Effect of implant formation on drug release kinetics of in situ forming implants

Suh, Min Sung; Kastellorizios, Michail; Tipnis, Namita; Zou, Yuan; Wang, Yan; Choi, Stephanie; Burgess, Diane J.

doi:10.1016/j.ijpharm.2020.120105

Cited by 30 publications

(8 citation statements)

References 30 publications

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“…Rapid gelation is important for in situ formation of drug delivery depots to reduce the diffusion of drug(s) from the depot and potential burst release. Quick gelation after injectable administration is also important for our system in order to reduce the availability of the peptoid-peptide ester linkage with the drug to water within the subcutaneous space, providing a diffusion barrier to rapid drug cleavage by hydrolysis . There are several ways in which time for gelation can be defined: a) the time at which the storage modulus ( G ′) and loss modulus ( G ″) cross indicating greater solid-like behavior; b) the time point at which G ′ is greater by 1 order of magnitude than G ″; and c) the time at which G ′ and G ″ begin to stabilize/plateau.…”

Section: Results and Discussionsupporting

confidence: 70%

In Situ Forming, Enzyme-Responsive Peptoid-Peptide Hydrogels: An Advanced Long-Acting Injectable Drug Delivery System

Coulter,

Pentlavalli,

et al. 2024

J. Am. Chem. Soc.

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Long-acting drug delivery systems are promising platforms to improve patient adherence to medication by delivering drugs over sustained periods and removing the need for patients to comply with oral regimens. This research paper provides a proofof-concept for the development of a new optimized in situ forming injectable depot based on a tetrabenzylamine-tetraglycine-D-lysine-O-phospho-D-tyrosine peptoid-D-peptide formulation ((NPhe) 4 GGGGk(AZT)y(p)-OH). The chemical versatility of the peptoid-peptide motif allows low-molecular-weight drugs to be precisely and covalently conjugated. After subcutaneous injection, a hydrogel depot forms from the solubilized peptoid-peptide-drug formulation in response to phosphatase enzymes present within the skin space. This system is able to deliver clinically relevant concentrations of a model drug, the antiretroviral zidovudine (AZT), for 35 days in Sprague−Dawley rats. Oscillatory rheology demonstrated that hydrogel formation began within ∼30 s, an important characteristic of in situ systems for reducing initial drug bursts. Gel formation continued for up to ∼90 min. Small-angle neutron scattering data reveal narrow-radius fibers (∼0.78−1.8 nm) that closely fit formation via a flexible cylinder elliptical model. The inclusion of non-native peptoid monomers and D-variant amino acids confers protease resistance, enabling enhanced biostability to be demonstrated in vitro. Drug release proceeds via hydrolysis of an ester linkage under physiological conditions, releasing the drug in an unmodified form and further reducing the initial drug burst. Subcutaneous administration of (NPhe) 4 GGGGk(AZT)y(p)-OH to Sprague−Dawley rats resulted in zidovudine blood plasma concentrations within the 90% maximal inhibitory concentration (IC 90 ) range (30−130 ng mL −1 ) for 35 days.

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Section: Results and Discussionsupporting

confidence: 70%

In Situ Forming, Enzyme-Responsive Peptoid-Peptide Hydrogels: An Advanced Long-Acting Injectable Drug Delivery System

Coulter,

Pentlavalli,

et al. 2024

J. Am. Chem. Soc.

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show abstract

“…Ideally, injections should be made directly into the matrix, as this to a larger extent mimics the in vivo conditions. However, defining the geometry of in situ forming injectables in in vitro release studies is currently a hot topic [ 39 , 40 , 41 ], as it may be advantageous for certain formulation types and for reducing between-experiment variability. To study the impact of the geometrical shape of formulations on the diffusion patterns and the rate of cAMP release, experiments were conducted with different cavity geometries (described in Section 3.2 ).…”

Section: Resultsmentioning

confidence: 99%

Methodological Considerations in Development of UV Imaging for Characterization of Intra-Tumoral Injectables Using cAMP as a Model Substance

Bock

Boetker

Larsen

et al. 2022

IJMS

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A UV imaging release-testing setup comprising an agarose gel as a model for tumorous tissue was developed. The setup was optimized with respect to agarose concentration (0.5% (w/v)), injection procedure, and temperature control. A repeatable injection protocol was established allowing injection into cavities with well-defined geometries. The effective resolution of the SDi2 UV imaging system is 30–80 µm. The linear range of the imaging system is less than that of typical spectrophotometers. Consequently, non-linear cAMP calibration curves were applied for quantification at 280 nm. The degree of deviation from Beer’s law was affected by the background absorbance of the gel matrix. MATLAB scripts provided hitherto missing flexibility with respect to definition and utilization of quantification zones, contour lines facilitating visualization, and automated, continuous data analysis. Various release patterns were observed for an aqueous solution and in situ forming Pluronic F127 hydrogel and PLGA implants containing cAMP as a model for STING ligands. The UV imaging and MATLAB data analysis setup constituted a significant technical development in terms of visualizing behavior for injectable formulations intended for intra-tumoral delivery, and, thereby, a step toward establishment of a bio-predictive in vitro release-testing method.

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“…The section of the loading platform of in situ implants is important for bone repair. [51,52] In this section, we will summarize different platforms over the past decades used in bone regeneration.…”

Section: Loading Platforms For Bone Regenerationmentioning

confidence: 99%

Innovative Biomaterials for Bone Tumor Treatment and Regeneration: Tackling Postoperative Challenges and Charting the Path Forward

Wang,

Zhang,

Qiang

et al. 2024

Adv Healthcare Materials

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Surgical resection of bone tumors is the primary approach employed in the treatment of bone cancer. Simultaneously, perioperative interventions, particularly postoperative adjuvant anticancer strategies, play a crucial role in achieving satisfactory therapeutic outcomes. However, the occurrence of postoperative bone tumor recurrence, metastasis, extensive bone defects, and infection are significant risks that can result in unfavorable prognoses or even treatment failure. In recent years, there has been significant progress in the development of biomaterials, leading to the emergence of new treatment options for bone tumor therapy and bone regeneration. This progress report aims to comprehensively analyze the strategic development of unique therapeutic biomaterials with inherent healing properties and bioactive capabilities for bone tissue regeneration. These composite biomaterials, classified into metallic, inorganic non‐metallic, and organic types, are thoroughly investigated for their responses to external stimuli such as light or magnetic fields, internal interventions including chemotherapy or catalytic therapy, and combination therapy, as well as their role in bone regeneration. Additionally, we provide an overview of self‐healing materials for osteogenesis and explore their potential applications in combating osteosarcoma and promoting bone formation. Furthermore, we address the safety concerns of integrated materials and current limitations, while also discussing the challenges and future prospects.This article is protected by copyright. All rights reserved

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Effect of implant formation on drug release kinetics of in situ forming implants

Cited by 30 publications

References 30 publications

In Situ Forming, Enzyme-Responsive Peptoid-Peptide Hydrogels: An Advanced Long-Acting Injectable Drug Delivery System

In Situ Forming, Enzyme-Responsive Peptoid-Peptide Hydrogels: An Advanced Long-Acting Injectable Drug Delivery System

Methodological Considerations in Development of UV Imaging for Characterization of Intra-Tumoral Injectables Using cAMP as a Model Substance

Innovative Biomaterials for Bone Tumor Treatment and Regeneration: Tackling Postoperative Challenges and Charting the Path Forward

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