Reduced Dosing Frequency Research Articles

Transdermal Drug Delivery System: An Overview

From the past three decades there are huge changes and developments in formulation technology. Innovations in drug delivery systems are not only associated with the development of novel dosage forms but also with the development of new formulations using existing drugs for the treatment. These innovations in delivery of drug have many advantages like better patient compliance, maintenance of steady state concentration of drug for the prolong period, reducing dosing frequency, drug targeting to desired site of action and low side effects. TDDS are designed for delivery of drugs across the skin and it provides both controlled and continuous administration drug. It terminates the pulsed entry of drug in systemic circulation due to which side effects are observed. This transdermal route of drug delivery has more benefits and convenience than oral route and enhances the safety and efficacy of drug; it is patient friendly and painless device that provides regulated, uniform administration and the continuous supply of drug to targeted site for treatment of various diseases.

DEVELOPMENT EVALUATION AND CHARACTERIZATION OF BUCCAL PATCHES CONTAINING ATENOLOL USING HYDROPHILIC POLYMERS

Objective: The present investigation focused on fabrication and evaluation of atenolol releasing buccal patches comprising mucoadhesive hydrophilic polymers like sodium alginate and tamarind seed polysaccharide with a drug-free backing layer (6 % ethylcellulose). Methods: Solvent evaporation technique being employed in the development of atenolol comprising buccal patches using mucoadhesive hydrophilic polymers. The prepared buccal patch formulations were tested for thickness, weight variation, folding endurance, drug content, moisture content, moisture absorption, % swelling, surface pH, in vitro residence time and mucoadhesion studies. The drug permeation through goat buccal mucosal membrane was conducted with the use of Franz diffusion cell in phosphate buffer saline, pH 6.8 and was subjected to FT-IR and SEM characterization. Stability study was performed as per ICH guidelines. Results: For all the buccal patch formulations, the average weight, thickness, drug content, moisture content, moisture absorption, % swelling, surface pH study exhibited satisfactory results. Out of 7 different buccal patches, the formulation FA-1 revealed the highest mucoadhesive strength (31.36±0.95 g), the force of adhesion (0.31±0.04 N), maximum swelling index (341±0.83 %) and more than 24 h in vitro residence time. The buccal patch formulation FA-1 indicated highest drug permeation (97.51 %) in 24 h and was found to be stable. FT-IR examination confirms lack of drug polymer interaction. SEM investigation reveals a smooth surface of the buccal patch. Conclusion: The developed buccal patches comprising atenolol can be very promising in increasing patient compliance and reducing dosing frequency.

Development and pharmacokinetic evaluation of osmotically controlled drug delivery system of Valganciclovir HCl for potential application in the treatment of CMV retinitis.

Valganciclovir HCl (VGH) is the widely used drug for the treatment of cytomegalovirus (CMV) retinitis infection with an induction dose of 900mg per oral (p.o.) twice a day and a maintenance dose of 900mg (p.o.). This required dose of the drug also leads to multiple side effects due to repeated administration. The research was highlighted to develop, formulate, optimize, and evaluate single-core osmotic pump (SCOP) tablet of VGH with the dose of 450mg to reduce dosing frequency and associated side effects. The decrease in dose also minimizes the hepatic and nephrotic load. The optimized batch of the formulation was subjected to comparative in vitro and in vivo evaluation. The tablet core composition is the primary influencer of the drug delivery fraction in a zero order, whereas the membrane characteristics control the drug release rate. In vivo pharmacokinetic studies revealed that the newly developed osmotic formulation has controlled zero-order release for 24h with a single dose of 450mg while the marketed formulation requires twice administration within 24h to maintain the plasma concentration in the therapeutic window. The pharmacokinetic study demonstrated that the developed formulation has the area under curve (AUC) of 58.415µgh/ml with single dose while the marketed formulation shows the AUC of about 37.903µgh/ml and 31.983µgh/ml for first and second dose, respectively. The large AUC demonstrates the extended release of drug with a single dose and effective plasma concentration. Hence, the developed formulation can be a promising option for the treatment of CMV retinitis with the minimum dose and dosing frequency.

Advanced nitrogen removal in a single return anaerobic/aerobic/anoxic/aerobic (AnOAO) bioreactor treating municipal wastewater through hydroxylamine addition: Performance and microbial community

The NH2OH dosing strategy for nitrogen removal was investigated in a single return continuous-flow anaerobic/aerobic/anoxic/aerobic (AnOAO) reactor fed with real municipal wastewater. A high nitrite accumulation ratio of 98% was achieved in only two days by continuously adding 10 mg/L NH2OH. When gradually reducing dosing frequency to one day every four days, effluent total nitrogen was as low as 4.8 ± 2.2 mg N/L with removal efficiency of 88.7 ± 5.3%, under aerobic HRT of 4.6 h, DO below 1.0 mg/L, and C/N of 2.8 without external carbon sources. Batch test showed that nitrite oxidizing bacteria (NOB) activity decreased by 81% after adding NH2OH, while ammonia oxidizing bacteria (AOB) activity remained stable. qPCR confirmed that NOB abundance decreased, and 16S rRNA sequencing further showed that g_Nitrospira belonging to NOB decreased significantly (P < 0.001). Overall, this study provides a novel strategy for advanced nitrogen removal from municipal wastewater in continuous flow systems.

FABRICATION, OPTIMIZATION AND EX-VIVO CHARACTERIZATION OF FEBUXOSTAT LOADED NANOSTRUCTURED LIPID CARRIER BY 3 SQUARE FULL FACTORIAL DESIGN

Nano Structured Lipid Carriers (NLCs) are potential alternative of the tradition colloidal drug carrier. The main benefit is related to the well-known concept that lipids used in nanoparticle formulation promote drug oral absorption because they go through the same physiological mechanism as food lipid digestion. The objective of the present work is to use potential carrier NLCs for the oral delivery of poorly soluble drug Febuxostat (FEB). FEB-NLCs were formulated by High Speed Homogenization with Ultra sonication method using Capmul GMS 50 K as solid lipid and Transcutol HP as a liquid lipid. The 32 full factorial design utilized to study the effect of influence of solid lipid to liquid lipid ratio and concentration of surfactant, on the particle size and entrapment efficiency. Mean particle size and entrapment efficiency were found for all prepared formulation in the range of 196.66±2.08 nm to 368.33±2.51 nm and 74.80±0.52 % to 86.47±0.749 % respectively. Zeta potential was -15.2mv which is negative enough to give good stability. TEM study shows good spherical morphology of particle with diameter less than 200nm. In-vitro and Ex-Vivo study revel that NLCs gives biphasic release of the drug; first initial burst release and then sustained release up to 24 hour. The formulated NLCs dispersion was successfully converted in to the free flowing powder using trehalose as a cryoprotectant. In conclusion, FEB-NLCs potential carrier for the oral delivery and controlled release of drug which may reduce dosing frequency and improve patient compliance.

Longer Duration Of Peanut Oral Immunotherapy At A Reduced Dosing Frequency Increases The Rate Of Sustained Unresponsiveness Without Reducing Clinical Efficacy

There are limited published data as to the impact of longer duration of peanut oral immunotherapy (OIT) on desensitisation and sustained unresponsiveness (SU). We evaluated symptom thresholds and SU (after stopping OIT for one month) in peanut-allergic individuals undergoing up to 3 years of peanut OIT.

A nanoparticulate dual scavenger for targeted therapy of inflammatory bowel disease.

A therapeutic strategy that targets multiple proinflammatory factors in inflammatory bowel disease (IBD) with minimal systemic side effects would be attractive. Here, we develop a drug-free, biodegradable nanomedicine that acts against IBD by scavenging proinflammatory cell-free DNA (cfDNA) and reactive oxygen species (ROS). Polyethylenimine (PEI) was conjugated to antioxidative diselenide-bridged mesoporous organosilica nanoparticles (MONs) to formulate nanoparticles (MON-PEI) that exhibited high cfDNA binding affinity and ROS-responsive degradation. In ulcerative colitis and Crohn’s disease mouse colitis models, orally administered MON-PEI accumulated preferentially in the inflamed colon and attenuated colonic and peritoneal inflammation by alleviating cfDNA- and ROS-mediated inflammatory responses, allowing a reduced dose frequency and ameliorating colitis even after delayed treatment. This work suggests a new nanomedicine strategy for IBD treatment.

Ocular Delivery of Atenolol Loaded Microsponge in-situ Gel: Development, Characterization and in-vitro Evaluation

Abstract: Aim/Background: The purpose of the study was to fabricate and evaluate atenolol loaded micro-sponge in-situ gel. Materials and Methods: Oil in Oil Emulsion Solvent Diffusion Technique was used for formulation of microsponges by using different levels of polymers such as Eudragit RS-100 and Ethyl Cellulose. The prepared micro-sponges were evaluated for optical microscopy, percentage yield, drug content, entrapment efficiency and surface morphology studies. The micro sponges were loaded into in-situ gel. The gel was characterized for pH, rheological behavior, in vitro gelling capacity and in vitro drug release study. Results: The smicrosponges were found in the size range of 7.43 to 9.26μm. The formulation F1 has smallest particle size while F9 has largest size. The product yield varies from 66.98% to 89.87 %.The drug content was found to be maximum for formulation F8 which is 94.19%. Similarly, the entrapment efficiency was found maximum for formulation F8 which is 93.89%. The gel was characterized for pH. The pH of drug loaded microsponge gel were found in range of 7.43±0.27 to 9.26±0.61.Similarly, viscosity ranges from 32 to 39 cps. The data of in-vitro release shows that 60.12% drug was released up to 24hr. Conclusion: The mirosponges laden in situ gel was effectively prepared by oil in oil emulsion solvent diffusion method (O/O ESDM). Further, the formulation will provide benefits in terms of sustained/controlled release, reduces dosing frequency and provides better compliance to the patient. Key words: Microsponge, Atenolol, Ethyl Cellulose, Eudragit RS-100, in situ gel.

Preparation of Losartan Potassium Controlled Release Matrices and In-Vitro Investigation Using Rate Controlling Agents.

Controlled release matrices have predictable drug release kinetics, provide drugs for an extended period of time, and reduce dosing frequency with improved patient compliance as compared with conventional tablet dosage forms. In the current research work, losartan potassium controlled release matrix tablets were fabricated and prepared with rate altering agents; that is, Ethocel grade 100 combined with Carbopol 934PNF. Various drug to polymer ratios were used. HPMC, CMC, and starch were incorporated in some of the matrices by replacing some amount of filler (5%). The direct compression method was adopted for the preparation of matrices. In phosphate buffer (pH 6.8), the dissolution study was conducted by adopting the USP method-I as the specified method. Drug release kinetics was determined and dissolution profiles were also compared with the reference standard. Prolonged release was observed for all matrices, but those with Ethocel 100FP Premium showed more extended release. The co-excipient (HPMC, CMC, and starch) exhibited enhancement in the drug release rates, while all controlled release matrices released the drug by anamolous non-Fickian diffusion mechanism. This combination of polymers (Ethocel grade 100 with Carbopol 934PNF) efficiently extended the drug release rates up to 24 h. It is suggested that these matrix tablets can be given in once a day dosage, which might improve patient compliance, and the polymeric blend of Ethocel grade 100 with Carbopol 934PNF might be used in the development of prolonged release matrices of other water-soluble drugs.

Fabrication and Evaluation of Gemcitabine-loaded Alginate Microspheres: A Potential Approach for Treatment of Various Carcinomas

Abstract: Aim/background: Microspheres are spherical particles, having a core, having a particle size of 1μm to 1000μm. They are advantageous as compared to conventional dosage forms of drugs, in parameters like sustainability and control of drug release, drug protection, biodegradability, targeting ability and many more. Gemcitabine is a prodrug and is used in various carcinomas. Sodium Alginate and Ethyl Cellulose are used as polymers. The fabrication aims to sustain the drug release which can treat pancreatic, breast, ovarian and lung cancer. Materials and Methods: Microspheres have been made by Ionotropic Gelation method, Sodium alginate, Ethyl cellulose and Calcium chloride. Weighed quantity of drug and polymer were added to sodium alginate solution, which was then added drop wise to Calcium chloride solution under continuous stirring to procure spherical rigid microspheres. These were then subjected to various physicochemical characterizations and surface analysis. Results and Conclusion: Results have shown that by increasing the polymer concentration, entrapment efficiency and drug loading have also increased. Particle size, SEM and micromeritic evaluation have exhibited satisfactory results. The drug release studies depict that most of the batches have showed less than 10% release acid media so it protects the drug from the upper part of GI Tract. These attributes prove that microsphere technology, being a crucial novel drug delivery system can be very effective in reducing dose frequency, dose dumping and better patient compliance. Key words: Gelation, Targeting, Sustainability, Microspheres, Entrapment Efficiency.

POSA380 Qualitative Development of Surveys to Assess Real-World Patient and Caregiver Perspectives of Atypical Hemolytic Uremic Syndrome Treatment Preferences and Impact

Eculizumab and ravulizumab are complement C5 inhibitors approved for atypical hemolytic uremic syndrome (aHUS). Ravulizumab was engineered from eculizumab to reduce dosing frequency (every 4 or 8 weeks [bodyweight dependent] vs every 2 weeks [patients >10kg], respectively). The impact of less frequent administration on patients with aHUS and their treatment preferences has not been studied.

FORMULATION AND DEVELOPMENT OF NOVEL GASTRORETENTIVE MICROBALLOONS OF REPAGLINIDE

The present study involves preparation and evaluation of Microballoons of Repaglinide which is having poor solubility in water and low oral bioavailability. Repaglinide, an oral hypoglycemic agent, is rapidly absorbed and eliminated from the body after oral administration. The peak plasma level occurs within an hour of oral administration with elimination half life of 1 hr. The objective of the present work is to prepare floating microballoons of Repaglinide for delivering the drug in controlled manner which will help to reduce dosing frequency and maintain the plasma concentration of drug for longer time without fluctuations. This will be helpful in having better control over clinical maintenance of the type 2 diabetic condition. The Microballoons were prepared by solvent evaporation emulsification technique using Sodium Alginate as coating agent and Calcium Chloride as cross-linking agent. The formation of spherical and hollow Microballoons was confirmed by SEM studies ranging from 220 to 310 μm. The percentage of drug entrapment was found to be 70-80%. The Micromeritic properties indicated better flowability of the spheres. The Buoyancy test showed good floatability for more than 12 hrs. Formulation B5, C5 and D3 showed higher buoyant percentage after 12 hours and percentage yield. Microballoons of Repaglinide were designed to increase the Solubility, Bioavliability and to improve the patient compliance. The microballoons with the smaller particle size enhanced the in vitro drug release of the Repaglinide. Thus, microballoons approach may be a promising carrier for Repaglinide and other BCS class II drugs.

Comparative efficacy of ravulizumab and eculizumab in the treatment of atypical hemolytic uremic syndrome: An indirect comparison using clinical trial data.

Ravulizumab and eculizumab are approved terminal complement inhibitor treatments for atypical hemolytic uremic syndrome (aHUS). Ravulizumab was engineered from eculizumab to have an increased half-life allowing for reduced dosing frequency (8-weekly vs. 2-weekly). To account for differences in respective clinical trials, a validated balancing technique was used to enable an indirect comparison of ravulizumab and eculizumab treatment efficacy in aHUS. Patient-level data from four eculizumab clinical trials were available for pooling and comparison with data from two ravulizumab trials. In the primary analysis, adult native kidney data were compared. Propensity scores were calculated from baseline characteristics (dialysis status, estimated glomerular filtration rate, platelet count, serum lactate dehydrogenase). Stabilized inverse probability weighting was used to balance groups. Changes in outcomes from baseline to 26 weeks were compared between treatment groups. Sensitivity and subgroup analyses were conducted to assess the robustness of findings. Overall, 85 patients (46 ravulizumab, 39 eculizumab) were included in the primary analysis. Demographic and clinical characteristics were well balanced after weighting at baseline. At 26 weeks, clinical outcomes (including renal function, hematological markers, and dialysis prevalence), and fatigue and quality of life measures were improved with eculizumab and ravulizumab treatment. No differences between treatment groups reached statistical significance, although confidence intervals were wide. Sensitivity and subgroup analysis results were consistent with those of the primary analysis. Using appropriate methodology for indirect comparison of studies, no differences in outcomes were seen between ravulizumab and eculizumab, although, owing to small sample sizes, confidence intervals were wide.

Dose Uniformity of Loteprednol Etabonate (Submicron) Ophthalmic Gel 0.38% Compared with Prednisolone Acetate Ophthalmic Suspension 1.

IntroductionLoteprednol etabonate (submicron) ophthalmic gel 0.38% (LE SM gel 0.38%) is a corticosteroid formulation designed to retain the nonsettling characteristics of loteprednol etabonate ophthalmic gel 0.5%, but with reduced drug particle size to improve ocular penetration, allowing for reduced dosing frequency. This study compared the dose uniformity of LE SM gel 0.38% with branded and generic prednisolone acetate (PA) 1% suspensions under simulated in-use dosing conditions.MethodsDrug concentrations in drops of LE SM gel 0.38% and PA 1% suspensions, expressed from bottles that were shaken or not shaken, were determined during 2 weeks of simulated on-label dosing (LE SM gel 0.38%: three times daily; PA suspensions: four times daily). Sedimentation of drug particles was assessed for each product using dispersion analysis.ResultsThe mean (SD) percent declared drug concentration of LE SM gel 0.38% over 2 weeks was 103.2% (1.3%) when the drug was dispensed from shaken bottles and 103.3% (1.5%) when dispensed from unshaken bottles. However, for branded and generic PA suspensions, mean (SD) percent declared concentrations were 102.2% (1.4%) and 98.3% (2.9%), respectively, when dispensed from shaken bottles; and 89.2% (18.6%) and 78.3% (13.5%), respectively, when dispensed from unshaken bottles. Dispersion analysis showed that drug particles in LE SM gel 0.38% remained fully suspended under accelerated sedimentation conditions, whereas both branded and generic PA suspension drug particles settled out of suspension.ConclusionsLE SM gel 0.38% delivered the drug consistently at the declared concentration over the entire 2 weeks of simulated in-use dosing conditions, regardless of whether the drug was dispensed from shaken or unshaken bottles. However, both branded and generic PA suspensions required the bottle to be shaken to provide a consistent drug concentration.

Higher Rates of Persistence and Adherence in Patients with Type 2 Diabetes Initiating Once-Weekly vs Daily Injectable Glucagon-Like Peptide-1 Receptor Agonists in US Clinical Practice (STAY Study).

IntroductionReducing dosing frequency may lower treatment burden and improve persistence and adherence. This retrospective, observational study assessed persistence and adherence in patients with type 2 diabetes (T2D) initiating once-weekly or daily injectable glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in US clinical practice.MethodsThe study used data from adults (≥ 18 years) with T2D who were included in the IBM MarketScan Explorys Claims-EMR Data Set for ≥ 180 days pre-index and ≥ 365 days post-index, were GLP-1 RA and insulin naïve at first claim (index date) for once-weekly or daily injectable GLP-1 RAs (follow-up: index date + 365 days), and were propensity score (PS) matched 1:1 by baseline characteristics. Persistence, defined as the stay time, was assessed using Kaplan–Meier analysis and Cox proportional hazards models. Adherence was defined as a proportion of days covered of 0.8 or greater. To assess whether patients with more advanced disease would benefit from long-acting treatments, patients were matched to the baseline characteristics of basal insulin initiators using inverse probability of treatment weighting (IPTW).ResultsThe PS-matched cohorts (n = 784 each) had similar baseline characteristics. Once-weekly regimens were associated with significantly higher persistence than daily treatments (median stay time: 333 vs 269 days; hazard ratio 0.80 [95% confidence interval 0.71, 0.90]; p < 0.01) and with significantly higher adherence than daily regimens at 6 months and 12 months (p < 0.01 for both). Mean glycated haemoglobin reductions were greater with once-weekly than with daily treatment at 6 months (– 1.1% vs – 0.9%; p < 0.01) and 12 months (– 0.9% vs – 0.7%; p = not significant); adherent patients experienced greater reductions than those with poor adherence. Results were similar in the IPTW-matched analysis.ConclusionIn US clinical practice, once-weekly injectable treatments are associated with better persistence and adherence than daily regimens over 1 year. Once-weekly regimens may also benefit patients with more advanced T2D.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13300-021-01189-6.

Prednisolone Loaded Tamarind Gum Microspheres for Colonic Delivery

The aim of this work was to formulate a novel multiparticulate system having pH sensitive property and specific enzyme biodegradability for colon specific drug delivery of Prednisolone (PD). Natural polysaccharide, Tamarind gum is used for microsphere preparation and Eudratit S- 100 for coating to provide pH controlled drug release. The formulation aims at minimal degradation and optimum delivery of the drug with relatively higher local concentration, which may provide more effective therapy for inflammatory bowel disease including Crohn disease and ulcerative colitis. Tamarind gum microspheres were prepared by emulsion dehydration technique using polymer in ratio of 1:1 to 1: 9. These microspheres were coated with Eudragit S-100 by oil in oil solvent evaporation method using core: coat ration (5:1). Tamarind gum microspheres and Eudragit coated tamarind gum microspheres were evaluated for surface morphology, particle size and size distribution, percentage drug entrapment, surface accumulation studies, in vitro drug release in simulated gastrointestinal fluids. The effect of various formulation variables were studied the prepared microspheres were spherical in shape in the size range of 64 µm to 113 µm, the encapsulation efficiency was in range of 30-72% depending upon the concentration of gum. The drug release was about 14-20% in first four hours of study gradually rises in 5th hour and 85% drug release occurs in 10-12% hr thus showing desirable drug release in the colonic simulated environment. PD tamarind gum microspheres are thought to have the potential to maintain drug concentration within target ranges for a long time, decreasing the side effects caused by concentration fluctuation, ensuring the efficiency of treatment and improving patient compliance by reducing dosing frequency. The animal study done using acetic acid induced colitis model on rats also suggest the anti inflammatory activity of the formulation.

Chitosan nanoparticles facilitate improved intestinal permeation and oral pharmacokinetics of the mast cell stabiliser cromoglycate

Cromoglycate is a mast cell stabiliser typically administered via inhalation or intranasally for the treatment of allergy-based respiratory issues. Oral dosing of cromoglycate remains challenging due to its high solubility but low permeability across epithelial membranes in the gastrointestinal tract: effective formulation strategies are clearly needed. Here, we investigate and preclinically develop chitosan-cromoglycate complexes and associated nano/microparticle formulations with muco-adhesive and permeation enhancing capabilities to overcome the biopharmaceutical challenges for oral dosing.The synthesized complexes were optimized with respect to chitosan grade, particle size, and drug loading and demonstrated up to a 9.3-fold enhancement in permeability across a Caco-2 monolayer for chitosan-cromoglycate particles, compared to the pure drug. This increased intestinal permeability led to improved pharmacokinetic performance of cromoglycate, e.g. up to 1.82-fold increase in relative oral bioavailability when dosed to Sprague-Dawley rats in a fasted state. These findings confirm the potential for chitosan particles to serve as an effective oral delivery vehicle for cromoglycate, with additional formulation optimization presenting the opportunity to reduce dosing frequency for treatment of allergy-based respiratory ailments.

(Rose Bengal)/(Eosin Yellow)-Gold-Polypyrrole Hybrids: A Design for Dual Photo-Active Nano-System with Ultra-High Loading Capacity.

PurposeEnhancement of the photodynamic/photothermal efficiency of two water-soluble dyes, rose bengal (RB) and eosin yellow (EY), via conjugation to a polymeric nano-system gold-polypyrrole nanoparticle (AuPpy NPs).MethodologyA multi-step synthesis method and an in situ one-pot synthesis method were used. Loading percentage, particle size, zeta potential, morphology, UV-Vis-NIR spectrophotometry and in vitro photothermal activity were measured. Then, both hybrid nanocomposites were examined for their cytotoxicity and photocytotoxicity on HepG2 cell line as a model for cancer cells.ResultsDyes loaded in the traditional multi-step method did not exceed 9% w/w, while in the one-pot synthesis method they reached ~67% w/w and ~75% w/w for EY-AuPpy NPs and RB-AuPpy NPs, respectively. UV-Vis-NIR spectrophotometry showed that both nano-systems exhibited intense absorption in the NIR region. The mean size of the nanoparticles was ~31.5 nm (RB-AuPpy NPs) and ~33.6 nm (EY-AuPpy NPs) with zeta potential values of −26.5 mV and −33 mV, respectively. TEM imaging revealed the morphology of both hybrids, showing ultra-nano spherical-shaped gold cores in the case of RB-AuPpy NPs, and different shapes of larger gold cores in the case of EY-AuPpy NPs, both embedded in the polymer film. Conjugation to AuPpy was found to significantly reduce the dark cytotoxicity of both RB and EY, preserving the photocytotoxicity of EY and enhancing the photocytotoxicity of RB.ConclusionGold-polypyrrole nanoparticles represent an effective delivery system to improve the photodynamic and photothermal properties of RB and EY. The in situ one-pot synthesis method provided a means to greatly increase the loading capacity of AuPpy NPs. While both hybrid nanocomposites exhibited greatly diminished dark cytotoxicity, RB-AuPpy NPs showed significantly enhanced photocytotoxicity compared to the free dyes. This pattern enables the safe use of both dyes in high concentrations with sustained action, reducing dose frequency and side effects.

The role of patient preferences in adherence to treatment in chronic disease: a narrative review

Adherence to prescribed medication is important to the management of all diseases, especially those of chronic nature. Drug effectiveness is substantially compromised by therapy nonadherence. We reviewed the available evidences on the impact of patient preferences for therapy on adherence to a prescribed treatment in chronic diseases requiring long-term treatment. A search on PubMed retrieved 699 publications, leading to a selection of 12 publications: 6 on osteoporosis, 2 on moderate-to-severe asthma, 1 on type 1 diabetes, 1 on type 2 diabetes, 1 on kidney transplantation, and 1 on atrial fibrillation. Overall, 8 studies found a positive association between patient preference and adherence to therapy, while the others found no association. In general, overall adherence was considered to be high in the published studies. The reasons for a positive association included reduced dosing frequency, route of administration, lower costs, and favorable safety profile, which is related to the diverse nature of the pathology and its type and duration of treatment. A literature review suggests that achieving good adherence and persistence to therapy requires evaluation of patient preferences. In a period of increasingly limited resources, more effort is warranted to promote better adherence to therapy, especially when patients must self-manage their disease in the long term. Our results further highlight that insufficient attention has been given to the relationship between patient preference and adherence and point out the complex nature of adherence and the need for adequate patient education. More efforts are also needed to better understand the entity of cost savings for payers for specific treatments and the link with patient preference.

Real-World Patient Characteristics, Treatment Patterns and Outcomes for Patients with Atypical Hemolytic Uremic Syndrome Who Have Switched from Eculizumab to Ravulizumab in the USA

IntroductionAtypical hemolytic uremic syndrome (aHUS) is a rare disease that can cause irreversible organ damage or death. Ravulizumab is a long-acting complement C5 inhibitor approved in the USA, Europe, and Japan for the treatment of aHUS. Ravulizumab was engineered from eculizumab to leverage its clinical benefits and safety profile while reducing dosing frequency. This study assessed real-world patient characteristics, treatment patterns, and clinical outcomes for adult and pediatric patients with aHUS in the USA who switched from eculizumab to ravulizumab.MethodsThis retrospective, non-interventional study evaluated the period from January 1, 2012 to March 22, 2021, using US claims data from the Decision Resources Group Real World Data repository. Eligible patients had ≥ 1 medical claim with an aHUS-related International Classification of Diseases 9/10 diagnosis code and ≥ 1 medical or pharmacy claim for treatment with eculizumab or ravulizumab. Patients with evidence of paroxysmal nocturnal hemoglobinuria, myasthenia gravis, neuromyelitis optical spectrum disorder or Shiga toxin Escherichia coli-related hemolytic uremic syndrome in the 3 months prior to their first aHUS-related treatment were excluded. A patient was classified as ‘switched’ if they had ≥ 1 claim for eculizumab followed by an initial claim for ravulizumab from 14 to 30 days after the last eculizumab claim. Patients were required to have ≥ 3 months of continuous enrollment in the database prior to their first ravulizumab claim. Ravulizumab treatment was considered to be continuous if all treatment intervals were ≤ 63 days.Data extracted included: demographics and clinical characteristics at the time of switching to ravulizumab; treatment patterns (including service setting, treatment history before switching to ravulizumab, and subsequent adherence); and clinical outcomes (dialysis, plasma exchange [PE], kidney transplant, and utilization of other end-stage renal disease [ESRD] services) in the 6 months before and after switching to ravulizumab. Data were summarized using descriptive statistics.ResultsOverall, 2101 patients had ≥ 1 eculizumab or ravulizumab claim and an aHUS-related diagnosis. Of these patients, 227 had claims for both eculizumab and ravulizumab with ≥ 3 months of continuous enrollment data before the first ravulizumab claim. The median (lower quartile, upper quartile) treatment interval between the last eculizumab claim and the first ravulizumab claim was 15 (14, 41) days.In total, 131 patients met the ‘switched’ criteria. Table 1 presents patient characteristics at the time of switching from eculizumab to ravulizumab. Outpatient facilities were the most common places of service for initiation of switch to ravulizumab (n = 41/89 patients [46%]); private practice facilities were the most common sites for administration of ravulizumab maintenance treatment (n = 84/213 claims [39%]).Prior to switching to ravulizumab, the median (lower quartile, upper quartile) duration between the first and last eculizumab claim was 788 (252, 1719) days. Among the 95 patients with ≥ 6 months of continuous enrollment after switching to ravulizumab, 73 (77%) patients were treated with ravulizumab continuously for ≥ 6 months. Selected clinical outcomes in the 6 months before and after switching to ravulizumab treatment are presented in Table 2. Although no inferential statistical comparisons were made, data show that fewer switched patients underwent dialysis or utilized other ESRD services in the 6-month post-switch period (with no recorded cases of PE or kidney transplant) compared with the 6-month pre-switch period.Discussion and conclusionsThis study provides real-world data on clinical characteristics and treatment patterns for patients with aHUS who have switched from eculizumab to ravulizumab. The majority of patients switching to ravulizumab were treated continuously for ≥ 6 months according to the treatment schedule in the prescribing information. Ongoing analyses with longer follow-up time will provide inferential assessment of the clinical and economic impacts of switching to ravulizumab. [Display omitted] DisclosuresWang: Alexion: Current Employment; AstraZeneca: Current Employment. Al-Dakkak: Alexion: Current Employment; AstraZeneca: Current Employment. Garlo: Alexion: Current Employment; AstraZeneca: Current Employment. Ong: Alexion: Current Employment; AstraZeneca: Current Employment. Tomazos: Alexion, AstraZeneca Rare Disease: Current Employment. Mahajerin: Alexion: Consultancy; AstraZeneca: Current Employment.