Nanpparticles for Protein and Peptide Delivery is a group in Biological Sciences on Mendeley.
Cheng, W.-P. et al., 2010. In vitro and in vivo characterisation of a novel peptide delivery system: amphiphilic polyelectrolyte-salmon calcitonin nanocomplexes. Journal of controlled release : official journal of the Controlled Release Society, 147(2), pp.289-97. Available at: http://www.ncbi.nlm.nih.gov/pubmed/20705108 [Accessed March 17, 2012].
Abstract: The cationic peptide, salmon calcitonin (sCT) was complexed with the cationic amphiphilic polyelectrolyte, poly(allyl)amine, grafted with palmitoyl and quaternary ammonium moieties at pH 5.0 and 7.4 to yield particulates (sCT-QPa). The complexes were approximately 200 nm in diameter, had zeta potentials ranging from +20 to +50 mV, and had narrow polydispersity indices (PDIs). Differential scanning calorimetry revealed the presence of an interaction between sCT and QPa in the complexes. Electron microscopy confirmed the zeta-size data and revealed a vesicular bilayer structure with an aqueous core. Tyrosine- and Nile red fluorescence indicated that the complexes retained gross physical stability for up to 7 days, but that the pH 5.0 complexes were more stable. The complexes were more resistant to peptidases, serum and liver homogenates compared to free sCT. In vitro bioactivity was measured by cAMP production in T47D cells and the complexes had EC50 values in the nM range. While free sCT was unable to generate cAMP following storage for 7 days, the complexes retained approximately 33% activity. When the complexes were injected intravenously to rats, free and complexed sCT (pH 5.0 and 7.4) but not QPa reduced serum calcium over 120 min. Free and complexed sCT but not QPa also reduced serum calcium over 240 min following intra-jejunal administration. In conclusion, sCT-QPa nanocomplexes that have been synthesised are stable, bioactive and resistant to a range of peptidases. These enhanced features suggest that they may have the potential for improved efficacy when formulated for injected and oral delivery.
Crombez, L. et al., 2008. Peptide-based nanoparticle for ex vivo and in vivo drug delivery. Current pharmaceutical design, 14(34), pp.3656-65. Available at: http://www.ncbi.nlm.nih.gov/pubmed/19075741 [Accessed April 8, 2012].
Abstract: One of the major challenges for new therapeutics molecules to enter the clinic remains improving their bioavailability and cellular uptake. Therefore, delivery has become a key stone in therapeutic development and several technologies have been designed to improve cellular uptake of therapeutic molecules, including cell-penetrating peptides (CPPs) or protein transduction domain (PTD). PTDs or CPPs were discovered twenty years ago, based on the potency of several proteins to enter cells and nowadays, numerous peptide carriers have been described and successfully applied for ex vivo and in vivo delivery of varying therapeutic molecules. Two CPP-strategies have been reported; the first one requires chemical linkage between the drug and the carrier for cellular drug internalization and the second is based on the formation of stable complexes with drugs depending on their chemical nature. Peptide-Based-Nanoparticle Devices (PBND), correspond to short amphipathic peptides able to form stable nanoparticles with proteins and/or nucleic acids. Three PBND-families, PEP, MPG and CADY have been described, these carriers mainly enter cells independently of the endosomal pathway and efficiently deliver cargoes in a large variety of challenging cell lines as well as in animal models. This review will focus on the structure/function relationship of the PBND: CADY, PEP and MPG, in the general context of drug delivery. It will also highlight the requirement of primary or secondary amphipathic carriers for in vitro and in vivo delivery of therapeutic molecules and provide an update of their pre-clinical evaluation.
Fonseca, S.B., Pereira, M.P. & Kelley, S.O., 2009. Recent advances in the use of cell-penetrating peptides for medical and biological applications. Advanced drug delivery reviews, 61(11), pp.953-64. Available at: http://www.ncbi.nlm.nih.gov/pubmed/19538995 [Accessed March 10, 2012].
Abstract: The selective permeability of the plasma membrane prohibits most exogenous agents from gaining cellular access. Since many therapeutics and reporter molecules must be internalized for activity, crossing the plasma membrane is essential. A very effective class of transporters harnessed for this purpose are cell penetrating peptides (CPPs), a group of short cationic sequences with a remarkable capacity for membrane translocation. Since their discovery in 1988, CPPs have been employed for the delivery of a wide variety of cargo including small molecules, nucleic acids, antibodies and nanoparticles. This review describes recent advances in the use of CPPs for biological and therapeutic applications. In particular, an emphasis is placed on novel systems and insights acquired since 2006. Basic research on CPPs has recently yielded techniques that provide further information on the controversial mechanism of CPP uptake and has also resulted in the development of new model membrane systems to evaluate these mechanisms. In addition, recent use of CPPs for the development of new cellular imaging tools, biosensors, or biomolecular delivery systems have been highlighted. Lastly, novel peptide delivery vectors, designed to tackle some of the drawbacks of CPPs and enhance their versatility, will be described. This review will illustrate the diverse applications for which CPPs have been harnessed and also demonstrate the remarkable advancements these peptides have facilitated in cell biology.
Kim, S.K. & Huang, L., 2012. Nanoparticle delivery of a peptide targeting EGFR signaling. Journal of controlled release : official journal of the Controlled Release Society, 157(2), pp.279-86. Available at: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3229664&tool=pmcentrez&rendertype=abstract [Accessed March 5, 2012].
Abstract: EGFR serves as an important therapeutic target because of its over-expression in many cancers. In this study, we investigated a peptide-based therapy aimed at blocking intracellular protein-protein interactions during EGFR signaling and evaluated a targetable lipid carrier system that can deliver peptides to intracellular targets in human cancer cells. EEEEpYFELV (EV), a nonapeptide mimicking the Y845 site of EGFR which is responsible for STAT5b phosphorylation, was designed to block EGFR downstream signaling. EV was loaded onto LPH nanoparticles that are comprised of a membrane/core structure including a surface-grafted polyethylene glycol (PEG) used to evade the reticuloendothelial system (RES) and anisamide (AA) for targeting the sigma receptor over-expressed in H460 human lung cancer cells. EV formulated with PEGylated and targeted LPH (LPH-PEG-AA) was taken up by the tumor cells and trafficked to the cytoplasm with high efficiency. Using this approach, EV acted as a dominant negative inhibitor of STAT5b phosphorylation, arrested cell proliferation, and induced massive apoptosis. Intravenous administration of EV loaded in LPH-PEG-AA led to efficient EV peptide delivery to the tumor in a xenograft mouse model, and multiple injections inhibited tumor growth in a dose-dependent manner. Our findings offer proof-of-concept for an intracellular peptide-mediated cancer therapy that is delivered by carefully designed nanoparticles.
Kreuter, J. et al., 1995. Passage of peptides through the blood-brain barrier with colloidal polymer particles (nanoparticles). Brain Research, 674(1), pp.171-174. Available at: http://dx.doi.org/10.1016/0006-8993(95)00023-J [Accessed April 8, 2012].
Abstract: Transport of the hexapeptide dalargin across the blood-brain barrier was accomplished using a nanoparticle formulation. The formulation consisted of dalargin bound to poly(butyl cyanoacrylate) nanoparticles by sorption, coated with polysorbate 80. Intravenous injection of this formulation to mice resulted in an anlgesic effect. All controls, including a simple mixture of the three components (drugs, nanoparticles, and surfactant) mixed directly before i.v. injection, exhibited no effect. Analgesia was also prevented by pretreatment with naloxone. Fluorescent and electron microscopic studies indicated that the passage of the particle-bound drug occurred by phagocytic uptake of the polysorbate 80-coated nanoparticles by the brain blood vessel endothelial cells.
Malik, D.K. et al., 2007. Recent advances in protein and peptide drug delivery systems. Current drug delivery, 4(2), pp.141-51. Available at: http://www.ncbi.nlm.nih.gov/pubmed/17456033 [Accessed April 8, 2012].
Abstract: Delivery of therapeutic proteins/peptides has received a considerable amount of attention over the last 10 years, but there are number of limitations to oral delivery of proteins. The barriers to peptide bioavailability after oral administration are intestinal membrane permeability, size, intestinal and hepatic metabolism and lastly solubility. A number of approaches have been used to overcome these limitations. Poor membrane permeabilities of hydrophilic peptides might be overcome by structurally modifying the compound, thus increasing their membrane partition characteristics and their affinity for carrier proteins. Another approach is site specific delivery of the peptides to the most permeable part of the intestine. Metabolism (hepatic and intestinal) of peptides might be controlled by co-administration of competitive enzyme inhibitors, structural modifications and administration of the compound as well as absorbed prodrug that is converted into therapeutically active agent after its absorption. Various delivery systems like prolease technology, nano-particulate and microparticulate delivery system, mucoadhesive delivery of peptides and microspheres have been developed for the delivery of proteins and peptides. Non-conventional delivery systems for proteins are biodegradable and non-biodegradable systems. Besides these, some other approaches for protein and peptide delivery are vector mediated delivery of proteins using adenovirus, macroflux transdermal patches, pulmonary delivery of proteins, delivery of proteins and peptides across blood brain barrier.
Park, J.H. et al., 2004. Self-assembled nanoparticles based on glycol chitosan bearing 5beta-cholanic acid for RGD peptide delivery. Journal of controlled release : official journal of the Controlled Release Society, 95(3), pp.579-88. Available at: http://www.ncbi.nlm.nih.gov/pubmed/15023468 [Accessed March 12, 2012].
Abstract: The synthetic peptide bearing Arg-Gly-Asp (RGD) sequence is considered to specifically bind to alpha(v)beta(3) integrin expressed on endothelial cells in the angiogenic blood vessels, which provides a potential to inhibit the tumor growth. As a carrier for the RGD peptide, hydrophobically modified glycol chitosan (HGC) capable of forming nano-sized self-aggregates was prepared by the chemical conjugation of 5beta-cholanic acid to the main backbone of glycol chitosan. The RGD peptide labeled with fluoresein isothiocyanate (FITC-GRGDS) was loaded into self-aggregates in three different conditions: simple mixing, sonication, and solvent evaporation methods. Of different methods applied, solvent evaporation method showed the most promising results for peptide loading, as judged by the yield (>70%) and loading efficiency (>75%). It was found that the presence of FITC-labeled peptides makes the self-aggregates to be compact, possibly due to the role of both hydrophobic FITC and peptides containing carboxylic acids that allow hydrogen bonding and electrostatic interaction with the primary amino groups in the main backbone of glycol chitosan. FITC-labeled peptides were released from self-aggregates in a physiological solution (pH 7.4) for up to 1 day. From the cell adhesion and migration assays, it was demonstrated that FITC labeling of peptides does not significantly deteriorate biological activity of the parent peptide drug (GRGDS). Overall, the self-aggregates loaded with FITC-GRGDS might be useful for monitoring or destroying the angiogenic vessels surrounding the tumor tissue.
Prego, C. et al., 2006. Chitosan-PEG nanocapsules as new carriers for oral peptide delivery. Effect of chitosan pegylation degree. Journal of controlled release : official journal of the Controlled Release Society, 111(3), pp.299-308. Available at: http://www.ncbi.nlm.nih.gov/pubmed/16481062 [Accessed March 15, 2012].
Abstract: We have previously reported the ability of chitosan nanocapsules to enhance and prolong the oral absorption of peptides. In the present work, our goal was to design a new type of nanocapsules, using chitosan chemically modified with poly(ethylene glycol) (PEG) (0.5% and 1% pegylation degree) and to investigate the consequences of this modification on the in vitro and in vivo behaviour of the nanocapsules. Chitosan-PEG nanocapsules and the control PEG-coated nanoemulsions were obtained by the solvent displacement technique. Their size was in the range of 160-250 nm. Their zeta potential was greatly affected by the nature of the coating, being positive for chitosan-PEG nanocapsules and negative in the case of PEG-coated nanoemulsions. The presence of PEG, whether alone or grafted to chitosan, improved the stability of the nanocapsules in the gastrointestinal fluids. Using the Caco-2 model cell line it was observed that the pegylation of chitosan reduced the cytotoxicity of the nanocapsules. In addition, these nanocapsules did not cause a significant change in the transepithelial resistance of the monolayer. Finally, the results of the in vivo studies showed the capacity of chitosan-PEG nanocapsules to enhance and prolong the intestinal absorption of salmon calcitonin. Additionally, they indicated that the pegylation degree affected the in vivo performance of the nanocapsules. Therefore, by modulating the pegylation degree of chitosan, it was possible to obtain nanocapsules with a good stability, a low cytotoxicity and with absorption enhancing properties.
Rekha, M.R. & Sharma, C.P., 2009. Synthesis and evaluation of lauryl succinyl chitosan particles towards oral insulin delivery and absorption. Journal of controlled release : official journal of the Controlled Release Society, 135(2), pp.144-51. Available at: http://www.ncbi.nlm.nih.gov/pubmed/19331862 [Accessed March 15, 2012].
Abstract: In this work a novel chitosan derivative, lauryl succinyl chitosan (LSC) was developed for the purpose of evaluating its applications towards oral peptide delivery system. Nano/microparticles were developed from this derivative by sodium tripolyphosphate (TPP) cross linking. Human insulin was used as the model protein drug and the release kinetics was studied at gastrointestinal pH. The presence of succinyl carboxyl groups had inhibitory effect on the release kinetics of insulin at pH 1.2 minimizing up to about 8.5+/-0.45% in two hours. Results showed that the presence of hydrophobic moieties controlled the release of the loaded insulin from the particles at intestinal pH. The particles were negatively charged with size ranging from 315 nm to 1.090 microm. The mucoadhesive capacity was established ex vivo using the jejunum of rat intestine. Confocal microscopy studies proved the tight junction permeability in Caco 2 cells and in vivo uptake of the FITC-insulin from loaded nanoparticles by the rat intestinal epithelium. The results demonstrated that the modified chitosan with both hydrophilic (succinyl) and hydrophobic (lauryl) moieties had improved the release characteristics, mucoadhesivity as well as the permeability of the insulin compared to the native chitosan particles. The LSC2 particles were capable of reducing blood glucose levels in diabetic rats for the duration of about 6 h. This indicated that this novel derivative could be a promising candidate for oral peptide delivery.
Sakuma, S., Hayashi, M. & Akashi, M., 2001. Design of nanoparticles composed of graft copolymers for oral peptide delivery. Advanced drug delivery reviews, 47(1), pp.21-37. Available at: http://www.ncbi.nlm.nih.gov/pubmed/11251243 [Accessed April 8, 2012].
Abstract: The development of a dosage form that improves the absorption of peptide and protein drugs via the gastrointestinal tract is one of the greatest challenges in the pharmaceutical field. Many researchers have taken up the challenge, using approaches including mucoadhesive drug delivery, colon delivery, particulate drug delivery such as nanoparticles, microcapsules, liposomes, emulsions, micelles, and so on. The objective of this article is to provide the reader with outlines of novel nanoparticle technologies for oral peptide delivery based on polymer chemistry. The physicochemical properties of nanoparticles and their behavior on exposure to physiological media are greatly dominated by their chemical structures and surface characteristics. We will especially focus on the design of nanoparticles composed of novel graft copolymers having a hydrophobic backbone and hydrophilic branches as drug carriers.
Sasaki, Y. et al., 2011. Artificial chaperone polysaccharide nanogels for protein delivery: a thermodynamic study of protein-nanogel interactions using fluorescence correlation spectroscopy. Current drug discovery technologies, 8(4), pp.308-13. Available at: http://www.ncbi.nlm.nih.gov/pubmed/21711243 [Accessed April 8, 2012].
Abstract: Molecular chaperones selectively trap heat-denatured proteins or their intermediates, primarily by hydrophobic interactions, to prevent irreversible aggregation resulting from macromolecular host (molecular chaperone)-guest (protein) interactions. The molecular chaperone function is an important concept that is expected to lead to breakthroughs in drug delivery systems, especially for protein or peptide delivery in regenerative medicine, such as bone regeneration. We have reported that polysaccharide nanogels act as artificial molecular chaperones. To further clarify the molecular chaperone function of nanogels as protein carriers, the elucidation of nanogel-protein interactions are especially important. Here, we investigated the interaction of a protein with a polysaccharide nanogel using fluorescence correlation spectroscopy at variable temperatures, using fluorescence-labeled bovine serum albumin (BSA) as a model protein. In particular, thermodynamic parameters of the heat-induced complexation of protein with CHP nanogels were evaluated using the van’t Hoff plot. The plot shows that the CHP nanogels strongly complexed with heat-denatured BSA. The increased hydrophobicity of the denatured, unfolded protein may prefer complexation with amphiphilic hydrogel nanoparticles over complexation with the completely folded native protein. Thermodynamic parameters suggest that the complexation is entropically driven, rather than enthalpically, under the conditions studied.
Tan, M.L., Choong, P.F.M. & Dass, C.R., 2010. Recent developments in liposomes, microparticles and nanoparticles for protein and peptide drug delivery. Peptides, 31(1), pp.184-93. Available at: http://dx.doi.org/10.1016/j.peptides.2009.10.002 [Accessed March 2, 2012].
Abstract: Proteins and peptides are increasingly recognized as potential leads for the development of new therapeutics for a variety of human ailments. Due to their relatively specific mode of action, proteins and peptides can be administered at relatively low doses for therapeutic effects. As natural biological products, these low doses reduce the risk otherwise caused by other small molecular drugs or larger charged molecules. Unfortunately, their therapeutic potential and clinical application is frequently hampered by various obstacles to their successful delivery. This review discusses the recent developments in the fields of liposome, microparticle and nanoparticle pertinent to protein and peptide delivery covering those systems tested and/or validated in vivo.
Wang, G. & Uludag, H., 2008. Recent developments in nanoparticle-based drug delivery and targeting systems with emphasis on protein-based nanoparticles. Expert opinion on drug delivery, 5(5), pp.499-515. Available at: http://www.ncbi.nlm.nih.gov/pubmed/18491978 [Accessed April 8, 2012].
Abstract: Drug delivery systems with nm dimensions (nanoparticles [NPs]) are attracting increasing attention because they can sequester drugs in systemic circulation, prevent non-specific biodistribution, and target to specific tissues.
Yadav, S.C., Kumari, A. & Yadav, R., 2011. Development of peptide and protein nanotherapeutics by nanoencapsulation and nanobioconjugation. Peptides, 32(1), pp.173-87. Available at: http://www.ncbi.nlm.nih.gov/pubmed/20934475 [Accessed March 10, 2012].
Abstract: The targeted delivery of therapeutic peptide by nanocarriers systems requires the knowledge of interactions of nanomaterials with the biological environment, peptide release, and stability of therapeutic peptides. Therapeutic application of nanoencapsulated peptides are increasing exponentially and >1000 peptides in nanoencapsulated form are in different clinical/trial phase. This review covers current scenario of therapeutic protein and peptides encapsulation on polymer to metallic nanocarriers including methods of protein encapsulation, peptide bioconjugation on nanoparticles, stability enhancement of encapsulated proteins and its biomedical applications.