Related Experiment Video
Updated: Jul 2, 2026
07:20
Discovery and Synthesis Optimization of Isoreticular Al(III) Phosphonate-Based Metal-Organic Framework Compounds Using High-Throughput Methods
Published on: October 6, 2023
Next-generation strategies for PROTAC formulation: mechanistic insights and advanced formulation technologies
Azad Kumar Maurya1, Luis Padrela2,3, Ashish K Agrawal1
1Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology (BHU), Varanasi, India.
Expert Opinion on Drug Delivery
|June 30, 2026
Summary
Proteolysis-targeting chimeras (PROTACs) offer a novel way to degrade disease proteins using the ubiquitin-proteasome system. This review covers PROTAC development, challenges, and strategies for clinical translation.
Area of Science:
- Biochemistry
- Pharmacology
- Drug Development
Background:
- Proteolysis-targeting chimeras (PROTACs) leverage the ubiquitin-proteasome system for selective protein degradation.
- PROTACs offer advantages over other targeted protein degradation (TPD) techniques like LYTAC, AUTAC, and AbTAC.
- Emerging TPD technologies are expanding therapeutic options beyond traditional inhibition.
Purpose of the Study:
- To review the development and mechanism of PROTACs in targeted protein degradation.
- To examine physicochemical and pharmacokinetic challenges hindering PROTAC clinical translation.
- To summarize advanced formulation strategies and characterization techniques for PROTAC therapeutics.
Main Methods:
- Literature review of articles from PubMed, Scopus, and Web of Science up to 2026.
- Analysis of PROTAC mechanism of action via the ubiquitin-proteasome system.
- Examination of formulation strategies (nanoformulations, solid dispersions, prodrugs) and characterization techniques.
Main Results:
- PROTACs enable selective protein degradation, offering a transformative therapeutic approach.
- Physicochemical and pharmacokinetic challenges impact clinical translation.
- Advanced formulations and prodrug strategies can enhance solubility, bioavailability, and efficacy.
Conclusions:
- Future PROTAC research should prioritize bioavailability, targeted delivery, and stability.
- Advancements in prodrugs, E3 ligase selectivity, and oral formulations are crucial.
- Scalable manufacturing, regulatory clarity, and integration with other TPD technologies are essential for clinical success.
Related Concept Videos
01:22Biopharmaceutical Factors Influencing Drug Product Design: Overview
Rational drug product design integrates knowledge of the drug’s physicochemical properties, formulation components, manufacturing techniques, and intended route of administration. Each factor influences the drug’s performance, including how it is released, absorbed, and eliminated in the body.The physicochemical properties of a drug—such as solubility, stability, and particle size—affect its compatibility with excipients and the choice of dosage form. Excipients, though pharmacologically...
01:05Bioavailability Enhancement: Drug Stability Enhancement and GI Retention
Improving a drug's stability in the gastrointestinal (GI) tract is paramount for enhancing its bioavailability and therapeutic effectiveness. Various strategies are employed to protect the drug from the harsh gastric milieu and to ensure its release and absorption at the desired site within the GI tract.Polymer coatings are one such method used to shield drugs from the stomach's acidic environment. By preventing premature drug release, these coatings improve the bioavailability of unstable...
01:24Site-Targeted Drug Delivery Systems: Polymeric Carriers
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...
01:27Pharmaceutical Alternatives: Polymorphic Form-Related and Particle Size-Related Therapeutic Nonequivalence
Changes in polymorphic forms can significantly influence the bioavailability of poorly soluble drugs. Although the FDA defines pharmaceutical equivalence based on having the same active ingredient, dosage form, and route of administration, it does not automatically disqualify products with different polymorphic forms. This means two products with different polymorphs can still be deemed pharmaceutically equivalent. However, polymorphic differences can affect properties like wettability,...
01:18Formulation and Manufacturing Process: Physical Attributes of Generic Tablets and Capsules
Bioequivalence in generic drugs, such as tablets and capsules, refers to their pharmaceutical equivalence to the brand-name counterparts. However, for therapeutic equivalence, manufacturers must also consider physical attributes like size, shape, and weight (FDA Guidance for Industry, December 2003). Discrepancies in these aspects could impact patient compliance and cause medication errors. For instance, swallowing difficulties, often experienced with larger tablets or capsules, can lead to...
01:19Modified-Release Drug Delivery Systems: Overview
Modified-release dosage forms are designed to address the limitations of drugs with short biological half-lives. These forms maintain stable therapeutic drug concentrations over extended periods, reducing the need for frequent dosing. A consistent drug level helps minimize peak-trough fluctuations, which can reduce adverse effects, lower the risk of drug resistance, and improve overall treatment effectiveness.One common type of modified-release form is the extended-release (ER) formulation. ER...