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Related Concept Videos

Phase II Reactions: Acetylation Reactions01:24

Phase II Reactions: Acetylation Reactions

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Acetylation, a phase II biotransformation reaction, introduces an acetyl group to drugs or their metabolites. Acetyltransferase enzymes facilitate this reaction, which resembles α-amino acid conjugation due to the addition of a functional group to the drug molecule.
The substrates for acetylation are typically drugs or their metabolites with an amino, sulfonamide, or hydrazine functional group. Acetylation can occur at several points in the drug molecule, including primary, secondary, and...
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Modification of secretory and transmembrane proteins entering the rough ER begins in the ER lumen. These modifications aid in protein folding and stabilize the acquired tertiary structure. Protein modifications in the rough ER co-occur at different stages of protein folding.
Broadly, these modifications can be categorized into four main categories — glycosylation, formation of disulfide bonds, assembly of protein subunits, and specific proteolytic cleavages like removal of signal...
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Phase II Reactions: Sulfation and Conjugation with α-Amino Acids01:19

Phase II Reactions: Sulfation and Conjugation with α-Amino Acids

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Sulfation and α-amino acid conjugation are two critical biotransformation reactions in drug metabolism. Sulfation, a phase II biotransformation reaction, involves adding a polar sulfate group to a drug, enhancing its water solubility and promoting excretion. This process can either co-occur with or occur independently of glucuronidation. Nonmicrosomal sulfotransferase enzymes catalyze the process. The reaction involves 3'-phosphoadenosine-5'-phosphosulfate or PAPS coenzyme...
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Phase II Reactions: Glucuronidation01:24

Phase II Reactions: Glucuronidation

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Glucuronidation, a pivotal phase II biotransformation process, involves the coupling of glucuronic acid to a drug or xenobiotic. Given its widespread occurrence and critical role in drug metabolism, it's considered the most crucial phase II reaction. It enhances the water solubility of substances, aiding their expulsion from the body. The driving force behind these reactions is a group of enzymes known as UDP-glucuronosyltransferases (UGTs). UGTs facilitate the transfer of a glucuronic acid...
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Hydrolysis of acid halides is a nucleophilic acyl substitution reaction in which acid halides react with water to give carboxylic acids. The reaction occurs readily and does not require acid or a base catalyst.
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Drug Metabolism: Phase II Reactions01:14

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Phase II reactions are essential for the detoxification and elimination of drugs from the body. These reactions involve the conjugation of parent drugs or their phase I metabolites with endogenous molecules, resulting in more hydrophilic drug conjugates. The primary conjugation reactions in this phase are sulfation and glucuronidation. Both sulfation and glucuronidation typically produce biologically inactive metabolites. However, in some cases involving prodrugs, active metabolites may be...
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Modification and Functionalization of the Guanidine Group by Tailor-made Precursors
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Glycyrrhizic acid modified

Qi Chen1, Chengyuan Wu2, Siwei Wang2

  • 1Faculty of Chinese Medicine, Macau University of Science and Technology, Macao, China.

Frontiers in Chemistry
|June 8, 2023
PubMed
Summary
This summary is machine-generated.

This study developed novel soluble microneedles combining glycyrrhizic acid and methotrexate on carbon dots for rheumatoid arthritis treatment. These microneedles effectively reduced inflammation and showed therapeutic effects in animal models.

Keywords:
Poria cocos polysaccharidecarbon dotsglycyrrhizic acidmethotrexatemicroneedlesrheumatoid arthritis

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Area of Science:

  • Biomaterials Science
  • Nanotechnology
  • Rheumatology

Background:

  • Rheumatoid arthritis (RA) is a chronic autoimmune joint disease.
  • Oral methotrexate is effective but limited by adverse reactions.
  • Transdermal drug delivery offers an alternative, but combination therapies in microneedles are underexplored.

Purpose of the Study:

  • To develop a novel nano-drug delivery system for transdermal treatment of RA.
  • To create biodegradable soluble microneedles for enhanced drug delivery.
  • To investigate the combined anti-inflammatory effects of glycyrrhizic acid and methotrexate.

Main Methods:

  • Modified carbon dots with glycyrrhizic acid and loaded with methotrexate.
  • Fabricated hyaluronic acid-based soluble microneedles containing the nano-drug delivery system.
  • Characterized the nano-drug delivery system and microneedles using various analytical techniques.
  • Evaluated in vitro anti-inflammatory effects on macrophage models and in vivo therapeutic efficacy in a rat RA model.

Main Results:

  • Successfully synthesized and characterized glycyrrhizic acid-carbon dots-methotrexate nano-drug delivery system with 49.09% methotrexate loading.
  • Demonstrated potent inhibition of pro-inflammatory cytokine secretion by macrophages in vitro.
  • Showed significant therapeutic effects in a rat model of rheumatoid arthritis, reducing inflammation.

Conclusions:

  • The developed glycyrrhizic acid-carbon dots-methotrexate soluble microneedles represent a promising transdermal delivery system for RA.
  • This approach offers a feasible strategy to overcome oral methotrexate limitations and enhance RA treatment efficacy.