Current Drug Therapy - Volume 15, Issue 4, 2020

Treatment of skin ailments through systemic administration is limited due to toxicity and patients discomfort. Hence, lower risk of systemic side effects from topical dosage forms like ointments, creams, emulsions and gels is more preferred for the treatment of skin disease. Application of lipid based carriers in drug delivery in topical formulations has recently become one of the major approaches to improve drug permeation, safety, and effectiveness. These delivery systems include liposomes, ethosomes, transfersomes, Nanoemulsions (NEs), Solid Lipid Nanoparticles (SLNs) Nanostructured Lipid Carriers (NLCs) and micelles. Most of the liposomes and SLNs based products are in the market while some are under investigation. Transcutaneous delivery of therapeutics to the skin layer by novel lipid based carriers has enhanced topical therapy for the treatment of skin ailments. This article covers an overview of the lipid-based carriers for topical uses to alleviate skin diseases.

Diabetes Retinopathy (DR) is one of the main complications due to diabetes. DR will damage the retinal capillaries and block them, which causes the loss of vision. Different drugs and therapies are used for the treatment and prevention of the DR. The most commonly used treatment is laser technology and combination therapy, along with some drugs. But these drugs possess side effects in the form of cataract, glaucoma, and complete blindness of the eye. The main strategy to overcome In DR, medicines with minimum side effects or maximum therapeutic effects are used. This article emphasizes the current strategy used for the treatment of DR with allopathic as well as herbal drugs.

In the current era, many formulations have been designed in the form of vesicular carriers like liposomes and niosomes which have been proved to be one of the potential candidates for drug delivery by the oral route but due to the gastrointestinal environment i.e. pH, presence of enzymes, and bile salts, their use is limited. Because of these difficulties, research is being done to increase the stability and efficacy of the drug. Thus bilosomes have been developed as a potential vesicular carrier system for oral vaccine delivery, transdermal and parenteral targeted drug delivery. The present article covers various aspects related to the novel vesicular system that is based on bile salts called bilosomes, for targetted drug delivery systems. It includes information related to bilosome composition, formulation techniques, characterization methods, applications in oral immunization as vaccine delivery approach and advantages over conventional nanocarriers such as liposomes and niosomes. It also focuses on the stability and applications of bilosomes along with scalability and potentiality in biomedical field of oral immunization against various dreadful diseases.

Atopic Dermatitis (AD) is long-lasting degenerating skin disease with a characteristic phenotype and stereotypically spread skin lesions. The AD results due to a complex interface among genetic factors, host’s surroundings, pharmacological anomalies and immunological factors. In previous decades, researchers had shown marked interest due to increased prevalence in developed countries. In this review, basics along with the advances in pathogenesis and management of AD have been discussed. The immunological factors i.e. Innate Lymphoid Cells, IL-22 and Toll-like receptors have an important role in the pathogenesis. The proactive topical therapy by skincare, topical glucocorticosteroids and calcineurin inhibitors have improved effect in the management of AD. The human monoclonal antibody-based systemic drug (Duplimab) is a considerable advancement in the management of AD. Other monoclonal antibody-based drugs (Lebrikizumab, Tralokinumab, Apremilast and Nemolizumab) are in different phases of clinical trials. A better understanding of genetics and immunoregulatory cascade will lead to the development of efficacious drugs and better management therapy preventing the relapse of flares and improved life quality of AD patients.

Background: Development of effective cancer-chemotherapy is the most challenging field due to the toxicity of chemo-agents. Objective: As chalcone has been known to have pharmacological applications, here the aim is to synthesized three chalcone derivatives, 2',4'-dihydroxy-3,4-methylenedioxychalcone (C1), 2'-hydroxy- 2,4, 6-trimethoxychalcone (C2) and 2'-hydroxy-4-methylchalcone (C3) and investigate their anti-cancer properties against Ehrlich Ascites Carcinoma (EAC) cell. Methods: Anticancer properties against EAC cells were studied by examining growth inhibition, MTT assays, tumour-bearing mice survival, tumour weight measurement and haematological profiles. Moreover, apoptosis of EAC cells was investigated by fluorescence microscopy, flowcytometry and DNA fragmentation assays. Expression of apoptosis related genes were studied by reverse transcriptase-PCR (RT-PCR). Results: Among the compounds, C1 exhibited highest cell growth inhibition at 200 mg/kg/day (81.71%; P < 0.01). C1 treatment also increased the life span of EAC-bearing mice (82.60%, P < 0.05) with the reduction of tumour burden (22.2%, P < 0.01) compared to untreated EAC-bearing mice. In vitro study indicated that C1 killed EAC-cells in a dose-dependent manner and induced mitochondria-mediated apoptotic pathways. In addition, C1 treated cells exhibited increased apoptotic features such as membrane blebbing, chromatin condensation, and nuclear fragmentation after Hoechst 33342 staining. Increased fragmentation of DNA in gel electrophoresis followed by C1 treatment further confirmed apoptosis of EAC cells. EAC cells treated with C1 showed reduced Bcl-2 expression in contrast to notable upregulation of p53 and Bax expression. It implied that C1 could reinstate the expression of pro-apoptotic tumour suppressor and inhibit anti-apoptotic genes. Conclusions: Thus, C1 showed significant growth inhibitory properties and induced apoptosis of EAC cells.

Background: Lung is one of the radiosensitive and late responding organs, and is an important target for ionizing radiation. Radiation-induced pneumonitis and fibrosis are major consequences of lung exposure to a high dose of radiation and pose threats to the lives of exposed people. Mitigation of lung injury following an accidental radiation event or for patients with lung cancer is one of the most interesting issues in radiobiology. In the current study, we aimed to determine whether celecoxib, the most common cyclooxygenase-2 (COX-2) inhibitor, is able to mitigate pneumonitis and fibrosis following lung irradiation or not. Materials and Methods: 20 male mice were assigned to 4 groups: control, celecoxib treatment, radiation, and radiation plus celecoxib. Irradiation was performed with a dose of 18 Gy cobalt-60 (60Co) gamma rays. Celecoxib treatment (50 mg/kg) started 24 h after irradiation and continued four times per week for 4 weeks. Results: Irradiation of lung led to remarkable infiltration of macrophages, lymphocytes, mast cells and neutrophils. Also, a mild increase in fibrosis markers including accumulation of collagen, and alveolar and vascular thickening, was observed. Post-exposure treatment with celecoxib was able to mitigate fibrosis as well as alveolar and vascular changes, however, it was unable to mitigate pneumonitis markers. Conclusion: Celecoxib showed that it may have an anti-fibrosis effect following exposure of mice lung to radiation, although it was unable to prevent pneumonitis.

Background: Local anesthetics are widely used to decrease sensitivity to pain in specific regions of the body, while performing medical tasks. Many studies have probed the mechanism of action of local anesthetics but still, many questions remain. (2R-(-)2-(2, 6-dimethylphenylaminocarbonyl)- 1-methyl piperidinium chloride (DAMP), is an extensively used amide-type local anesthetic. Objective: This study aims at revealing the various electrophysical and chemical properties of the title compound. This study will be useful for future research by pharmacologists. Methods: Density Functional Theory (DFT) computations were executed using Gaussian’09 program package and were optimized with the B3LYP /6-311+G (d, p) basis set. Natural Bond Orbital (NBO) analysis was carried out with version 3.1. Normal Coordinate Analysis (NCA) was used to systematically calculate the harmonic vibrational wavenumbers. Molecular docking simulations were carried out to understand the pharmacokinetic behavior of the drug. Results: The presence of strong N-H…Cl intra molecular hydrogen bonding was evidently revealed from the FT-IR spectrum due to the shifting of NH stretching wavenumber. Stability of the molecule arising from hyper conjugative interactions exhibits the bioactivity of the molecule by natural bond orbital analysis. The title molecule binds to the inner pore and blocks voltage - gated sodium channels in peripheral neurons. Conclusion: A detailed molecular picture of DAMP and its interactions were obtained by modeling analysis, IR, Raman, and UV-Vis spectroscopy. The geometrical parameters agree well with the XRD data. NBO analysis indicates the bioactivity of the molecule. The HOMO-LUMO energy gap indicates the possibility of intramolecular charge transfer of the molecule. From the ligand docking studies, it is concluded that the title molecule binds to the inner pore and blocks voltage-gated sodium channels in peripheral neurons.

Background: The drug cinnarizine is used in the treatment of vertigo and migraine. The main drawback is its very low water solubility which causes unpredictable bioavailability. Solubility is better in acidic pH. Therefore, gastro-retentive formulation would be beneficial to improve the bioavailability of the drug. Objective: The objective of the study was to prepare floating microballoons of cinnarizine which would float in the gastric fluid and release the drug in a sustained manner. Methods: Microballoons were prepared by diffusion solvent evaporation technique using polymers (Eudragit® S100, Eudragit® RLPO, Eudragit RL®100), characterised by FTIR, XRD, DSC and optimized by sequential simplex design. For optimization, formulations were graded with respect to formulation efficiency (percentages of yield, sphericity and drug content) and performance index (buoyancy and dissolution efficiency), from which the overall response of the formulations was determined. Finally, the optimized formulation was radiolabelled with 99mTc-MIBI and fed to Wistar albino rats and was evaluated for gastric retention by gamma scintigraphic study. Results: FTIR studies indicated drug and polymers were compatible. DSC and XRD analysis confirmed that the drug was in amorphous state in the formulation. SEM studies confirmed the sphericity of the microballoons. Formulation N7 showed the best overall response (65.61) which was the nearest to the target. Gamma scintigraphic study confirmed that the formulation was retained in the stomach for more than 5 h. Conclusion: The results indicated that floating microballoons of cinnarizine would stay in the stomach for prolonged period and thereby improve the bioavailability of the drug.

Background: Thalassemia Major (TM) is a hereditary disease caused by defective globin synthesis. Because of the significant increase in life expectancy, these patients suffer from various health conditions, including endocrinopathies and low bone mineral density. Aim: The aim of the present study was to evaluate the fracture incidence regarding the markers of bone metabolism, bone mineral density and treatment of osteoporosis as well as the treatment of comorbidities. Methods: Sixty-four patients with TM (32 men and 32 women) participated in a cross-sectional study design. The patients were recruited from “Aghia Sofia” Children’s Hospital and evaluated using Dual-energy X-ray Absorptiometry (DXA) of the lumbar spine and femoral neck and with markers of bone remodeling including Receptor Activator of Nuclear factor Kappa-β Ligand (RANKL), Osteoprotegerin (OPG), C-Terminal Telopeptide (CTX), and sclerostin. Results: The statistical analysis of markers of bone metabolism in relation to fractures revealed no statistical significance. However, statistical analysis of bone mineral density and markers of bone metabolism in relation to fractures was also not significant. Conclusions: In TM patients, fractures are not related to bone mineral density. Maybe some other conditions are the cause, haemosidirosis, drugs, comorbid conditions.

Background: Surgery is the art of treating lesions and malformations of the human body, which involves various surgical techniques. Various classes of drugs are being used in the surgery but unfortunately, the drug utilization pattern of these drugs particularly in developing countries like India, is still unsatisfactory. Thus, there is a need to conduct drug utilization studies of various medicines used in the surgical department. Objective: The main objective of the current study was to evaluate the drug utilization pattern of pre and post-operative medicines used in surgery to promote the rational use of medicines. Materials and Methods: A prospective observational study was carried out over a period of 6 months (November 2017 to April 2018) at Global Hospital, Jalandhar, Punjab, India. A consent form was designed and filled by the patients after explaining the aims and objectives of the study. The Case Record Form (CRF) was designed to collect all the relevant information from the surgery patients. Results: A total of 271 cases have been reported and evaluated. 58.0% of patients were female and 42.0% of patients were male. The most common surgery was nailing, plating and knee replacement. In pre and post-operative procedures, the most common medicines prescribed were a combination of antimicrobials and antacids, followed by anti-emetics and analgesics. Conclusion: The prescribed medicines were less from the National Essential Medical List (EML) which should be increased in the future.

Objective: The present study was designed to evaluate the effects of Atorvastatin (ATO) plus Melatonin (MEL) on streptozocin-induced Diabetic Retinopathy (DR) in rats. Methods: Diabetes was induced in Wistar rats with an intraperitoneal injection of streptozocin (50 mg/kg). Animals were randomly assigned to one of the following groups (8 rats/group): Control group, Diabetic group, Diabetic + MEL group (20 mg/kg/day), Diabetic + ATO group (10 mg/kg/day), Diabetic + MEL + ATO group (as above). Treatments were started one week after induction of diabetes and continued for 7 weeks. At the end of the experiment, angiography was performed and the rats were killed and retinas were harvested for pathological and molecular examinations. Results: Administration of MEL reduced the fluorescein leakage, MDA and ROS levels compared to diabetic group. Treatment with ATO only reduced ROS levels compared to diabetic group. In addition, administration of ATO plus MEL decreased these indices compared to the diabetic and ATO groups. Histologically, retinal vascular congestion was not observed in the combined ATO and MEL group as compared to the diabetic, ATO, and MEL groups. Conclusion: These data provide evidence for the therapeutic value of MEL in combination with ATO in clinical practice for prevention of DR.

Background: The present study assessed the transdermal potential of transferosomes loaded with allopurinol for the treatment of gout. Methods: Transferosomes of allopurinol were composed of different ratios of tween-80, soya lecithin and solvent using a thin-film hydration method. Transferosomes were characterized for Scanning Electron Microscopy (SEM), zeta potential, % entrapment efficiency (%EE), Fourier Transform Infrared Spectroscopy (FTIR), in-vitro drug release and kinetics as well as stability. Then, optimized formulation was incorporated in gel and evaluated for viscosity, pH, extrudability, homogeneity, skin irritation study, spreadability, ex vivo skin permeation study, flux, and stability. Results: SEM studies suggested that vesicles were spherical and zeta potential were in the range of -11.4 mV to -29.6 mV and %EE was 52.4- 83.87%. FTIR study revealed that there was no interaction between allopurinol and excipients during the preparation of transferosomes. The cumulative percentage of drug release from various transferosomes was ranged from 51.87 to 81.87%. A transferosomal gel of F8 formulation was prepared using dispersion method reported pseudoplastic rheological behavior, optimum pH, spreadability and maximum drug permeation i.e. 79.84% with flux 13.06 g/cm2/hr, followed zero-order release kinetics. Irritation and in-vivo studies of optimized transferosomal gel G8 on rabbits revealed better results than the standard allopurinol. Conclusion: This research suggested that allopurinol loaded transferosomal gel can be potentially used as a transdermal drug delivery system for the treatment of gout.

Background: Hypoglycemia may rarely present as hemiparesis and sometimes, it is difficult to differentiate from ischemic stroke. When Random Blood Sugar (RBS) value is between 50 and 70 mg% in patients presenting with focal neurological deficit, no guideline exists to consider the possibility of hypoglycemia before initiating thrombolytic therapy. Clinical Case: A 58-year-old male, with preexisting illness of diabetes and hypertension diabetes and hypertension, was brought to the emergency room with acute onset of right hemiparesis and dysarthria of 90 minutes duration. His NIHSS Score was 9, blood pressure was 150/90 mm of Hg and RBS was 79 mg% on admission. His CT scan brain was normal and was considered for thrombolysis. The resident doctor was not aware of previous sugar repeated RBS before thrombolysis, which was surprisingly 60 mg% 60 minutes after the first RBS. Even though he was a candidate for thrombolysis, intravenous 25% dextrose was administered considering the possibility of hypoglycemia. He made a complete recovery within 20 minutes and thrombolytic therapy was withheld. In diabetic patients with focal neurological deficit and RBS less than 80 mg% on admission, RBS should be rechecked and in appropriate cases, should be challenged with IV dextrose considering the possibility of hypoglycemia before commencing thrombolytic therapy.