The pharmaceutics and delivery of therapeutic polypeptides and proteins

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Abstract

Proteins and peptides with immunoregulatory properties are a rapidly growing class of pharmacophores for a wide variety of indications in a number of clinical disciplines. Despite the rapid development of these new drugs, they retain severe pharmacologic deficiencies due to their rapid degradation and elimination. This results in their administration at superpharmacological doses and subsequent clinical toxicity. Further, because these compounds often act indirectly, their clinical development path is less obvious than that of other therapeutics. Thus, their development has become focused on a pharmacologic approach predicated on the preclinical identification of therapeutic surrogates and the subsequent testing of a clinical hypothesis. Immunoregulatory peptides and proteins, including cytokines and growth factors, have been used as single agents and in combinations with one another or other therapeutic modalities. Due to the challenge associated with the targeting and delivery of these therapeutics, novel strategies to achieve the desired therapeutic end-points have been developed. This includes the use of peptide inducers or antagonists as well as delivery strategies via gene and cellular therapy. These therapeutic strategies of the future are in response to the pharmacologic deficiencies of proteins and provide exciting new directions for their development in both the near and long term. This review addresses the pharmacologic deficiencies of proteins, preclinical and clinical developmental strategies, and future strategies based on the use of molecular therapeutics. The primary emphasis has been placed on preclinical and clinical studies of immune and hematopoietic augmenting agents. However, we also discuss proteins that are still in animal models, agents whose profile of activity is associated with the induction of a cytokine cascade and the targeted delivery of a gene via hematopoietic stem cells, lymphocytes, or other autologous tissues or tumors.

Original languageEnglish (US)
Pages (from-to)247-299
Number of pages53
JournalAdvanced Drug Delivery Reviews
Volume10
Issue number2-3
DOIs
Publication statusPublished - Jan 1 1993

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Keywords

  • (Interferon)
  • (Interleukin-2)
  • (colony-stimulating factor)
  • CSF
  • Cytokines
  • IFN
  • IL-2
  • Immunotherapy
  • Pharmacokinetics
  • Proteins

ASJC Scopus subject areas

  • Pharmaceutical Science

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