Parenteral Route Research Articles

Exploration of Microneedle-assisted skin delivery of cyanocobalamin formulated in ultraflexible lipid vesicles

Vitamin B12 (cyanocobalamin) deficiency is a widespread condition because of its different aetiologies, like malabsorption syndrome or lifestyles as strict veganism that is increasing its incidence and prevalence in developed countries. It has important haematological consequences that require pharmacological treatment. Current therapy consists of oral or parenteral supplements of cyanocobalamin; however, the oral route is discarded for malabsorption syndrome patients and the parenteral route is not well accepted generally. Topical treatments have been suggested as an alternative, but the molecular weight and hydrophilicity of cyanocobalamin limits its diffusion through the skin. Lipid vesicles can allow the transdermal absorption of molecules > 500 Da. The aim of this work was to use different ultraflexible lipid vesicles (transfersomes and ethosomes) to enhance cyanocobalamin transdermal delivery. Vesicles were characterized and lyophilised for long-term stability. The ability to deliver cyanocobalamin through the skin was assessed in vitro using full-thickness porcine skin in Franz diffusion cells. As expected, the best transdermal fluxes were provided by ultraflexible vesicles, in comparison to a drug solution. Moreover, the pre-treatment of the skin with a solid microneedle array boosts the amount of drug that could potentially reach the systemic circulation.

Treatment of hepatitis delta and HIV infection.

Hepatitis delta virus (HDV) is a defective agent that only infects individuals with hepatitis B virus (HBV). Around 5-10% of chronic hepatitis B patients worldwide are superinfected with HDV, which means 15-25 million people. Hepatitis delta is the most severe of all chronic viral hepatitis, leading to cirrhosis, liver cancer and/or transplantation in most patients. Despite it, many HDV patients remain undiagnosed. The only treatment available until recently was peginterferon alfa, with poor results and significant side effects. The recent approval of bulevirtide, a lipopeptide that blocks HBV/HDV entry, has revolutionized the field. Another drug, lonafarnib, already approved to treat progeria, is expected to be available soon as HDV therapy. Since there is no cell reservoir for the HDV RNA genome, hypothetically viral clearance could be achieved if complete blocking of viral replication occurs for a minimum time frame. This is what happens in hepatitis C using direct-acting antivirals, with the achievement of cure in nearly all treated patients. We envision the cure of hepatitis delta using combination antiviral therapy. Given that sexual and parenteral transmission routes are the most frequent for the acquisition of HBV and HDV, shared with HIV infection and HBV/HDV and HIV coinfection. The clinical outcome of hepatitis delta is worst in the HIV setting, with more frequent liver complications. Since most persons infected with HIV are on regular health care follow-up, we propose that HIV-HDV patients should be prioritized for moving forward new and potentially curative treatments for hepatitis delta.

Allergy evaluation of messenger RNA vaccine reactions is crucial, with a specific role for polyethylene glycol testing

Allergy evaluation of messenger RNA vaccine reactions is crucial, with a specific role for polyethylene glycol testing

Reproductive Attitudes and Sexual Behavior of Women and Men Living with HIV

An anonymous survey was conducted, covering the issues of reproductive attitudes and contraceptive behavior in 50 women (mean age of 30.9±4.5 years) and 35 men (mean age of 31.1±3.2 years) with HIV infection of stages 4B and 4C. The study was carried out using a structured questionnaire that included questions about age, marital status, methods of contraception, reproductive plans, and reproductive and medical history. An anonymous interview with 85 HIV-infected respondents revealed that most of the women (82.0%) had contracted HIV through heterosexual contact, while in the men, the parenteral route of HIV infection predominated (57.1%) (P=0.0126). Statistically significant differences were found between the rate of single women and men: 21(42%) women versus 2(5.7%) men (P<0.001). An analysis of contraceptive behavior revealed statistically significant differences: 26% of the women and 8.6% of men (P<0.05) did not use any methods of contraception with regular or irregular sexual life. The majority of respondents used a barrier method of contraception and coitus interruptus. The vast majority of women (80%) had a desire to have children in an indefinite future, as opposed to 37.1% of the men (P<0.001). About 11.4% of men and 10% of women (P>0.05) definitely did not plan pregnancy in the future, mainly because of their unsatisfactory financial situation and the presence of a current HIV infection. Forty-two percent of the women did not undergo periodic medical examinations by a gynecologist or other specialists, and 44% of them indicated the reason for the lack of visits to the doctor as an unsatisfactory attitude of medical personnel towards them. The results obtained are important for the development of optimal medical care that alleviates the burden of HIV infection. In addition to medical care, health care providers must consider social and psychological needs to help HIV patients improve their health, including their sexual and reproductive health.

Phosphate moiety in FDA-approved pharmaceutical salts and prodrugs.

The salification and prodrug approaches modulate the physicochemical properties and absorption, distribution, metabolism, excretion, and toxicity parameters of drugs and lead candidates. The "phosphate" is one of the key counterions/promoiety used in the salt formation and prodrug synthesis. Salification with phosphoric acid enhances the aqueous solubility and thereby facilitates the administration of a drug by the parenteral route. Phosphate moiety in prodrug synthesis mainly improves permeability by lipophilic substitution. Histamine phosphate is the first phosphate salt, and hydrocortisone phosphate was the first prodrug approved by FDA in 1939 and 1952, respectively. The orange book enlists 12 phosphate salts and 17 phosphate prodrugs. Phosphate prodrugs, namely combretastatin A-4 diphosphate, combretastatin A-4 phosphate, lufotrelvir, TP-1287, pyridoxal phosphate, riboflavin phosphate, and psilocybin are clinical candidates. This review focuses on the FDA-approved phosphate salts and prodrugs from 1939 to 2021. The biopharmaceutical advantage of phosphate salts and prodrugs over the parent molecule is also deliberated.

A Concise Review on Skin Disorders

Nowadays, skin disorders are considered very common affecting millions of people worldwide. Ageing, genetic, environmental factors and traumatic injuries are various factors that can lead to several skin disorders. Skin disorders are broadly classified as bacterial, viral, fungal and some other types as well. Some common diagnostic tests relevant for skin disorders include biopsy, scraping, culture, wood light, diascopy and specific skin tests. Medical therapy and physical therapy are the treatment modalities available for skin disorders. Medical therapy includes topical and systemic treatments while physical therapy consists of cryotherapy, phototherapy, photodynamic therapy, lasers and surgery. Topical drugs are the mainstay of treating skin disorders. Systemic drugs are taken directly by oral route or by parenteral route and are distributed throughout the body. The following categories of drugs are divided under topical therapy that includes cleansing agents, protective agents, moisturizing agents, drying agents, anti-itch agents, anti-inflammatory agents, anti-infective agents and keratolytics.

Development of an Effective Nontoxigenic Clostridioides difficile-Based Oral Vaccine against C. difficile Infection.

ABSTRACTThe symptoms of Clostridioides difficile infection (CDI) are largely attributed to two C. difficile toxins, TcdA and TcdB. Significant efforts have been devoted to developing vaccines targeting both toxins through parenteral immunization routes. Recently, we generated a novel chimeric protein (designated Tcd169), comprised of the glucosyltransferase domain (GT), the cysteine protease domain (CPD), and the receptor binding domain (RBD) of TcdB, and the RBD of TcdA. Parenteral immunizations with Tcd169 provide mice effective protection against infection with a ribotype (RT) 027 C. difficile strain. In this study, we expressed Tcd169 in a nontoxigenic C. difficile CCUG37785 strain (designated NTCD), resulting in strain NTCD_Tcd169 to develop an oral vaccine that can target both C. difficile toxins and colonization/adhesion factors. Oral immunizations with NTCD_Tcd169 spores induced systematic and mucosal antibody responses against, not only both toxins, but also C. difficile flagellins (FliC/FliD). Intriguingly yet importantly, anti-Tcd169 sera raised against Tcd169 protein were significantly cross-reactive with FliC/FliD and two surface layer proteins (SlpA and Cwp2). Oral immunizations with NTCD_Tcd169 spores provided mice effective protection against infection with a hypervirulent RT027 C. difficile strain R20291and significantly reduced R20291spore numbers in feces compared with NTCD or PBS immunized mice. These results imply that the genetically modified, nontoxigenic C. difficile strain expressing Tcd169 may represent a novel mucosal vaccine candidate against CDI.IMPORTANCE Clostridioides difficile is an enteric pathogen, and symptoms of C. difficile infection (CDI) are mainly by two exotoxins TcdA and TcdB. Active vaccination is cost-effective approach to prevent CDI and high rates of recurrence. Ideally, vaccines should target both C. difficile toxins and cell/spore colonization. In this study, we expressed immunodominant fragments of TcdA and TcdB (i.e., Tcd169) in a nontoxigenic C. difficile CCUG37785 strain, generating a promising oral/mucosal vaccine candidate against CDI, by targeting both toxins and colonization of pathogenic C. difficile strains. Importantly, anti-Tcd169 sera raised against Tcd169 protein were significantly cross-reactive with FliC/FliD and two surface layer proteins (SlpA and Cwp2), and all of which are involved in C. difficile adhesion/colonization in vitro and in vivo.

Novel drug delivery systems for inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a chronic illness characterized by relapsing inflammation of the intestines. The disorder is stratified according to the severity and is marked by its two main phenotypical representations: Ulcerative colitis and Crohn’s disease. Pathogenesis of the disease is ambiguous and is expected to have interactivity between genetic disposition, environmental factors such as bacterial agents, and dysregulated immune response. Treatment for IBD aims to reduce symptom extent and severity and halt disease progression. The mainstay drugs have been 5-aminosalicylates (5-ASAs), corticosteroids, and immunosuppressive agents. Parenteral, oral and rectal routes are the conventional methods of drug delivery, and among all, oral administration is most widely adopted. However, problems of systematic drug reactions and low specificity in delivering drugs to the inflamed sites have emerged with these regular routes of delivery. Novel drug delivery systems have been introduced to overcome several therapeutic obstacles and for localized drug delivery to target tissues. Enteric-coated microneedle pills, various nano-drug delivery techniques, prodrug systems, lipid-based vesicular systems, hybrid drug delivery systems, and biologic drug delivery systems constitute some of these novel methods. Microneedles are painless, they dislodge their content at the affected site, and their release can be prolonged. Recombinant bacteria such as genetically engineered Lactococcus Lactis and eukaryotic cells, including GM immune cells and red blood cells as nanoparticle carriers, can be plausible delivery methods when evaluating biologic systems. Nano-particle drug delivery systems consisting of various techniques are also employed as nanoparticles can penetrate through inflamed regions and adhere to the thick mucus of the diseased site. Prodrug systems such as 5-ASAs formulations or their derivatives are effective in reducing colonic damage. Liposomes can be modified with both hydrophilic and lipophilic particles and act as lipid-based vesicular systems, while hybrid drug delivery systems containing an internal nanoparticle section for loading drugs are potential routes too. Leukosomes are also considered as possible carrier systems, and results from mouse models have revealed that they control anti- and pro-inflammatory molecules.

Lornoxicam-Loaded Chitosan-Decorated Nanoemulsion: Preparation and In Vitro Evaluation for Enhanced Transdermal Delivery.

Nanoemulsions are promising drug delivery systems for the administration of poorly soluble drugs like lornoxicam (LRX) by oral or parenteral routes. Such formulations work perfectly for transdermal delivery of lornoxicam-type drugs. It has also been established that formulating such a delivery system is highly dependent on the presence, type, and concentration of excipients taking part in the formulation. The inherent characteristics of nanoemulsion (NE), i.e., smaller globule size and excipient nature, facilitate the drug’s passage through skin. The current study was aimed at the development of an NE-based formulation of LRX to improve the drug solubility in vitro as well as to enhance drug skin permeation to promote therapeutic outcome in appropriate time. Spontaneous self-emulsification technique was utilized to develop optimized LRX-encapsulated NE-based formulations. ATR-FTIR spectra of the pure drug and various formulations did not show any interaction between the drug and various formulation excipients showing compatibility. Globule size for stable formulations ranged between 63–168 nm. These formulations were characterized for viscosity, surface tension, pH, drug encapsulation efficiency, in vitro drug release, and drug skin permeation studies. Chitosan-decorated optimized NE formulation of LRX showed about 58.82% cumulative drug release, showing an anomalous non-Fickian diffusion mechanism of drug release. Drug encapsulation efficiency, in vitro drug release, and skin permeation studies exhibited promising results. An appreciable drug entrapment efficiency was exhibited by optimized NE formulations LRX-6, 71.91 ± 3.17% and C-LRX, 65.25 ± 4.89%. Permeability parameters like enhancement ratio (Er), permeability constant (Kp), and steady state flux (Jss) showed higher values and exhibited good results based on formulation type. The selected promising formulation type “LRX-6” showed significantly different results as compared to other formulations (LRX-4, 5, and 7). The skin permeation property of the LRX-6 formulation was compared to similar chitosan-based formulations and was found to have better skin permeation results than chitosan-based formulations. This study clearly exhibited that an LRX-containing NE-based formulation can be formulated to form a stable drug delivery system. Such formulations are promising in terms of physicochemical characteristics, improved solubility, and high skin permeation potential.

A Study on Prescription Pattern and Assessment of Smoking as a Risk Factor among COPD Patients in a Tertiary Care Hospital

Abstract: Aim: The aim is to study the prescription pattern and to assess whether smoking is a major risk factor among COPD patients in a tertiary care hospital. Materials and Methods: A prospective observational study was conducted for 6 months. All the data were collected, documented and analysed based on standard protocol. Data collected were entered and statistically analysed using Microsoft Excel. Results: 120 patients (83 male and 37 female) were included in the study. COPD was more common in the age group of 61-70 years with an average age of 66.8 years. Hypertension ((38.33%) was the most common comorbidity followed by diabetes mellitus. Smoking (66.6%) was a major risk factor followed by indoor pollution (16.60%) outdoor pollution, family history and asthma respectively. Among smokers, 61.25% were ex-smokers. 46.25% of smoking patients had pack years of 11-20. Most commonly prescribed drugs were Bronchodilators (98.30%), antibiotics (85.80%) and corticosteroids (70%). Deriphylline was the most commonly prescribed bronchodilator. Beta lactam antibiotics were most commonly prescribed antibiotics. Among other drugs, GI drugs were commonly prescribed. Parenteral route was mostly preferred, followed by inhalation and oral respectively. Conclusion: The study provides insight into the prescription pattern and shows that smoking is a major risk factor among COPD patients. In this study, bronchodilators were the most commonly used drug followed by antibiotics and corticosteroids. Smoking is a major risk factor followed by indoor pollution, outdoor pollution, family history and asthma respectively. Keywords: Chronic obstructive pulmonary disease, Comorbidities, Prescription pattern, Smoking, Risk factors.

Formulation of Amphotericin B in PEGylated Liposomes for Improved Treatment of Cutaneous Leishmaniasis by Parenteral and Oral Routes.

Liposomal amphotericin B (AmB) or AmBisome® is the most effective and safe therapeutic agent for visceral leishmaniasis (VL), but its clinical efficacy is limited in cutaneous leishmaniasis (CL) and HIV/VL co-infection. The aim of this work was to develop a formulation of AmB in PEGylated liposomes and compare its efficacy to AmBisome® in a murine model of CL. Formulations of AmB in conventional and PEGylated liposomes were characterized for particle size and morphology, drug encapsulation efficiency and aggregation state. Those were compared to AmBisome® in Leishmania amazonensis-infected BALB/c mice for their effects on the lesion size growth and parasite load. The conventional and PEGylated formulations showed vesicles with 100–130 nm diameter and low polydispersity, incorporating more than 95% of AmB under the non-aggregated form. Following parenteral administration in the murine model of CL, the PEGylated formulation of AmB significantly reduced the lesion size growth and parasite load, in comparison to control groups, in contrast to conventional liposomal AmB. The PEGylated formulation of AmB was also effective when given by oral route on a 2-day regimen. This work reports for the first time that PEGylated liposomal AmB can improve the treatment of experimental cutaneous leishmaniasis by both parenteral and oral routes.

Parenteral vaccination strategies target protective immunity to the small and large intestine mucosa

Abstract Prophylactic vaccines are most commonly given by a parenteral route. However, this strategy often confers poor protection against GI pathogens because antigens are primarily presented in peripheral lymph nodes, which do not provide the prerequisite ‘tissue imprinting signals’ to target memory T and B cells to the gut. Here, we describe a platform that enables parenteral vaccines to target protection to the GI tract. This was achieved by subcutaneous (s.c.) delivery of compounds known to imprint gut tropism onto lymphocytes. Am80, a retinoic acid receptor agonist, targeted immunity to the small intestine through up-regulation of gut-homing receptors α4β7 and CCR9, and promotion of IgA class-switching. S.c. injection of OVA + CpG combined with repeated injections of Am80 generated significantly higher and durable fecal anti-OVA IgA titers, compared to OVA + CpG without Am80. Vaccination with Am80 also increased antigen-specific CD4 and CD8 T cell trafficking to the small intestine and generated tissue resident memory T (Trm) cells. To overcome the need for multiple doses of Am80, which can cause tissue toxicity at the injection site and hinder clinical translation, we developed a polymeric nanocarrier that showed equivalent imprinting efficacy upon a single injection, lowering the cumulative dose to one-third. Furthermore, we also developed a modified vaccination strategy that could augment effector and memory T cell responses not only in the small intestine, but also in the cecum, colon and rectum, conferring protection to the entire intestinal tract. We conclude that supplementation with mucosal imprinting signals is a promising approach to enhance parenteral vaccines by generating mucosal protection against GI infections. Supported by the Bill & Melinda Gates Foundation

Metabolic Bone Disease of Prematurity.

Metabolic Bone Disease of Prematurity.

Comparison of the Safety and Efficacy of Tofacitinib and Fingolimod in TNBS‐Induced Colitis Model in Adult Zebrafish: The Role of Myd88/NF‐κB/TNF‐α Signaling Pathway

Due to the inadequate response, side effects, parenteral route of administration, and immunogenicity, oral targeted small molecules seem to replace monoclonal antibodies in the future management of ulcerative colitis (UC). In order to pave the way for clinical translations of small molecules in UC, for the first time, we compared the efficacy of fingolimod and tofacitinib in preclinical model of colitis, and uncovered another mechanism of action that these medicines may act through.We implicated adult zebrafish to find out its pros/cons, investigated aquatic toxicity of the mentioned compounds, and designed a procedure to evaluate compound's efficacy in adult zebrafish colitis model; hence, facilitating screening of further agents.Tofacitinib and fingolimod were investigated to be in category 1 of Globally Harmonized System (GHS) aquatic toxicity classification with the LC50 of 0.9014 and 0.36 mg/L, respectively, based on the acute toxicity assessment within 96 h.Considering efficacy assessments, colitis was induced through intrarectal administration of 160 mM TNBS for 48 h. Then, animals were exposed to different concentrations of tofacitinib (0.25, 0.57, 0.72, 0.90 mg/L) and fingolimod (0.23, 0.28, 0.36, 0.45 mg/L) for 96 h. Subsequent analyses revealed that TNBS significantly reduced length of villi, number of goblet cells, level of TNF‐α, MyD88, and NF‐κB2, increased thickness of villi and necrosis, and induced histopathological changes, including intestinal edema, submucosal hemorrhage/hyperemia with the presence of inflammatory cells. All the aforementioned parameters were considerably enhanced almost dose‐dependently with both agents, wherein the effect of 0.45 mg/L fingolimod was superior to other groups. As well, there were no signs of hyperemia/hemorrhage in harvested intestinal samples. Resultantly, we revealed that these medications may suppress canonical and non‐canonical NF‐κB pathways through targeting toll‐like receptors and MyD88.Given the better efficacy and multi‐targeted action of fingolimod, it worth to focus on sphingosine‐1 phosphate receptor modulators in clinical trials of UC and compare them with other classes of medications; albeit, their ecotoxicity aspect should not be overlooked.

Review on Orodispersible Tablet: Recent Trends of Manufacturing of Orodispersible Tablet

The article mainly focuses on several aspects of orodispersible tablets (ODTs). These types of tablets are those when placed in the mouth cavity disperse the drug in very rapid manner i.e. instantaneously releasing the drug which dissolve in saliva. ODTs are alternative dosage forms for the patients who are suffering from dysphasia i.e. difficulty in swallowing. The oral administration of the drug is most important method for administrating the drugs for systemic effects. Except that the parenteral route is not used routinely for self-administration e.g. insulin. The topical route is only applicable to deliver the drugs into the body for the systemic effect. The administration of the drug by the parenteral route is only beneficial for treating medical emergencies in which the subject is comatose or can’t swallow. Never the less it is probable that at least 90% of all drugs used to provide systemic effects are administered by the oral route. ODTs are different from traditional tablets in that they are designed to be dispersed on the tongue rather than swallowed whole. ODTs dissolve or disintegrate in the oral cavity without the need of water or chewing. And also it is mainly used for rapid action, to enhance the bioavailability, accurate dosing, enhance palatability, ease of administration, accurate dosing, having good patient compliance because most of the people are familiar with this route. Drugs present in ODTs do not suffer from the first-pass metabolism. This type of drug administration or delivery is becoming popular day by day due to its numerous advantages.

AUTOMATION OF DRUG DISPENSING: FEEDBACK FROM A HOSPITAL PHARMACY

Background: Ensuring drug circuit security is the ultimate goal for hospital pharmacists. Alarmed by the excessive drug consumption at its on-duty pharmacy, Mohammed V Military Teaching Hospital of Rabat (Morocco) installed a centralized automation for drugs dispensation. This experience is expected to be decentralized to all care units. Our study purpose is to evaluate automations impact on pharmaceutical drug management, and then to determine limits to be improved. Resources and procedures: We analyzed, over a period of 10 months, data from the database of the automated distribution system deposited at our on-duty pharmacyin order to determine its usage profile. We also evaluated through a questionnaire the point of view of our 13 pharmacy technicians toward drug dispensing automation. Results: Over the study period, we got the following results: - 5446 transactions were accomplished and 8864 drugs unit were dispensed - Parenteral route drugs are the most delivered (67%) - Anti-inflammatories and analgesics are the most required (26%), followed by the anti-infective drugs (25%) - Young technicians did more transactions (63%) than the elders did (37%) - According to pharmacy technicians, main automations advantages are saving time in locating medications (8/13) and limiting drugs errors (5/13). Otherwise, main constraints are the irregular machine replenishment (10/13) and the reduced capacity for storing all medications (6/13), specially refrigerated and oversized ones. Conclusion: Automation of drug delivery offers many advantages. However, there are still limits to be improved before its decentralization to all care units.

Evaluation of Intranasal Midazolam for Pediatric Sedation during the Suturing of Traumatic Lacerations: A Systematic Review.

Objective: The objective of this study was to evaluate the efficacy and safety of intranasal midazolam as part of a paediatric sedation and analgesic procedure during the suturing of traumatic lacerations in paediatric emergency departments. Methodology: A systematic review of clinical trials was completed in July 2021. The databases consulted were PUBMED, SCOPUS, WEB OF SCIENCE, NICE and Virtual Health Library. Eligibility criteria: randomised and nonrandomised clinical trials. Two independent, blinded reviewers performed the selection and data extraction. The participants were 746 children, of whom, 377 received intranasal midazolam. All of the children were admitted to an emergency department for traumatic lacerations that required suturing. The quality of the articles was evaluated with the Jadad scale. This systematic review was conducted according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Results: Nine studies were included in the review. The intranasal administration of midazolam in healthy children produces anxiolysis and minimal/moderate sedation without serious side effects. Although there are combinations of parenteral drugs that produce deeper sedation, they also have greater adverse effects. No significant differences in the initiation of sedation and the suture procedure were found between the intranasal route and the parenteral route. Conclusions: The use of intranasal midazolam in healthy children produces sufficiently intense and long-lasting sedation to allow for the suturing of traumatic lacerations that do not present other complications; therefore, this drug can be used effectively in paediatric emergency departments.

An Overview on Nano Niosomes: As an Optimistic Drug Delivery System in Targeted Drug Delivery

Targeted drug-delivery systems are used for the administration of pharmaceutical medicament enables the localization of drugs to diseased sites. Different types of drug-delivery systems uses carriers, like immunoglobulins, serum proteins, synthetic polymers, liposomes, nanoparticle and microspheres. Niosomes are an emerging type of novel vesicular systems. Now they are being fervent explored as potential carriers for targeted drug delivery. In addition to conventional, oral, and parenteral routes, they are liable to be delivered by ocular, transdermal, vaginal, and inhalation routes. Nano-niosomes are non-ionic surfactants based vesicles that are biodegradable, relatively nontoxic, more stable and inexpensive than liposomes. Other component, such as cholesterol, can be used to give the rigidity to the niosomes structure. The unique vesicular structure of niosomes, with their bilayer lamellae assembled by nonionic surfactants, is able to increase the bioavailability of a drug to a predetermined area for a period. The amphiphilic nature of niosomes promotes their efficiency in encapsulating hydrophobic or hydrophilic drugs. These nonionic vesicular carriers not only transport the pharmacological agents to target site or disease site, avoiding normal tissues and reducing toxicity in the rest of the body, but also protect drugs from degradation, increase the half-life, payload and solubility of drug and reduce renal clearance. This present review describe overview of niosomes formulation aspects, structure, types of niosomes, advantages, and disadvantages, method of preparation as well as some general observations on niosomes.

A nanoemulsion based transdermal delivery of insulin: Formulation development, optimization, in-vitro permeation across Strat-M® membrane and its pharmacokinetic/pharmacodynamic evaluation

Peptides and proteins are mainly delivered through the parenteral route which is painful and reduces patient compliance. The aim was to explore the feasibility of using nanoemulsion as an alternative carrier for the transdermal delivery of insulin. For this purpose, pseudoternary phase diagram was constructed to determine the exact ratio of nanoemulsion components. A Simplex lattice design was used to formulate nanoemulsion comprising of oleic acid, tween 80, isopropyl alcohol, and water as independent variables and droplet size, entrapment ratio, and flux as responses. Particle size distribution was determined through DLS and SEM. The gradient-HPLC method for the quantification of insulin was developed and validated. The in vitro permeation was carried out using Strat-M® membrane. Circular dichroism (CD), native gel electrophoresis, storage stability at 4 °C, skin irritation, pharmacokinetics, and pharmacodynamic study of optimized nanoemulsion were also performed. Optimized formulation was based on the small droplet size (41.05 ± 8 nm), maximum entrapment ratio (93.08%), and higher flux of (1.75 μg/cm2/h). The developed chromatographic method detected insulin in the range of 0.5–2.4 μg/mL. The CD spectra revealed minor changes in the secondary structure of insulin due to the entrapment in the micelles of nanoemulsion. The optimized nanoemulsion formulation was stable for three months. The PK/PD analysis indicated the slow absorption of insulin from the nanoemulsion as compared to SC injection in Albino Wister rats, resulting in delayed and consistent response having relative bioavailability of 244.5%. The results indicate that this system may be a promising vehicle for transdermal insulin delivery.

Use of parenteral methotrexate in rheumatic diseases: A systematic review

ObjectiveTo analyse the efficacy, adherence, patient satisfaction, safety, pharmacodynamics and cost-effectiveness of parenteral methotrexate (MTX) in patients with rheumatic diseases. MethodsA systematic review of literature was carried out in Medline, Embase and Cochrane Central from the beginning until June 2019. Studies including adult patients with rheumatic diseases being treated with parenteral MTX were identified and data on efficacy, adherence, satisfaction, safety, pharmacokinetics, and cost-effectiveness analysed. As for the designs, systematic reviews, clinical trials, or observational studies were permitted, including cross-sectional and small-sample studies if they were pharmacokinetic studies. ResultsOut of 4160 identified articles, 80 articles were finally included. The efficacy profile of parenteral MTX seems useful in general and in those patients with insufficient response to oral MTX. The parenteral route does not seem to increase the rate or severity of adverse events due to the use of MTX. The use of parenteral MTX is an appropriate way to reduce costs in patients with inadequate response to oral MTX. Adherence and satisfaction are favoured by training programmes in the use of the parenteral route. The results in rheumatic diseases other than rheumatoid arthritis (RA) are very scarce and do not enable obtaining conclusive data. ConclusionsParenteral MTX can be an alternative to the use of oral MTX, due to its profile of efficacy, safety, adherence and pharmacoeconomic results, especially in those patients with RA.