Advances and Opportunities in Delivery of Therapeutic Proteins and Peptides

Banakar, Umesh V.

doi:10.1177/088532829701100402

Cited by 16 publications

(9 citation statements)

References 84 publications

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“…Incorporation of proteins and peptides into the liposomal formulation helps to circumvent these limitations. Most of the phospholipids used in the formation of liposomes are biocompatible and protect encapsulated peptide/proteins from the inactivating effects of aggregation during storage or any other physical inactivation during product handling before administration to the patient without any added adverse effects 5, 135. The ampiphillic nature of phospholipids, more specifically the subsequent formation of an aqueous core and hydrophobic bilayer, make them suitable for use with protein therapeutics displaying a wide variety of biophysical characteristics 133.…”

Section: Lipid Drug Deliverymentioning

confidence: 99%

“…In contrast to modifying the protein structure, covalent chemical attachment of compounds such as poly(ethylene glycol) (PEG) or polysialic acid (PSA) to therapeutic protein represent a relatively new approach. Drug formulation systems, such as liposomes, polymeric microspheres, and polymeric nanoparticles, are another means to help overcome the current limitations of protein therapeutics 4, 5…”

Section: Introductionmentioning

confidence: 99%

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Delivery of Therapeutic Proteins

Pisal

Kosloski

Balu‐Iyer

2010

Journal of Pharmaceutical Sciences

483

386

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The safety and efficacy of protein therapeutics are limited by three interrelated pharmaceutical issues, in vitro and in vivo instability, immunogenicity and shorter half-lives. Novel drug modifications for overcoming these issues are under investigation and include covalent attachment of poly(ethylene glycol) (PEG), polysialic acid, or glycolic acid, as well as developing new formulations containing nanoparticulate or colloidal systems (e.g. liposomes, polymeric microspheres, polymeric nanoparticles). Such strategies have the potential to develop as next generation protein therapeutics. This review includes a general discussion on these delivery approaches. KeywordsProtein delivery; PEGylation; Liposomes; hyperglycosylation; Poly(lactic/glycolic) acid INTRODUCTIONSince the late 20 th century numerous therapeutic proteins and peptides have emerged in the market. PHARMA 2010 reported that biotech products accounted for more than 35% of the 37 new active substances launched in 2001.1 In 2007, global biotech drug sales grew at twice the rate of traditional small molecule drugs (12.5% vs 6.4%) with total revenues of $75 billion US. Biotech drugs accounted for one fifth of all blockbuster drugs in the market as of 2008.2 From a therapeutic perspective, proteins offer the distinct advantage of specific mechanisms of action and are highly potent. Despite these advantages, biotech products must overcome the hurdles posed by high molecular weight, short half-lives, instability, and immunogenicity. Several strategies have been evaluated in an effort to improve the current limitations of therapeutic peptides and proteins in the creation of so called "second generation" protein therapeutics. Most efforts center around one of two approaches-either a change in the agent itself (e.g. mutations in protein structure or covalent attachment of moieties) or by a change in formulation.3 In contrast to modifying the protein structure, covalent chemical attachment of compounds such as poly(ethylene glycol) (PEG) or polysialic acid (PSA) to therapeutic protein represent a relatively new approach. Drug formulation systems, such as liposomes, polymeric microspheres, and polymeric nanoparticles, are another means to help overcome the current limitations of protein therapeutics.4 , 5The intent of this review is to provide a general discussion of approaches being applied to improve safety and efficacy of protein therapeutics. This includes the areas of PEGylation, PEGYLATIONThe conjugation of polymers to proteins had been in practice since the 1950s, but it was the development of PEGylation that provided the real breakthrough in enhancing the pharmaceutical properties of proteins and peptides in a viable manner 6 PEGylation, the covalent attachment of PEG moieties to a therapeutic agent, was first reported in the 1970s. 7,8 Experiments attempting to improve delivery aspects via PEGylation found not only the intended benefits, but overall enhancement of stability, pharmacokinetics, and therapeutic utility of molecules. [9][10][11][1...

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Section: Lipid Drug Deliverymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Delivery of Therapeutic Proteins

Pisal

Kosloski

Balu‐Iyer

2010

Journal of Pharmaceutical Sciences

483

386

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“…Poly(lactic‐co‐glycolic acid) (PLGA) is one of the most commonly used synthetic polymers for tissue engineering and drug/protein delivery (Banakar, ). Advantages of PLGA include the ability to alter the polymer's mechanical properties, rate of degradation, and drug release kinetics by controlling factors such as co‐polymer composition (ratio of lactic acid to glycolic acid), end group chemistry (acid or aliphatic end cap), molecular weight, and crystallinity (Jain, ; Giteau et al ., ).…”

Section: Introductionmentioning

confidence: 99%

Treatment of growth plate injury using IGF-I-loaded PLGA scaffolds

Sundararaj

Cieply

Gupta

et al. 2012

J Tissue Eng Regen Med

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Growth plate fracture can lead to retarded growth and unequal limb length, which may have a lifelong effect on a person's physical stature. The goal of this research was to develop an in vivo tissue-engineering approach for the treatment of growth plate injury via localized delivery of insulin-like growth factor I (IGF-I) from cell-free poly(lactic-co-glycolic acid) (PLGA) scaffolds. Mass loss and drug release studies were conducted to study the scaffold degradation and IGF-I release patterns. In vitro cell studies showed that rat bone marrow stromal cells seeded on the porous scaffolds colonized the pores and deposited matrix within the scaffolds. These in vitro evaluations were followed by a proof-of-concept animal study involving implantation of scaffolds in proximal tibial growth plate defects in New Zealand white rabbits. Histological analysis of tissue sections from the in vivo studies showed regeneration of cartilage, albeit with disorganized structure, at the site of implantation of IGF-I-releasing scaffolds; in contrast, only bone was formed in empty defects and those treated with IGF-free scaffolds. The present findings show the potential for treating growth plate injury using in vivo tissue engineering techniques.

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“…Among them, two strategies are frequently being employed: one is the change in the therapeutic protein (development through the alteration in protein configuration or covalent add-on) itself and through development in the formulation [29, 30]. Proteins are generally conjugated with natural or synthetic polymers (PEGylation, HESylation, and polysialylation) to alter structure of therapeutic proteins [31, 32]. Conversely, different drug formulation systems are also being used to overcome the existing limitations of therapeutic proteins.…”

Section: General Strategies For Therapeutic Protein or Gene Delivementioning

confidence: 99%

Next Generation Delivery System for Proteins and Genes of Therapeutic Purpose: Why and How?

Sharma

Kundu

Nam

et al. 2014

BioMed Research International

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Proteins and genes of therapeutic interests in conjunction with different delivery systems are growing towards new heights. “Next generation delivery systems” may provide more efficient platform for delivery of proteins and genes. In the present review, snapshots about the benefits of proteins or gene therapy, general procedures for therapeutic protein or gene delivery system, and different next generation delivery system such as liposome, PEGylation, HESylation, and nanoparticle based delivery have been depicted with their detailed explanation.

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Advances and Opportunities in Delivery of Therapeutic Proteins and Peptides

Cited by 16 publications

References 84 publications

Delivery of Therapeutic Proteins

Delivery of Therapeutic Proteins

Treatment of growth plate injury using IGF-I-loaded PLGA scaffolds

Next Generation Delivery System for Proteins and Genes of Therapeutic Purpose: Why and How?

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