𝐈𝐧𝐭𝐚𝐯𝐢𝐬 𝐑𝐞𝐬𝐞𝐚𝐫𝐜𝐡 𝐑𝐨𝐮𝐧𝐝𝐮𝐩
"𝐒𝐭𝐫𝐚𝐭𝐞𝐠𝐢𝐜 𝐀𝐩𝐩𝐫𝐨𝐚𝐜𝐡𝐞𝐬 𝐭𝐨 𝐈𝐦𝐩𝐫𝐨𝐯𝐢𝐬𝐞 𝐏𝐞𝐩𝐭𝐢𝐝𝐞 𝐃𝐫𝐮𝐠𝐬 𝐚𝐬 𝐍𝐞𝐱𝐭 𝐆𝐞𝐧𝐞𝐫𝐚𝐭𝐢𝐨𝐧 𝐓𝐡𝐞𝐫𝐚𝐩𝐞𝐮𝐭𝐢𝐜𝐬"
𝐖𝐡𝐚𝐭 𝐚𝐫𝐞 𝐭𝐡𝐞 𝐦𝐚𝐢𝐧 𝐜𝐡𝐚𝐥𝐥𝐞𝐧𝐠𝐞𝐬 𝐢𝐧 𝐝𝐞𝐯𝐞𝐥𝐨𝐩𝐢𝐧𝐠 𝐩𝐞𝐩𝐭𝐢𝐝𝐞-𝐛𝐚𝐬𝐞𝐝 𝐭𝐡𝐞𝐫𝐚𝐩𝐞𝐮𝐭𝐢𝐜𝐬, 𝐚𝐧𝐝 𝐡𝐨𝐰 𝐜𝐚𝐧 𝐭𝐡𝐞𝐬𝐞 𝐛𝐞 𝐚𝐝𝐝𝐫𝐞𝐬𝐬𝐞𝐝?
Peptide-based therapeutics face several challenges, including susceptibility to proteolytic degradation, poor membrane permeability, short half-life, and limited oral bioavailability, which limit their clinical efficacy. To address these issues, researchers have developed a variety of chemical modifications such as backbone modifications, which enhance the stability of peptide bonds, and side-chain modifications to improve peptide-receptor interactions and specificity. Termini protection, like N-terminal acetylation or C-terminal amidation, helps prevent enzymatic degradation. PEGylation and glycosylation are used to increase molecular size, reduce renal clearance, and enhance half-life. Cyclization is also employed to stabilize the peptide structure, reducing flexibility and improving resistance to proteolytic enzymes. These strategies collectively aim to improve the pharmacokinetics and therapeutic potential of peptide drugs.
𝐇𝐨𝐰 𝐚𝐫𝐞 𝐩𝐞𝐩𝐭𝐢𝐝𝐞-𝐛𝐚𝐬𝐞𝐝 𝐝𝐫𝐮𝐠𝐬 𝐛𝐞𝐢𝐧𝐠 𝐚𝐝𝐯𝐚𝐧𝐜𝐞𝐝 𝐟𝐨𝐫 𝐜𝐥𝐢𝐧𝐢𝐜𝐚𝐥 𝐮𝐬𝐞, 𝐚𝐧𝐝 𝐰𝐡𝐚𝐭 𝐫𝐨𝐥𝐞 𝐝𝐨𝐞𝐬 𝐝𝐫𝐮𝐠 𝐝𝐞𝐥𝐢𝐯𝐞𝐫𝐲 𝐩𝐥𝐚𝐲 𝐢𝐧 𝐭𝐡𝐢𝐬 𝐩𝐫𝐨𝐜𝐞𝐬𝐬?
Peptide-based drugs are being advanced through both chemical modifications and computational methods that optimize their design for clinical use. Computational tools aid in predicting peptide structure, stability, and interaction with biological targets, allowing for the design of more effective and stable peptides. In terms of drug delivery, innovative approaches like nanoparticle-based systems, such as liposomes and micelles, protect peptides from degradation and ensure targeted delivery. These systems enhance the bioavailability of peptides by improving their absorption through routes such as transdermal, oral, pulmonary, and nasal delivery. Nanocarriers further facilitate sustained release, enabling lower dosages and reduced side effects, which are critical for improving the clinical application of peptide-based therapies.
Paper reference: Barman, P., Joshi, S., Sharma, S., Preet, S., Sharma, S., & Saini, A. (2023). Strategic approaches to improvise peptide drugs as next generation therapeutics. International journal of peptide research and therapeutics, 29(4), 61.
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