scholarly journals Subcutaneous Injection Performance in Yucatan Miniature Pigs with and without Human Hyaluronidase and Auto-injector Tolerability in Humans

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Galen H. Shi ◽  
Robert J. Connor ◽  
David S. Collins ◽  
David W. Kang
Keyword(s):  
Injection Site ◽  
Subcutaneous Injection ◽  
Therapeutic Agents ◽  
Injection Time ◽  
Miniature Pigs ◽  
Recombinant Human Hyaluronidase ◽  
Auto Injector ◽  
Over Time

AbstractRecombinant human hyaluronidase PH20 (rHuPH20) facilitates subcutaneous (SC) delivery of co-administered therapeutic agents by locally and transiently degrading hyaluronan in the SC space, and can be administered with therapeutics using a variety of devices. Two SC delivery studies were carried out to assess auto-injector (AI) performance, each in 18 Yucatan miniature pigs. Abdominal injections were administered using three auto-injectors of 1 mL (AI1) and 2 mL (AI2 and sAI2) with different injection speeds and depths (5.5–7.5 mm) and two pre-filled syringe (PFS) devices of 1 and 2 mL. The injection included a placebo buffer with and without rHuPH20 to evaluate the effect of rHuPH20 on SC injection performance. The feasibility of using similar devices to deliver a placebo buffer in humans was investigated. rHuPH20 was not studied in humans. In miniature pigs, postinjection swelling was evident for most PFS/AI injections, particularly 2 mL. Swelling heights and back leakage were typically lower with rHuPH20 co-administration versus placebo for most device configurations (1 or 2 mL PFS or AI). Auto-injections with versus without rHuPH20 also resulted in reduced swelling firmness and faster swelling resolution over time. Slow injections with rHuPH20 had shorter and more consistent injection time versus placebo. In humans, minimal injection site swelling and negligible back leakage were observed for 2-mL injections of placebo, while more erythema was observed in humans versus miniature pigs. Even at high delivery rates with PFS or AI, the addition of rHuPH20 resulted in improved SC injection performance versus placebo in miniature pigs.

scholarly journals Injectable Thermosensitive Formulation Based on Polyurethane Hydrogel/Mesoporous Glasses for Sustained Co-Delivery of Functional Ions and Drugs

Pharmaceutics ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 501 ◽  
Author(s):  
Monica Boffito ◽  
Carlotta Pontremoli ◽  
Sonia Fiorilli ◽  
Rossella Laurano ◽  
Gianluca Ciardelli ◽  
...  
Keyword(s):  
Therapeutic Agents ◽  
Chemical Degradation ◽  
Burst Release ◽  
Injectable Hydrogels ◽  
Micro Particles ◽  
Custom Made ◽  
Thermosensitive Hydrogels ◽  
Polyurethane Hydrogel ◽  
Over Time ◽  
Incipient Wetness Method

Mini-invasively injectable hydrogels are widely attracting interest as smart tools for the co-delivery of therapeutic agents targeting different aspects of tissue/organ healing (e.g., neo-angiogenesis, inflammation). In this work, copper-substituted bioactive mesoporous glasses (Cu-MBGs) were prepared as nano- and micro-particles and successfully loaded with ibuprofen through an incipient wetness method (loaded ibuprofen approx. 10% w/w). Injectable hybrid formulations were then developed by dispersing ibuprofen-loaded Cu-MBGs within thermosensitive hydrogels based on a custom-made amphiphilic polyurethane. This procedure showed almost no effects on the gelation potential (gelation at 37 °C within 3–5 min). Cu2+ and ibuprofen were co-released over time in a sustained manner with a significantly lower burst release compared to MBG particles alone (burst release reduction approx. 85% and 65% for ibuprofen and Cu2+, respectively). Additionally, released Cu2+ species triggered polyurethane chemical degradation, thus enabling a possible tuning of gel residence time at the pathological site. The overall results suggest that hybrid injectable thermosensitive gels could be successfully designed for the simultaneous localized co-delivery of multiple therapeutics.

scholarly journals P620 Maintenance of clinical remission with SB5 biosimilar after switch from adalimumab originator: Real-life experience of a tertiary referral centre

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S515-S515 ◽  
Author(s):  
G Dragoni ◽  
A Pieraccini ◽  
S Bagnoli ◽  
S Caini ◽  
G Macrì ◽  
...  
Keyword(s):  
Injection Site ◽  
Clinical Remission ◽  
Life Experience ◽  
Cox Regression ◽  
Injection Site Reaction ◽  
Real Life ◽  
Site Reaction ◽  
Tertiary Referral Centre ◽  
Historical Cohort ◽  
Over Time

Abstract Background Adalimumab (ADM) biosimilars have been demonstrated as safe and effective as the ‘originator’ in trials for other autoimmune disorders, but real-life evidence in inflammatory bowel diseases (IBD) is lacking. The aim of the study was to demonstrate maintenance of clinical remission (CR) after switch from ADM ‘originator’ to biosimilar SB5. Methods Data were retrospectively collected from November 2018 to September 2019. All IBD patients in CR after at least 6 months of ‘originator’ and switched to SB5 were included. The primary outcomes were maintenance of CR at 6 months after switch (defined as Partial Mayo Score 0–1 for ulcerative colitis and Harvey–Bradshaw Index ≤4 for Crohn’s disease) and overall comparable safety. A historical cohort of patients treated only with the ‘originator’ was included for comparison, using a Cox regression model with a time-varying covariate. Results In total, 96 patients were included. Baseline characteristics of the cohort are reported in Table 1. Maintenance of CR after 6 months of switch was reported in 89/96 (92.7%) patients. Levels of C-reactive protein (CRP) significantly increased over time from baseline to 6 months (from 2.67 ± 2.61 to 4.98 ± 5.81 mg/dl, p = 0.03), but no difference between the two time points was found when considering a relevant flare only for CRP above the lab cut-off (5 mg/dl). A comparison of CR persistence over time between ‘originator’ cohort and SB5 ‘switching’ cohort did not show any statistical difference (Hazard Ratio 1.07, 95% CI 0.57 – 2.01). With regard to adverse events, SB5 showed an overall safety profile, with only 2/96 (2.1%) patients interrupting the treatment due to anti-TNF-induced psoriasis. In 42/96 (43.8%) of patients, at least one injection site reaction was reported; only in one case a re-switch to ‘originator’ was needed for local intolerance. Conclusion SB5 is safe and effective in maintaining CR after switching from the ‘originator’. Injection site reaction is a frequent but usually manageable side effect. Larger multi-centre cohort and endoscopic assessment are needed to confirm the initial findings.

scholarly journals Functional intersection of the kallikrein-related peptidases (KLKs) and thrombostasis axis

2010 ◽  
Vol 391 (4) ◽  
Author(s):  
Michael Blaber ◽  
Hyesook Yoon ◽  
Maria A. Juliano ◽  
Isobel A. Scarisbrick ◽  
Sachiko I. Blaber
Keyword(s):  
Initial Conditions ◽  
Tissue Injury ◽  
Large Body ◽  
Therapeutic Agents ◽  
Specific Interactions ◽  
Complete Understanding ◽  
Functional Interaction ◽  
Regulatory Interactions ◽  
Normal Health ◽  
Over Time

Abstract A large body of emerging evidence indicates a functional interaction between the kallikrein-related peptidases (KLKs) and proteases of the thrombostasis axis. These interactions appear relevant for both normal health as well as pathologies associated with inflammation, tissue injury, and remodeling. Regulatory interactions between the KLKs and thrombostasis proteases could impact several serious human diseases, including neurodegeneration and cancer. The emerging network of specific interactions between these two protease families appears to be complex, and much work remains to elucidate it. Complete understanding how this functional network resolves over time, given specific initial conditions, and how it might be controllably manipulated, will probably contribute to the emergence of novel diagnostics and therapeutic agents for major diseases.

scholarly journals Synthesis of the Nakanishi Ring-Locked Retinoid

2011 ◽  
Vol 2011 ◽  
pp. 1-8
Author(s):  
Jamie B. Côté ◽  
Tan D. Quach ◽  
Andrey P. Demenev ◽  
David S. Garvey ◽  
Judd M. Berman
Keyword(s):  
Therapeutic Agents ◽  
Proof Of Concept ◽  
Synthetic Route ◽  
Biological Tool ◽  
Purification Protocol ◽  
Over Time

An optimized synthetic route to prepare ring-locked retinoid 1a has been developed. We fully describe a purification protocol that provides isomerically pure 1a in support of on-going proof of concept studies for the development of therapeutic agents to treat human ADRP. Additionally, we have found that isomerically pure 1a can be stored in amber vials under argon at −20°C for use over time (up to six months) without degradation. Thus, enabling 1a to be an accessible and valuable biological tool.

scholarly journals Predictors of Subcutaneous Injection Site Reactions to Sustained-Release Buprenorphine in Rhesus Macaques (Macaca mulatta)

2021 ◽  
Author(s):  
Andrew J Haertel ◽  
Matthew A Schultz ◽  
Lois M Colgin ◽  
Amanda L Johnson
Keyword(s):  
Sustained Release ◽  
Injection Site ◽  
Macaca Mulatta ◽  
Subcutaneous Injection ◽  
Rhesus Macaques ◽  
Single Case ◽  
Subcutaneous Tissue ◽  
Injection Site Reaction ◽  
Reaction Rates ◽  
Injection Site Reactions

Subcutaneous injection site reactions to sustained-release buprenorphine hydrochloride (Buprenorphine SR) in macaqueshave been reported in only a single case report. In the current study, we evaluated the incidence rate and predictors ofbuprenorphine SR reactions in the subcutaneous tissue of rhesus macaques (Macaca mulatta) based on retrospective reviewof macaque buprenorphine SR injection records. Potentially predictive variables were identified with logistic regressionmodeling and were evaluated using model selection based on Akaike information criterion. Record review revealed subcutaneoustissue reactions occurred in 52 (3%) of 1559 injections and were noted between 4 and 311 d after injection. Modelselection showed that body weight and MHC allele Mamu-B*29 were the best predictors of subcutaneous reactions. Basedon these results, we recommend consideration of potential risk factors prior to the administration of buprenorphine SR toa rhesus macaque. In addition, the authors advise that using the highest concentration of buprenorphine SR available mayreduce injection site reaction rates due to the injection of less copolymer.

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