Prodrug approach: An overview of recent cases

Abet, Valentina; Filace, Fabiana; Recio, Javier; Alvárez‐Builla, Julio; Burgos, Carolina

doi:10.1016/j.ejmech.2016.10.061

Cited by 137 publications

(68 citation statements)

References 74 publications

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“…Since prodrugs provide a versatile approach to improve the clinical usefulness of many therapeutic agents by improving water solubility and permeability, sustained release, drug targeting, and the metabolic stability of the parent drug, prodrug design should be considered at the early stages of preclinical development. [36][37][38][39] Amino acid prodrugs have been illustrated to significantly improve the oral delivery of drugs that have poor solubility and permeability (e.g., valacyclovir and valganciclovir). 40,41 More importantly, the diversity of amino acids offers a great opportunity to finely tune the amphiphilicity of drugs, thus altering their self-assembly behavior in aqueous solution to generate various nanostructures (e.g., nanotubes, nanospheres, and nanofibers).…”

Section: Dex-sa-fffe Nanoparticle Formation and Characterizationmentioning

confidence: 99%

High drug payload nanoparticles formed from dexamethasone-peptide conjugates for the treatment of endotoxin-induced uveitis in rabbit

Yu¹,

Zhang²,

Lei³

et al. 2019

IJN

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PurposeTo develop and demonstrate the effectiveness of a novel dexamethasone (Dex) nanoformulation for treating uveitis.Materials and methodsWe designed and screened a dexamethasone-peptide conjugate (Dex-SA-FFFE), formed via a biodegradable ester bond linkage, that could spontaneously form high drug payload nanoparticles in aqueous solution for treating uveitis.ResultsAn in vitro release study indicated that Dex and Dex-SA-FFFE sustainably released from Dex-SA-FFFE nanoparticles over a 48 h study period. Meanwhile, the formed Dex-SA-FFFE nanoparticles hardly caused cytotoxicity in human corneal epithelial cell at drug concentrations up to 1 mM after 24 h of incubation but reduced cell viability after 48 h and 72 h of incubation. An in vitro anti-inflammatory efficacy assay showed that the Dex-SA-FFFE nanoparticles exhibited a comparable anti-inflammatory efficacy to that of Dex in lipopolysaccharide (LPS)-activated RAW264.7 macrophages via significant decreases in the secretion of various pro-inflammatory cytokines (e.g., nitric oxide, tumor necrosis factor-α, interleukin-6). Topical instillation of Dex-SA-FFFE nanoparticles showed good ocular tolerance without causing changes in corneal thickness and intraocular pressure during the entire study period. Furthermore, topical instillation of Dex-SA-FFFE nanoparticles displayed a comparable in vivo therapeutic efficacy to that of dexamethasone sodium phosphate (Dexp) aqueous solutions in an endotoxin-induced uveitis (EIU) rabbit model.ConclusionBased on these results, it is reasonable to believe that the proposed Dex-SA-FFFE nanoparticles might have great application for the treatment of anterior uveitis.

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Section: Dex-sa-fffe Nanoparticle Formation and Characterizationmentioning

confidence: 99%

High drug payload nanoparticles formed from dexamethasone-peptide conjugates for the treatment of endotoxin-induced uveitis in rabbit

Yu¹,

Zhang²,

Lei³

et al. 2019

IJN

View full text Add to dashboard Cite

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“…So prodrug can be defined as inactive form that undergoes biotransformation and converted to active form to elicit its pharmacological effect. Development of prodrug depends on specific property of drug that needs improvement and mostly with respect to stability, improving bioavailability [2].…”

Section: Prodrugmentioning

confidence: 99%

Preformulation Studies: An Integral Part of Formulation Design

Patel¹

2020

Pharmaceutical Formulation Design - Recent Practices

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When a promising new chemical entity is synthesized, it needs transformation to appropriate formulation in order to show a better and desirable action at appropriate site. Preformulation study is a phase which is initiated once the new molecule is seeded. In a broader way, it deals with studies of physical, chemical, analytical, and pharmaceutical properties related to molecule and provides idea about suitable modification in molecule to show a better performance. Study of these parameters and suitable molecular modification can be linked to generation of effective, safer, stable, and reliable pharmaceutical formulation. Therefore, preformulation study is an approach for generation of pharmaceutical formulation which utilizes knowledge and area application of toxicology, biochemistry, medicinal chemistry, and analytical chemistry. The highlighted chapter is framed with a vision to provide an in-depth knowledge about pharmaceutical formulation development.

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“…Prodrugs are inactive forms of therapeutic molecules produced via the chemical modification of the original molecule, which turns into the active form of the molecule during administration, commonly by the effect of enzymatic reactions or other possible reactions inside the body [7]. The primary goals of the prodrug approach can be outlined as follows: targeted release, ameliorating absorption or membrane permeability and decreasing metabolism or side effects [87]. The generation of prodrugs from proteins/peptides appears to be an attractive approach concerning the improvement and optimization of their delivery because all the basic objectives of this approach may be fulfilled with the modification of the structure of biopharmaceuticals [88].…”

Section: Prodrug Approachmentioning

confidence: 99%

Review of recently used techniques and materials to improve the efficiency of orally administered proteins/peptides

et al. 2019

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Objectives The main objective of present review is to explore and evaluate the effectiveness of recently developed methods to improve the bioavailability of orally administered biopharmaceutical drugs. Methods A systematic search of sciencedirect, tandfonline and Google Scholar databases based on various sets of keywords was performed. All results were evaluated based on their abstracts, and irrelevant studies were neglected during further evaluation. Results At present, biopharmaceuticals are used as injectable therapies as they are not absorbed adequately from the different routes of drug administration, particularly the oral one. Their insufficient absorption is attributed to their high molecular weight, degradation by proteolytic enzymes, high hydrophilicity and rigidity of the absorptive tissues. From industrial aspect incorporation of enzyme inhibitors (EIs) and permeation enhancers (PEs) and mucoadhesive polymers into conventional dosage forms may be the easiest way of formulation of orally administered macromolecular drugs, but the effectiveness of protection and absorption enhancement here is the most questionable. Conjugation may be problematic from regulatory aspect. Encapsulation into lipid-based vesicles sufficiently protects the incorporated macromolecule and improves intestinal uptake but have considerable stability issues. In contrast, polymeric nanocarriers may provide good stability but provides lower internalization efficacy in comparison with the lipid-based carriers. Conclusion It can be concluded that the combination of the advantages of mucoadhesive polymeric and lid-based carriers in hybrid lipid/polymer nanoparticles may result in improved absorption and might represent a potential means for the oral administration of therapeutic proteins in the near future.

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Prodrug approach: An overview of recent cases

Cited by 137 publications

References 74 publications

High drug payload nanoparticles formed from dexamethasone-peptide conjugates for the treatment of endotoxin-induced uveitis in rabbit

High drug payload nanoparticles formed from dexamethasone-peptide conjugates for the treatment of endotoxin-induced uveitis in rabbit

Preformulation Studies: An Integral Part of Formulation Design

Review of recently used techniques and materials to improve the efficiency of orally administered proteins/peptides

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