Long-term delivery of protein therapeutics

Abstract

Introduction Proteins are effective biotherapetics with applications in diverse ailments. Despite being specific and potent, their full clinical potential has not yet been realized. This can be attributed to short half-lives, complex structures, poor in vivo stability, low permeability frequent parenteral administrations and poor adherence to treatment in chronic diseases. A sustained release system, providing controlled release of proteins, may overcome many of these limitations. Areas covered This review focuses on recent development in approaches, especially polymer-based formulations, which can provide therapeutic levels of proteins over extended periods. Advances in particulate, gel based formulations and novel approaches for extended protein delivery are discussed. Emphasis is placed on dosage form, method of preparation, mechanism of release and stability of biotherapeutics. Expert opinion Substantial advancements have been made in the field of extended protein delivery via various polymer-based formulations over last decade despite the unique delivery-related challenges posed by protein biologics. A number of injectable sustained-release formulations have reached market. However, therapeutic application of proteins is still hampered by delivery related issues. A large number of protein molecules are under clinical trials and hence there is an urgent need to develop new methods to deliver these highly potent biologics.

Alpha crystallins in the retinal pigment epithelium and implications for the pathogenesis and treatment of age-related macular degeneration

“…Peptides are involved in modulating various cell functions. These peptides could be more effective than recombinant proteins as potential drugs because of the following features: (1) smaller size, (2) easy to synthesize, optimize and evaluate, (3) no adverse immune responses, (4) easily enter the cells, and (5) perform the same functions [95]. We showed recently that a19-mer peptide from αA crystallin (DFVIFLDVKHFSPEDLTVK) and a 20-mer peptide from αB crystallin (DRFSVNLDVKHFSPEELKVK) exhibited antiapoptotic properties in primary human RPE cells [83] (Figure 6A, B).…”

Reversible hydrophobic ion-paring complex strategy to minimize acylation of octreotide during long-term delivery from PLGA microparticles

“…There has been a substantial rise in the number of protein and peptide biologics in clinical trials for various diseases (Vaishya et al, 2014; Vaishya and Mitra, 2014). Recent advancements in protein engineering allow for rapid development of new peptide/protein therapeutics along with improved understanding of pharmacokinetics and pharmacodynamics.…”

“…Unfortunately, most therapeutic proteins/peptides do not possess the physicochemical characteristics of an ideal drug candidate, such as lipophilicity and permeability (Mitragotri et al, 2014). Biotherapeutics suffer from a myriad of delivery-related issues, such as short half-life, poor bioavailability, low permeability across biological membranes and stability due to hydrophilicity and high molecular weight (Vaishya et al, 2014). Short half-life requires frequent parenteral administrations, which are not patient compliment.…”

Biosynthetic Polymers as Functional Materials

“…Notable are biomimetic polymeric hydrogels containing heparin, hyaluronic acid, and collagen; other native moieties have been used as biotherapeutic storage and release matrices with less impressive stabilization results. 138,139 …”