the feasibility of transungual delivery for the management of onychomycosis. Using the Ishikawa fishbone diagram, the risk factors that may have an impact on the CQA of efinaconazole spanlastic vesicles were identified. Application of the Plackett–Burman experimental design facilitated the screening of eight different formulation and process parameters influencing particle size, transmittance, relative deformability, zeta potential, entrapment efficiency, and dissolution efficiency. With the help of Pareto charts, the three most significant factors were identified, viz., vesicle builder (Span), edge activator (Tween), and mixing time. The levels of these three critical variables were optimized by FbD to reduce the particle size and maximize the transparency, relative deformability, encapsulation efficiency, and dissolution efficiency of efinaconazole spanlastic nanovesicles. Bayesian and Lenth’s analysis and mathematical modeling of the experimental data helped to quantify the critical formulation attributes required for getting the formulation with optimum quality features. The optimized efinaconazole-loaded spanlastic vesicles had a particle size of 197 nm, transparency of 91%, relative deformability of 12.5 min, and dissolution efficiency of 81.23%. The spanlastic formulation was incorporated into a gel and explored ex vivo for transungual delivery. This explorative study provides an example of the application of principles of risk management, statistical multivariate analysis, and the FbD approach in developing efinaconazole spanlastic nanovesicles

Topical Nanoemulgel for the Treatment of Skin Cancer: Proof-of-Technology

The present study is a mechanistic validation of ‘proof-of-technology’ for the effective topical delivery of chrysin nanoemulgel for localized, efficient treatment of melanoma-affected skin. Background: Currently available treatments for skin cancer are inefficient due to systemic side effects and poor transcutaneous permeation, thereby presenting a formidable challenge for the development of novel nanocarriers. Methods: We opted for a novel approach and formulated a nanocomplex system composed of hydrophobic chrysin dissolved in a lipid mix, which was further nanoemulsified in Pluronic® F-127 gel to enhance physicochemical and biopharmaceutic characteristics. Chrysin, a flavone extracted from passion flowers, exhibits potential anti-cancer activities; however, it has limited applicability due to its poor solubility. Pseudo-ternary phase diagrams were constructed to identify the best self-nanoemulsifying region by varying the compositions of oil, Caproyl® 90 surfactant, Tween® 80, and co-solvent Transcutol® HP. Chrysin-loaded nanoemulsifying compositions were characterized for various physicochemical properties. Results: This thermodynamically stable, self-emulsifying drug delivery system showed a mean droplet size of 156.9 nm, polydispersity index of 0.26, and viscosity of 9100 cps after dispersion in gel. Mechanical characterization using Texture Analyzer exhibited that the gel had a hardness of 487 g and adhesiveness of 500 g. Ex vivo permeation through rat abdominal skin revealed significant improvement in percutaneous absorption measured as flux, the apparent permeability coefficient, the steady-state diffusion coefficient, and drug deposition. In vitro cytotoxicity on A375 and SK-MEL-2 cell lines showed a significantly improved therapeutic effect, thus ensuring reduction in dose. The safety of the product was established through biocompatibility testing on the L929 cell line. Conclusion: Aqueous, gel-based, topical, nanoemulsified chrysin is a promising technology approach for effective localized transcutaneous delivery that will help reduce the frequency and overall dose usage and ultimately improve the therapeutic index