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Polymeric carriers enhance targeted drug delivery by increasing efficacy while minimizing off-target effects. These carriers comprise a biodegradable polymeric backbone integrated with functional elements that enable targeting, improve physicochemical properties, and regulate drug release.Targeting MechanismsThe targeting ability of polymeric carriers is mediated by a homing device, which is a molecular recognition component designed to selectively bind to specific tissues or cells. Monoclonal...
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Parenteral drug delivery systems play a crucial role in modern therapeutics by enabling the direct administration of drugs into the systemic circulation, bypassing the gastrointestinal tract. These systems are particularly valuable for poorly absorbed oral medications that are unstable in the digestive environment or require rapid onset or sustained therapeutic levels. Delivery is achieved through intravenous, intramuscular, or subcutaneous routes, each selected based on the drug's properties...
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Transdermal drug delivery systems (TDDS) enable the controlled release of drugs across the skin into systemic circulation. They are particularly advantageous for drugs with short half-lives or narrow therapeutic indices, as they maintain consistent plasma concentrations and reduce the risk of subtherapeutic or toxic levels.TDDS are categorized into monolithic, reservoir, and mixed systems. Monolithic systems embed the drug in a polymer matrix, where diffusion governs release. Reservoir systems...
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Site-targeted drug delivery systems enhance therapeutic efficacy while minimizing systemic toxicity and treatment costs. Unlike conventional methods, these systems ensure precise drug delivery, improving bioavailability and reducing side effects. Targeted drug delivery is classified into three levels. First-order targeting directs drugs to the capillary beds of specific organs or tissues. Second-order targets specific cell types, such as tumor cells, using receptor-mediated interactions.
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Modified-release (MR) dosage forms are designed to extend drug release over time, thereby maintaining stable plasma concentrations and reducing dosing frequency. However, their bioavailability is typically below 100% due to incomplete drug release and presystemic metabolism, and limitations in drug permeability across the gastrointestinal epithelium, all of which can restrict the fraction of the drug reaching systemic circulation. Consequently, studying the in vivo bioavailability of MR...
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Rate-programmed drug delivery systems release drugs in a controlled manner to maintain therapeutic levels. Three main designs include reservoir, matrix, and hybrid systems.Reservoir systems consist of a drug core enclosed within a membrane that controls drug release. In non-swelling reservoir systems, polymers like ethyl cellulose or polymethacrylates are used. These do not hydrate in aqueous media and control release through membrane thickness, porosity, or insolubility. This type includes...
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From molecule to absorption: a multiscale framework for subcutaneous biologic delivery.

Mario de Lucio1, Vivek Sree1, Galen Shi1

  • 1Eli Lilly and Company, Indianapolis, IN, USA.

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Summary
This summary is machine-generated.

Subcutaneous injection of monoclonal antibodies (mAbs) faces challenges due to coupled drug, device, and tissue interactions. The Drug-Device-Container-Tissue framework reveals cross-interface dynamics as key to optimizing delivery.

Keywords:
AutoinjectorComputational modelingLymphatic uptakeMonoclonal antibodiesSubcutaneous injection

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Area of Science:

  • Biopharmaceutical formulation and delivery science.
  • Biomaterials and drug delivery engineering.
  • Pharmacokinetics and drug absorption.

Background:

  • Subcutaneous (SC) injection is preferred for self-administered monoclonal antibodies (mAbs).
  • Consistent bioavailability is challenging due to complex interactions across scales.
  • Optimizing individual components yields limited improvements.

Purpose of the Study:

  • Introduce the Drug-Device-Container-Tissue (DDCT) framework for a unified, multiscale analysis.
  • Trace the journey of mAbs from storage through injection to lymphatic absorption.
  • Identify critical bottlenecks for optimizing SC delivery.

Main Methods:

  • Synthesize findings from molecular dynamics simulations.
  • Utilize rheological measurements and high-speed imaging.
  • Employ poromechanical modeling for tissue response analysis.

Main Results:

  • Antibody self-association affects viscosity, diffusion, injectability, and tissue transport.
  • Device actuation can cause instability (sloshing, cavitation, shear); mitigation strategies exist.
  • Injection parameters and tissue heterogeneity critically influence delivery reliability and absorption kinetics.

Conclusions:

  • The DDCT framework highlights cross-interface interactions as the primary bottleneck.
  • This framework enables rational design of next-generation autoinjectors and formulations.
  • Predictive computational tools can be developed based on these multiscale principles.