Comparative route of administration studies using therapeutic siRNAs show widespread gene modulation in Dorset sheep

Lipids are used as vehicles for the preparation of various formulations prescribed for administrations, including emulsions, ointments, suspension, tablets, and suppositories. The first parental nano-emulsion was discovered from the 1950s when it was added to the intravenous administration of lipid and lipid-soluble substances. Lipid-based drug delivery systems are important nowadays. Solid nanoparticles (SLN) and Nanostructured lipid carriers (NLC) are very proficient due to the ease of production process, scale-up capability, bio-compatibility, the biodegradability of formulation components and other specific features of the proposed route. The administration or nature of the materials must be loaded into these delivery systems. The main objectives of this review are to discuss an overview of second-generation nanoparticles, their limitations, structures, and route of administration, with emphasis on the effectiveness of such formulations. NLC is the second generation of lipid nanoparticles having a structure like nanoemulsion. The first generation of nanoparticles was SLN. The difference between both of them is at its core. Both of them are a colloidal carrier in submicron size in the range of 40-1000 nm. NLC is the most promising novel drug delivery system over the SLN due to solving the problem of drug loading and drug crystallinity. Solid and liquid lipids combination in NLC formation, improve its quality as compare to SLN. NLC has three types of structures: random, amorphous, and multiple. The random structure containing solid-liquid lipids and consisting crystal and the liquid lipid irregular in shape; thereby enhance the ability of the lipid layer to pass through the membrane. The second is the amorphous structure. It is less crystalline in nature and can prevent the leakage of the loaded drug. The third type is multiple structures, which have higher liquid lipid concentrations than other types. The excipients used to form the NLC are bio-compatible, biodegradable and non-irritating, most of which can be detected using GRAS. NLC is a promising delivery system to deliver the drug through pulmonary, ocular, CNS, and oral route of administration. Various methods of preparation and composition of NLC influence its stability Parameters. In recent years at the educational level, the potential of NLC as a delivery mechanism targeting various organs has been investigated in detail.

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POS1234 IMPACT OF THE CHANGE IN ADMINISTRATION ROUTE OF TOCILIZUMAB AND ABATACEPT, DUE TO THE COVID-19 LOCKDOWN ON DISEASE ACTIVITY IN PATIENTS WITH RHEUMATOID ARTHRITIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.3126 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 900.1-900

Author(s):

L. Diebold ◽

T. Wirth ◽

V. Pradel ◽

N. Balandraud ◽

E. Fockens ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Physical Activity ◽

Disease Activity ◽

Univariate Analysis ◽

Route Of Administration ◽

Anxiety And Depression ◽

Administration Route ◽

Factors Associated ◽

The Impact

Background:Among therapeutics used to treat rheumatoid arthritis (RA), Tocilizumab (TCZ) and Abatacept (ABA) are both biologic agents that can be delivered subcutaneously (SC) or intravenously (IV). During the first COVID-19 lockdown in France, all patients treated with IV TCZ or IV ABA were offered the option to switch to SC administration.Objectives:The primary aim was to assess the impact of changing the route of administration on the disease activity. The second aim was to assess whether the return to IV route at the patient’s request was associated with disease activity variation, flares, anxiety, depression and low physical activity during the lockdown.Methods:We conducted a prospective monocentric observational study. Eligibility criteria: Adult ≥ 18 years old, RA treated with IV TCZ or IV ABA with a stable dose ≥3 months, change in administration route (from IV to SC) between March 16, 2020, and April 17, 2020. The following data were collected at baseline and 6 months later (M6): demographics, RA characteristics, treatment, history of previous SC treatment, disease activity (DAS28), self-administered questionnaires on flares, RA life repercussions, physical activity, anxiety and depression (FLARE, RAID, Ricci &Gagnon, HAD).The primary outcome was the proportion of patients with a DAS28 variation>1.2 at M6. Analyses: Chi2-test for quantitative variables and Mann-Whitney test for qualitative variables. Factors associated with return to IV route identification was performed with univariate and multivariate analysis.Results:Among the 84 patients who were offered to switch their treatment route of administration, 13 refused to change their treatment. Among the 71 who switched (48 TCZ, 23 ABA), 58 had a M6 follow-up visit (13 lost of follow-up) and DAS28 was available for 49 patients at M6. Main baseline characteristics: female 81%, mean age 62.7, mean disease duration: 16.0, ACPA positive: 72.4%, mean DAS28: 2.01, previously treated with SC TCZ or ABA: 17%.At M6, the mean DAS28 variation was 0.18 ± 0.15. Ten (12.2%) patients had a DAS28 worsening>1.2 (ABA: 5/17 [29.4%] and TCZ: 5/32 [15.6%], p= 0.152) and 19 patients (32.8%) had a DAS28 worsening>0.6 (ABA: 11/17 [64.7%] and TCZ: 8/32 [25.0%], p= 0.007).At M6, 41 patients (77.4%) were back to IV route (26 TCZ, 15 ABA) at their request. The proportion of patients with a DAS28 worsening>1.2 and>0.6 in the groups return to IV versus SC maintenance were 22.5%, 42.5% versus 11.1% and 22.2% (p=0.4), respectively. The univariate analysis identified the following factors associated with the return to IV route: HAD depression score (12 vs 41, p=0.009), HAS anxiety score (12 vs 41, p=0.047) and corticosteroid use (70% vs 100%, p=0.021), in the SC maintenance vs return to IV, respectively.Conclusion:The change of administration route of TCZ and ABA during the first COVID-19 lockdown was infrequently associated with a worsening of RA disease. However, the great majority of the patients (77.4%) request to return to IV route, even without disease activity worsening. This nocebo effect was associated with higher anxiety and depression scores.Disclosure of Interests:None declared

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Optimization of dose and route of administration of the P‐glycoprotein inhibitor, valspodar (PSC‐833) and the P‐glycoprotein and breast cancer resistance protein dual‐inhibitor, elacridar (GF120918) as dual infusion in rats

Pharmacology Research & Perspectives ◽

10.1002/prp2.740 ◽

2021 ◽

Vol 9 (2) ◽

Author(s):

Christopher Rowbottom ◽

Alicia Pietrasiewics ◽

Taras Tuczewycz ◽

Richard Grater ◽

Daniel Qiu ◽

...

Keyword(s):

Breast Cancer ◽

Breast Cancer Resistance Protein ◽

Route Of Administration ◽

Cancer Resistance ◽

Dual Inhibitor ◽

Psc 833 ◽

P Glycoprotein ◽

Resistance Protein

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1356. Ribavirin Use in Hospitalized Children

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1538 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S689-S690

Author(s):

William R Otto ◽

Giyoung Lee ◽

Cary Thurm ◽

Jeffrey Gerber ◽

Adam Hersh

Keyword(s):

Diagnosis Related Groups ◽

Pediatric Population ◽

Health Information System ◽

International Classification Of Diseases ◽

Route Of Administration ◽

Administrative Database ◽

Hospitalized Children ◽

Syncytial Virus ◽

Tract Infections ◽

Over Time

Abstract Background Respiratory syncytial virus (RSV) infection is a significant cause of morbidity and mortality in immunocompromised children. Aerosolized ribavirin is approved for treatment of RSV lower respiratory tract infections. However, due to high cost, challenges to administration and uncertainty about benefit, use is limited. Recent studies in adult patients have reported similar outcomes between patients treated with aerosolized and oral ribavirin. We sought to characterize trends in use of ribavirin for hospitalized children. Methods We used the Pediatric Health Information System (PHIS), an administrative database which contains resource utilization data from 52 children’s hospitals, to perform a retrospective analysis of children hospitalized between January 1, 2010 through December 31, 2019 who were billed for ribavirin treatment. Data related to ribavirin use (number of courses, route of administration) and clinical characteristics were abstracted. International Classification of Diseases, 9th Revision (ICD-9) or 10th Revision (ICD-10) codes and All Patients Refined Diagnosis Related Groups (APR DRG) classifications were used to define underlying clinical conditions and illness severity. Summary statistics were used to describe patient characteristics and the use of ribavirin. Results Thirty-eight hospitals reported ribavirin use; 1 hospital was excluded due to inaccuracies in charge coding. We identified 837 children who received 937 courses of ribavirin (Table 1). The overall frequency of ribavirin use was unchanged over the study period, and the number of ribavirin treatment courses per hospital ranged from 1 to 228 (Figure 1). The most frequent routes of administration were inhalation (603/937, 64%) and oral (322/937, 34%). There was a decrease in the use of aerosolized ribavirin over time, with a corresponding increase in the use of oral ribavirin (Figure 2). Table 1: Patient demographics (N=837) Figure 1: Total ribavirin treatment courses over the study period (a) by year and (b) by treating hospital Figure 2: (a) Route of administration (inhalation versus oral), by year during the study period and (b) use of oral ribavirin over time during the study period Conclusion Although overall prescribing rates of ribavirin in hospitalized children have remained stable, use varies widely across centers and the proportion of oral ribavirin use has increased over time. Comparative effectiveness studies are needed in the pediatric population to evaluate outcomes of children treated with aerosolized vs. oral ribavirin. Disclosures All Authors: No reported disclosures

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Anticoagulation Treatment in Cancer-Associated Venous Thromboembolism: Assessment of Patient Preferences Using a Discrete Choice Experiment (COSIMO Study)

Thrombosis and Haemostasis ◽

10.1055/s-0040-1714739 ◽

2020 ◽

Author(s):

Nils Picker ◽

Agnes Y. Lee ◽

Alexander T. Cohen ◽

Anthony Maraveyas ◽

Jan Beyer-Westendorf ◽

...

Keyword(s):

Venous Thromboembolism ◽

Oral Administration ◽

Discrete Choice Experiment ◽

Discrete Choice ◽

Patient Preferences ◽

Choice Experiment ◽

Oral Anticoagulants ◽

Daily Intake ◽

Anticoagulation Therapy ◽

Route Of Administration

Abstract Introduction Clinical guidelines recommend anticoagulation therapy for the treatment of cancer-associated venous thromboembolism (VTE), but little is known about preferences. Therefore, the objective of this discrete choice experiment (DCE) was to elucidate patient preferences regarding anticoagulation convenience attributes. Methods Adult patients with cancer-associated VTE who switched to direct oral anticoagulants were included in a single-arm study (COSIMO). Patients were asked to decide between hypothetical treatment options based on a combination of the following attributes: route of administration (injection/tablet), frequency of intake (once/twice daily), need for regular controls of the international normalized ratio (INR) at least every 3 to 4 weeks (yes/no), interactions with food/alcohol (yes/no), and distance to treating physician (1 vs. 20 km) as an additional neutral attribute. DCE data were collected by structured telephone interviews and analyzed based on a conditional logit regression. Results Overall, 163 patients (mean age 63.7 years, 49.1% female) were included. They strongly preferred oral administration compared with self-injections (importance of this attribute for overall treatment decisions: 73.8%), and a treatment without dietary restrictions (11.8%). Even if these attributes were less important (7.2% and 6.5%, respectively), patients indicated a preference for a shorter distance to the treating physician and once-daily dosing compared with twice-daily intake. “Need for regular controls of INR at least every 3 to 4 weeks” showed no significant impact on the treatment decision (0.7%). Conclusion This study showed that treatment-related decision making in cancer-associated VTE, assuming comparable effectiveness and safety of anticoagulant treatments, is predominantly driven by “route of administration,” with patients strongly preferring oral administration.

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