Evaluation of Loco-Regional Skin Toxicity Induced by an In Situ Forming Depot after a Single Subcutaneous Injection at Different Volumes and Flow Rates in Göttingen Minipigs

The present study aims to investigate the loco-regional tolerability and injection parameters (i.e., flow rate and administration volume) of an in situ forming depot (ISFD) in Göttingen minipigs, to secure both the therapeutic procedure and compliance in chronic medical prescriptions. The ISFD BEPO® technology (MedinCell S.A.) is investigated over 10 days, after a single subcutaneous injection of test item based on a DMSO solution of diblock and triblock polyethylene glycol-polylactic acid copolymers. Injection sites are systematically observed for macroscopic loco-regional skin reactions as well as ultrasound scanning, enabling longitudinal in vivo imaging of the depot. Observations are complemented by histopathological examinations at 72 h and 240 h post-injection. Overall, no treatment-emergent adverse effects are macroscopically or microscopically observed at the subcutaneous injection sites, for the tested injection flow rates of 1 and 8 mL/min and volumes of 0.2 and 1 mL. The histopathology examination confirms an expected foreign body reaction, with an intensity depending on the injected volume. The depot morphology is similar irrespective of the administration flow rates. These results indicate that the ISFD BEPO® technology can be considered safe when administered subcutaneously in Göttingen minipigs, a human-relevant animal model for subcutaneous administrations, in the tested ranges.

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Development of In Situ Self-Assembly Nanoparticles to Encapsulate Lopinavir and Ritonavir for Long-Acting Subcutaneous Injection

Pharmaceutics ◽

10.3390/pharmaceutics13060904 ◽

2021 ◽

Vol 13 (6) ◽

pp. 904

Author(s):

Irin Tanaudommongkon ◽

Asama Tanaudommongkon ◽

Xiaowei Dong

Keyword(s):

Sustained Release ◽

Trough Concentration ◽

Self Assembly ◽

Subcutaneous Injection ◽

Drug Loading ◽

Entrapment Efficiency ◽

Long Acting

Most antiretroviral medications for human immunodeficiency virus treatment and prevention require high levels of patient adherence, such that medications need to be administered daily without missing doses. Here, a long-acting subcutaneous injection of lopinavir (LPV) in combination with ritonavir (RTV) using in situ self-assembly nanoparticles (ISNPs) was developed to potentially overcome adherence barriers. The ISNP approach can improve the pharmacokinetic profiles of the drugs. The ISNPs were characterized in terms of particle size, drug entrapment efficiency, drug loading, in vitro release study, and in vivo pharmacokinetic study. LPV/RTV ISNPs were 167.8 nm in size, with a polydispersity index of less than 0.35. The entrapment efficiency was over 98% for both LPV and RTV, with drug loadings of 25% LPV and 6.3% RTV. A slow release rate of LPV was observed at about 20% on day 5, followed by a sustained release beyond 14 days. RTV released faster than LPV in the first 5 days and slower than LPV thereafter. LPV trough concentration remained above 160 ng/mL and RTV trough concentration was above 50 ng/mL after 6 days with one subcutaneous injection. Overall, the ISNP-based LPV/RTV injection showed sustained release profiles in both in vitro and in vivo studies.

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The osteogenic differentiation of rat muscle-derived stem cells in vivo within in situ-forming chitosan scaffolds

Biomaterials ◽

10.1016/j.biomaterials.2008.08.005 ◽

2008 ◽

Vol 29 (33) ◽

pp. 4420-4428 ◽

Cited By ~ 51

Author(s):

Kyung Sook Kim ◽

Jung Hwa Lee ◽

Hyun Hee Ahn ◽

Ju Young Lee ◽

Gilson Khang ◽

...

Keyword(s):

Stem Cells ◽

Osteogenic Differentiation ◽

Rat Muscle ◽

In Situ Forming ◽

Chitosan Scaffolds

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In situ forming chitosan hydrogels: Preliminary evaluation of the in vivo inflammatory response

Materials Science and Engineering C ◽

10.1016/j.msec.2017.02.050 ◽

2017 ◽

Vol 75 ◽

pp. 279-285 ◽

Cited By ~ 9

Author(s):

Maria José Moura ◽

João Brochado ◽

Maria Helena Gil ◽

Maria Margarida Figueiredo

Keyword(s):

Inflammatory Response ◽

Preliminary Evaluation ◽

In Situ Forming ◽

Chitosan Hydrogels

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In Vitro and In Vivo Drug Release from a Novel In Situ Forming Drug Delivery System

Pharmaceutical Research ◽

10.1007/s11095-007-9478-y ◽

2007 ◽

Vol 25 (6) ◽

pp. 1347-1354 ◽

Cited By ~ 38

Author(s):

Heiko Kranz ◽

Erol Yilmaz ◽

Gayle A. Brazeau ◽

Roland Bodmeier

Keyword(s):

Drug Delivery ◽

Drug Release ◽

Drug Delivery System ◽

Delivery System ◽

In Situ Forming

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Curcumin-incorporated crosslinked sodium alginate-g-poly (N-isopropyl acrylamide) thermo-responsive hydrogel as an in-situ forming injectable dressing for wound healing: in vitro characterization and in vivo evaluation

Carbohydrate Polymers ◽

10.1016/j.carbpol.2021.118434 ◽

2021 ◽

pp. 118434

Author(s):

Mohammad Zakerikhoob ◽

Sahar Abbasi ◽

Gholamhossein Yousefi ◽

Maral Mokhtari ◽

Mohammad Sadegh Noorbakhsh

Keyword(s):

Wound Healing ◽

Sodium Alginate ◽

In Vivo Evaluation ◽

In Situ Forming ◽

In Vitro Characterization ◽

Isopropyl Acrylamide

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In-vitro, ex-vivo, and in-vivo release evaluation of in situ forming buprenorphine implants using mixture of PLGA copolymers and additives

International Journal of Polymeric Materials ◽

10.1080/00914037.2018.1525541 ◽

2018 ◽

Vol 68 (16) ◽

pp. 965-977 ◽

Cited By ~ 1

Author(s):

Hossein Kamali ◽

Elham Khodaverdi ◽

Farzin Hadizadeh ◽

Seyed Ahmad Mohajeri ◽

Younes Kamali ◽

...

Keyword(s):

Ex Vivo ◽

In Situ Forming ◽

In Vivo Release

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One-week in vivo sustained release of a peptide formulated into in situ forming implants

International Journal of Pharmaceutics ◽

10.1016/j.ijpharm.2017.02.046 ◽

2017 ◽

Vol 521 (1-2) ◽

pp. 357-360 ◽

Cited By ~ 6

Author(s):

Marianne Parent ◽

Igor Clarot ◽

Sébastien Gibot ◽

Marc Derive ◽

Philippe Maincent ◽

...

Keyword(s):

Sustained Release ◽

In Situ Forming ◽

In Situ Forming Implants

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Sucrose Acetate Isobutyrate as an In situ Forming Implant for Sustained Release of Local Anesthetics

Current Drug Delivery ◽

10.2174/1567201816666181119112952 ◽

2019 ◽

Vol 16 (4) ◽

pp. 331-340

Author(s):

Hanmei Li ◽

Yuling Xu ◽

Yuna Tong ◽

Yin Dan ◽

Tingting Zhou ◽

...

Keyword(s):

Drug Delivery ◽

Sustained Release ◽

Local Anesthetics ◽

Subcutaneous Injection ◽

In Vitro Release ◽

Pharmacokinetic Analysis ◽

Burst Release

Objective: In this study, an injectable Sucrose Acetate Isobutyrate (SAIB) drug delivery system (SADS) was designed and fabricated for the sustained release of Ropivacaine (RP) to prolong the duration of local anesthesia. Methods: By mixing SAIB, RP, and N-methyl-2-pyrrolidone, the SADS was prepared in a sol state with low viscosity before injection. After subcutaneous injection, the pre-gel solution underwent gelation in situ to form a drug-released depot. Result: The in vitro release profiles and in vivo pharmacokinetic analysis indicated that RP-SADS had suitable controlled release properties. Particularly, the RP-SADS significantly reduced the initial burst release after subcutaneous injection in rats. Conclusion: In a pharmacodynamic analysis of rats, the duration of nerve blockade was prolonged by over 3-fold for the RP-SADS formulation compared to RP solution. Additionally, RP-SADS showed good biocompatibility in vitro and in vivo. Thus, the SADS-based depot technology is a safe drug delivery strategy for the sustained release of local anesthetics with long-term analgesia effects.

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