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William M Pardridge - One of the best experts on this subject based on the ideXlab platform.

  • Combined use of carboxyl-directed protein pegylation and vector-mediated blood-brain barrier Drug Delivery system optimizes brain uptake of brain-derived neurotrophic factor following intravenous administration.
    Pharmaceutical research, 1998
    Co-Authors: William M Pardridge, Toshiyasu Sakane
    Abstract:

    Purpose. Peptide Drug Delivery to the brain requires optimization of (a) plasma pharmacokinetics and (b) blood-brain barrier (BBB) permeability. In the present studies, plasma pharmacokinetics are improved with protein pegylation and BBB transport is facilitated with the use of vector-mediated Drug Delivery using the OX26 monoclonal antibody (MAb) to the rat transferrin receptor, which undergoes receptor-mediated transcytosis through the BBB in vivo.

  • Vector-mediated Delivery ofapolyamide ("Peptide") nucleic acid analogue throughtheblood-brain barrier invivo
    1995
    Co-Authors: William M Pardridge
    Abstract:

    Polyamide ("Peptide") nucleic acids (PNAs) aremolecules withantigene andantisense effects thatmay provetobeeffective neuropharmaceuticals ifthese molecules areenabled toundergo transport through thebrain capillary endothelial wall, whichmakesuptheblood-brain barrier in vivo. ThemodelPNAusedinthepresent studies isan18-mer thatisantisense totherevgeneofhumanimmunodeficiency virus type1andisbiotinylated attheaminoterminus and iodinated atatyrosine residue nearthecarboxyl terminus. Thebiotinylated PNAwaslinked toaconjugate ofstreptavidin (SA)andthe0X26murinemonoclonal antibody totherat transferrin receptor. Theblood-brain barrier isendowed with hightransferrin receptor concentrations, enabling the0X26- SAconjugate todeliver thebiotinylated PNA tothebrain. Although thebrainuptake ofthefreePNAwasnegligible following intravenous administration, thebrain uptake ofthe PNAwasincreased atleast 28-fold whenthePNAwasbound tothe0X26-SA vector. Thebrain uptake ofthePNAboundto the0X26-SAvector was0.1%oftheinjected dosepergramof brain at60minafter anintravenous injection, approximating thebrain uptake ofintravenously injected morphine. ThePNA boundtothe0X26-SAvector retained theability tobindto synthetic revmRNA asshownbyRNaseprotection assays. In summary, thepresent studies showthat while thetransport of PNAsacross theblood-brain barrier isnegligible, Delivery of these potential neuropharmaceutical Drugs tothebrain may beachieved bycoupling themtovector-mediated Peptide-Drug Delivery systems.

  • Vector-mediated Peptide Drug Delivery to the brain
    Advanced Drug Delivery Reviews, 1995
    Co-Authors: William M Pardridge
    Abstract:

    Abstract Peptides are potential new CNS pharmaceuticals should these highly water soluble compounds be made transportable through the brain capillary endothelial wall, which makes up the blood-brain barrier (BBB) in vivo. One strategy for Peptide Drug Delivery to the brain is the use of chimeric Peptides. The latter are formed when a transportable vector, such as cationized albumin or a receptor-specific monoclonal antibody, is conjugated to a therapeutic compound that is normally not transported through the BBB. The conjugation of Drugs to transport vectors is facilitated by the use of avidin-biotin technology. Existing transport vectors achieve degrees of brain Delivery that are approximately 40-fold greater than the brain Delivery of morphine, a neuroactive small molecule. Ongoing brain vector discovery programs may lead to new vectors with higher degrees of activity and brain specificity. The chimeric Peptide approach to brain Drug Delivery is an advanced technology that requires integrated progress in three inter-dependent spheres: the vector sphere, the linker sphere, and the Drug activity sphere. The complexities of the chimeric Peptide technology illustrate the importance of integrating CNS Drug discovery and CNS Drug Delivery as early as possible in the overall brain Drug development process.

  • transport of human recombinant brain derived neurotrophic factor bdnf through the rat blood brain barrier in vivo using vector mediated Peptide Drug Delivery
    Pharmaceutical Research, 1994
    Co-Authors: William M Pardridge, Youngsook Kang, Jody L Buciak
    Abstract:

    The blood–brain barrier (BBB) transport of brain-derived neurotrophic factor (BDNF) in anesthetized rats was examined in the present studies using vector-mediated Peptide Drug Delivery. Following tritiation, the BDNF was biotinylated via a disulfide linker and was coupled to a covalent conjugate of neutral avidin (NLA), which binds the biotinylated Peptide with a high affinity, and the murine OX26 monoclonal antibody to the rat transferrin receptor. Owing to the abundance of transferrin receptors on brain capillary endothelium, the OX26 monoclonal antibody undergoes receptor-mediated transcytosis through the BBB, and the NLA–OX26 conjugate transports biotinylated Peptide therapeutics through the BBB. The present studies show that while unconjugated BDNF was not transported through the BBB in vivo, the conjugation of biotinylated BDNF to the NLA–OX26 vector resulted in a marked increase in the brain Delivery of BDNF, as defined by measurements of the percentage of the injected dose (ID) delivered per gram of brain. Although BDNF was not transported through the BBB in vivo, this cationic Peptide was avidly bound by isolated human brain capillaries via a low-affinity, high-capacity system that was inhibited by protamine and by serum protein binding of BDNF. In conclusion, these studies show that the Delivery of unconjugated BDNF to brain is nil owing to the combined effects of negligible BBB transport and rapid systemic clearance of intravenous administered BDNF. The brain Delivery of BDNF may be augmented by conjugation of BDNF to BBB Drug Delivery vectors, such as the NLA–OX26 conjugate.

  • Transport of Human Recombinant Brain-Derived Neurotrophic Factor (BDNF) Through the Rat Blood−Brain Barrier in Vivo Using Vector-Mediated Peptide Drug Delivery
    Pharmaceutical Research, 1994
    Co-Authors: William M Pardridge, Youngsook Kang, Jody L Buciak
    Abstract:

    The blood–brain barrier (BBB) transport of brain-derived neurotrophic factor (BDNF) in anesthetized rats was examined in the present studies using vector-mediated Peptide Drug Delivery. Following tritiation, the BDNF was biotinylated via a disulfide linker and was coupled to a covalent conjugate of neutral avidin (NLA), which binds the biotinylated Peptide with a high affinity, and the murine OX26 monoclonal antibody to the rat transferrin receptor. Owing to the abundance of transferrin receptors on brain capillary endothelium, the OX26 monoclonal antibody undergoes receptor-mediated transcytosis through the BBB, and the NLA–OX26 conjugate transports biotinylated Peptide therapeutics through the BBB. The present studies show that while unconjugated BDNF was not transported through the BBB in vivo , the conjugation of biotinylated BDNF to the NLA–OX26 vector resulted in a marked increase in the brain Delivery of BDNF, as defined by measurements of the percentage of the injected dose (ID) delivered per gram of brain. Although BDNF was not transported through the BBB in vivo , this cationic Peptide was avidly bound by isolated human brain capillaries via a low-affinity, high-capacity system that was inhibited by protamine and by serum protein binding of BDNF. In conclusion, these studies show that the Delivery of unconjugated BDNF to brain is nil owing to the combined effects of negligible BBB transport and rapid systemic clearance of intravenous administered BDNF. The brain Delivery of BDNF may be augmented by conjugation of BDNF to BBB Drug Delivery vectors, such as the NLA–OX26 conjugate.

Andreas Bernkop-schnürch - One of the best experts on this subject based on the ideXlab platform.

  • Comparison of the protective effect of self-emulsifying Peptide Drug Delivery systems towards intestinal proteases and glutathione.
    International journal of pharmaceutics, 2017
    Co-Authors: Gergely Hetenyi, Janine Griesser, Frederic Demarne, Vincent Jannin, Michael Moser, Andreas Bernkop-schnürch
    Abstract:

    Abstract Aim The aim of this study was to evaluate the protective effect of self-emulsifying Drug Delivery systems (SEDDS) for therapeutic Peptides towards intestinal proteases and reduced glutathione (GSH). Methods Sodium docusate was applied as anionic surfactant for hydrophobic ion pairing with leuprorelin (LEU), insulin (INS) and desmopressin (DES). The complexes were loaded into SEDDS that were characterized regarding droplet size distribution and zeta potential. The release profile of the Peptides was examined by dialysis membrane method. Enzymatic digestion studies were performed by applying α-chymotrypsin, trypsin and elastase. Furthermore, the protective effect of SEDDS towards degradation through thiol-disulfide exchange reactions was examined by addition of GSH. Results SEDDS showed a mean droplet size of 0.27–3.9 μm and a zeta potential of –25 to –33 mV. All formulations provided a sustained release of the Peptides over 6 h. Degradation of the model Peptides by intestinal proteases and GSH could only be observed in the release medium. In the oily phase of SEDDS neither any of the proteases nor GSH was soluble (≤0.1%). Furthermore, no degradation of the model Peptides by proteases and GSH took place in the oily phase of SEDDS. Conclusion SEDDS can provide a 100% protective effect towards protease degradation and deactivation by GSH. According to this, SEDDS might be promising tools for oral Delivery of Peptide Drugs.

  • Hydrophobic ion pairing: Key to highly payloaded self-emulsifying Peptide Drug Delivery systems.
    International journal of pharmaceutics, 2017
    Co-Authors: Janine Griesser, Gergely Hetenyi, Frederic Demarne, Vincent Jannin, Michael Moser, Andreas Bernkop-schnürch
    Abstract:

    The aim of this study was the formation and characterization of various ion pairs of therapeutic Peptides with different surfactants in order to reach a high payload in self-emulsifying Drug delivering systems (SEDDS). Hydrophobic ion pairs (HIP) were formed between the anionic surfactants sodium docusate, dodecylsulfate and oleate and the Peptides leuprorelin (LEU), insulin (INS) and desmopressin (DES). The efficiency of HIP formation was evaluated by quantifying the amount of formed complexes, log P value determination in n-octanol/water via HPLC and zeta potential measurements. Solvents and surfactants were screened regarding their complex solubilizing properties. Subsequently, Peptide complexes were incorporated into SEDDS followed by payload and stability determination. Independent from the type of Peptide, docusate showed the most efficient HIP properties followed by dodecylsulfate and oleate. Ratios of 2:1 for LEU, 6:1 for INS and 1.5:1 for DES led to the highest quantity of formed complexes with docusate and log P increased at least by 3 units. The more docusate was added to each Peptide, the more negative became the zeta potential of the resulting complex. Incorporating these optimized complexes into novel SEDDS containing Capryol 90, Labrafil M 2125 CS, Labrasol ALF, Peceol, propylene glycol, tetraglycol, Transcutol HP and Tween 20 allowed payloads of the LEU, DES and INS complexes above 10%. Moreover, SEDDS exhibited high stability and constant negative zeta potential over a 4h incubation time. Following the procedure described herein payloads >10% can be achieved for Peptide Drugs in SEDDS. Copyright © 2017 Elsevier B.V. All rights reserved.

  • Evaluation of Peptide Drug Delivery via skin barrier-impact of permeation enhancers
    Journal of Drug Delivery Science and Technology, 2017
    Co-Authors: Flavia Laffleur, Andreas Bernkop-schnürch
    Abstract:

    Abstract Background/purpose Non-invasive topical Delivery of Peptides and proteins will emerge the pharmaceutical research by circumventing the disadvantages along with invasive route. Therefore it was aimed to investigate the impact of permeation enhancers ionic as well as non-ionic on Peptide permeation through porcine abdominal skin. Methods TriPeptide Leu-Gly-Gly was evaluated for is toxicity profile along with Caco-2 cells. Furthermore Leu-Gly-Gly was fluorescence labelled with Fluorescein-isothiocyanate. For permeation studies, porcine abdominal skin was mounted on Franz-diffusion cells and investigated due to the addition of 0.5% (w/w) anionic and non-ionic surfactants in comparison to triPeptide alone. Results The safety profile of triPeptide show no toxicity at all according to Resazurin assay. Pre-studies with sodium fluorescein set the parameter for Peptide permeation studies. TriPeptide was successfully labelled with FITC determined by TNBS assay. Tween20 revealed the most promising results for permeation enhancing potential with a P app of 2.78 × 10 −6  cm/s. Conclusion Taking these findings in consideration, ionic surfactants are safe to use and exhibit the most beneficial permeation enhancing effect in Peptide Delivery via skin.

  • Self-emulsifying Drug Delivery systems in oral (poly)Peptide Drug Delivery
    Expert opinion on drug delivery, 2015
    Co-Authors: Gintare Leonaviciute, Andreas Bernkop-schnürch
    Abstract:

    Introduction: Oral administration of most therapeutic Peptides and proteins is mainly restricted due to the enzymatic and absorption membrane barrier of the GI tract. In order to overcome these barriers, various technologies have been explored. Among them, self-emulsifying Drug Delivery systems (SEDDS) received considerable attention as potential carriers to facilitate oral Peptide and protein Delivery in recent years.Areas covered: This review article intends to summarize physiological barriers which limit the bioavailability of orally administrated Peptide and protein Drugs. Furthermore, the potential of SEDDS to protect incorporated Peptides and proteins towards peptidases and proteases and to penetrate the mucus layer is reviewed. Their permeation-enhancing properties and their ability to release the Drug in a controlled way are described. Moreover, this review covers the results of in vivo studies providing evidence for this promising approach.Expert opinion: As SEDDS can: i) provide a protective eff...

  • Development and in vivo characterization of a novel Peptide Drug Delivery system providing extended plasma half life.
    Journal of controlled release : official journal of the Controlled Release Society, 2011
    Co-Authors: Gul Shahnaz, Glen Perera, Flavia Laffleur, Javed Iqbal, Deni Rahmat, Denise Rossi, Andreas Bernkop-schnürch
    Abstract:

    Abstract It was the aim of this study to develop a sustained parenteral Peptide (DALCE) Delivery system by the immobilization of DALCE to thiolated carboxymethyl dextran-cysteine (CMD-Cys) via disulfide bond formation. The resulting CMD-Cys–DALCE conjugate displayed a 22.6 ± 7.9% (m/m) of DALCE (mean ± S.D.; n  = 3). The conjugation of DALCE with CMD-Cys was confirmed by FTIR-ATR spectroscopy. In vitro release studies of conjugate CMD-Cys–DALCE in the presence of 2 μM/ml reduced glutathione (GSH) being also available in the plasma showed a sustained Peptide release over a time period of 8 h, because of thiol/disulfide exchange reactions. For in vivo pharmacokinetic study, DALCE and CMD-Cys–DALCE were administered intravenously to male Sprague–Dawley rats at a dose of 1 mg/kg. The AUC 0-8 (ng.min/ml) was determined to be 268848 ± 924 and 40019 ± 495 for CMD-Cys–DALCE and DALCE, respectively. The mean residence time (MRT) was determined to be 256 ± 8 and 53.1 ± 9.5 min for CMD-Cys–DALCE and for DALCE, respectively. CMD-Cys–DALCE showed a more than 5-fold increased elimination half-life ( p p p

Nuo Wang - One of the best experts on this subject based on the ideXlab platform.

  • poly vinyl alcohol nanoparticles prepared by freezing thawing process for protein Peptide Drug Delivery
    Journal of Controlled Release, 1998
    Co-Authors: Nuo Wang
    Abstract:

    Abstract Poly(vinyl alcohol) (PVA) hydrogel nanoparticles have been prepared by using a water-in-oil emulsion technology plus cyclic freezing–thawing process. The PVA hydrogel nanoparticles prepared by this method are suitable for protein/Peptide Drug Delivery since formation of the hydrogel does not require crosslinking agents or other adjuvants and does not involve any residual monomer. Particularly, there is no emulsifier involved in this new method. Bovine serum albumin (BSA), as a model protein Drug, is incorporated into the PVA hydrogel nanoparticles. The PVA hydrogel nanoparticles possess a skewed or log-normal size distribution. The average diameter of the PVA hydrogel nanoparticles is 675.5±42.7 nm. Protein Drug loading efficiency in the PVA hydrogel nanoparticles is 96.2±3.8%. The PVA hydrogel nanoparticles swell in an aqueous solution and the swelling degree increases with the increase of temperature. In vitro release studies show that the BSA release from the nanoparticles can be prolonged to 30 h. The BSA release follows a diffusion-controlled mechanism. The number of freezing–thawing cycle and release temperature both influence BSA release rate considerably. Less freezing–thawing cycle or higher release temperature leads to faster Drug release. The BSA is stable during preparation of the PVA hydrogel nanoparticles.

  • Poly(vinyl alcohol) nanoparticles prepared by freezing-thawing process for protein/Peptide Drug Delivery.
    Journal of controlled release : official journal of the Controlled Release Society, 1998
    Co-Authors: Nuo Wang
    Abstract:

    Poly(vinyl alcohol) (PVA) hydrogel nanoparticles have been prepared by using a water-in-oil emulsion technology plus cyclic freezing-thawing process. The PVA hydrogel nanoparticles prepared by this method are suitable for protein/Peptide Drug Delivery since formation of the hydrogel does not require crosslinking agents or other adjuvants and does not involve any residual monomer. Particularly, there is no emulsifier involved in this new method. Bovine serum albumin (BSA), as a model protein Drug, is incorporated into the PVA hydrogel nanoparticles. The PVA hydrogel nanoparticles possess a skewed or log-normal size distribution. The average diameter of the PVA hydrogel nanoparticles is 675.5+/-42.7 nm. Protein Drug loading efficiency in the PVA hydrogel nanoparticles is 96.2+/-3.8%. The PVA hydrogel nanoparticles swell in an aqueous solution and the swelling degree increases with the increase of temperature. In vitro release studies show that the BSA release from the nanoparticles can be prolonged to 30 h. The BSA release follows a diffusion-controlled mechanism. The number of freezing-thawing cycle and release temperature both influence BSA release rate considerably. Less freezing-thawing cycle or higher release temperature leads to faster Drug release. The BSA is stable during preparation of the PVA hydrogel nanoparticles.

  • Poly(vinyl alcohol) nanoparticles prepared by freezing–thawing process for protein/Peptide Drug Delivery
    Journal of Controlled Release, 1998
    Co-Authors: Nuo Wang
    Abstract:

    Poly(vinyl alcohol) (PVA) hydrogel nanoparticles have been prepared by using a water-in-oil emulsion technology plus cyclic freezing-thawing process. The PVA hydrogel nanoparticles prepared by this method are suitable for protein/Peptide Drug Delivery since formation of the hydrogel does not require crosslinking agents or other adjuvants and does not involve any residual monomer. Particularly, there is no emulsifier involved in this new method. Bovine serum albumin (BSA), as a model protein Drug, is incorporated into the PVA hydrogel nanoparticles. The PVA hydrogel nanoparticles possess a skewed or log-normal size distribution. The average diameter of the PVA hydrogel nanoparticles is 675.5+/-42.7 nm. Protein Drug loading efficiency in the PVA hydrogel nanoparticles is 96.2+/-3.8%. The PVA hydrogel nanoparticles swell in an aqueous solution and the swelling degree increases with the increase of temperature. In vitro release studies show that the BSA release from the nanoparticles can be prolonged to 30 h. The BSA release follows a diffusion-controlled mechanism. The number of freezing-thawing cycle and release temperature both influence BSA release rate considerably. Less freezing-thawing cycle or higher release temperature leads to faster Drug release. The BSA is stable during preparation of the PVA hydrogel nanoparticles.

  • Preparation and Characterization of Agarose Hydrogel Nanoparticles for Protein and Peptide Drug Delivery
    Pharmaceutical development and technology, 1997
    Co-Authors: Nuo Wang
    Abstract:

    The purpose of this work was to develop and characterize a protein and Peptide injectable Drug Delivery system in agarose hydrogel nanoparticles. The nanoparticles were prepared by using a new emulsion-converted-to-suspension in situ method. This is an emulsifier-free method that has advantages for protein and Peptide Drug encapsulations. Ovalbumin, used as a model protein Drug, was successfully encapsulated into nearly spherical agarose hydrogel nanoparticles under mild conditions. The nanoparticles possessed a log-normal size distribution with an average size of 504 nm. They imbibed a large amount of water (66.85% to 84.33%) and the water content was a function of temperature; the water content increased with increase in temperature. Release studies of the ovalbumin from the agarose hydrogel nanoparticles revealed a diffusion-controlled release mechanism with a temperature dependence; the ovalbumin release rate was higher at 37 degrees C than that at room temperature. The great biocompatibility of agarose hydrogel, plus the mild conditions for Drug encapsulation, make the agarose hydrogel nanoparticles a potential system for protein and Peptide Drug Delivery.

  • A novel biodegradable system based on gelatin nanoparticles and poly(lactic-co-glycolic acid) microspheres for protein and Peptide Drug Delivery
    Journal of pharmaceutical sciences, 1997
    Co-Authors: Nuo Wang
    Abstract:

    Gelatin nanoparticle-poly(lactic-co-glycolic acid) (PLGA) microsphere composites were prepared by encapsulating protein-loaded gelatin nanoparticles in PLGA microspheres. This encapsulation was conducted by using a phase separation method and a solvent extraction method. The average diameter of the gelatin nanoparticle-PLGA microsphere composites is between 160 and 175 μm. Protein loading efficiency is 93.2% for the nanoparticle-microsphere composite prepared by the phase separation method, while it is 31.31% for the composite prepared by the solvent extraction method. Protein release experiments indicate that this new composite system possesses sustained release characteristics. This system also demonstrates the capability of preventing the denaturation of protein Drugs.

Tamara Minko - One of the best experts on this subject based on the ideXlab platform.

  • Multifunctional Tumor-Targeted Polymer-Peptide-Drug Delivery System for Treatment of Primary and Metastatic Cancers
    Pharmaceutical Research, 2010
    Co-Authors: Pooja Chandna, Jayant J. Khandare, Lorna Rodriguez-rodriguez, Tamara Minko
    Abstract:

    Purpose In order to improve Drug Delivery to Drug-resistant ovarian tumors, we constructed a multifunctional polymer-Peptide-Drug conjugate (PPDC) system for effective treatment of primary and metastatic ovarian cancers. Methods The PPDC consists of the poly(Ethylene Glycol) (PEG) polymeric carrier conjugated via citric acid spacers to anticancer Drug (Camptothecin, CPT), tumor targeting moiety (LRHR, a synthetic analog of luteinizing hormone-releasing hormone) and a suppressor of cellular antiapoptotic defense (BH3 Peptide). To test the conjugates in vitro and in vivo , cancer cells were isolated from tissue samples obtained from patients with ovarian primary tumor and metastatic malignant ascites. Results It was found that cells isolated from malignant ascites were more aggressive in terms of tumor growth and more resistant to chemotherapy when compared with those isolated from primary tumors. PPDC containing two copies of Drugs and Peptides was most efficient in treatment of primary tumors and intraperitoneal metastases. Multiple treatments with this PPDC led to almost complete regression of primary tumor and prevented growth of malignant ascites. Conclusion The proposed multifunctional polymeric Delivery system which consists of multiple copies of the Drug and Peptides demonstrated significantly higher antitumor activity in primary and metastatic cancers when compared with Drug alone and PEG-CPT conjugate.

  • Multifunctional tumor-targeted polymer-Peptide-Drug Delivery system for treatment of primary and metastatic cancers.
    Pharmaceutical research, 2010
    Co-Authors: Pooja Chandna, Jayant J. Khandare, Lorna Rodriguez-rodriguez, Elizabeth Ber, Tamara Minko
    Abstract:

    Purpose In order to improve Drug Delivery to Drug-resistant ovarian tumors, we constructed a multifunctional polymer-Peptide-Drug conjugate (PPDC) system for effective treatment of primary and metastatic ovarian cancers.

Peter X - One of the best experts on this subject based on the ideXlab platform.

  • A lanthanide-Peptide-derived bacterium-like nanotheranostic with high tumor-targeting, -imaging and -killing properties.
    Biomaterials, 2019
    Co-Authors: Jin Yan, Lijuan Wang, Bo Lei, Peng Hou, Peter X
    Abstract:

    Abstract Nanostructures formed with bioactive Peptides offer an exciting prospect in clinical oncology as a novel class of therapeutic agents for human cancers. Despite their therapeutic potential, however, Peptide-based nanomedicines are often inefficacious in vivo due to low cargo-loading efficiency, poor tumor cell-targeting specificity and limited Drug accumulation in tumor tissues. Here, we describe the design, via assembly of a p53-activating Peptide termed PMI, functionalized PEG and fluorescent lanthanide oxyfluoride nanocrystals , of a novel nanotheranostic shaped in flexible rods. This lanthanide-Peptide nanorod or LProd of bionic nature exhibited significantly enhanced tumor-targeting and -imaging properties compared to its spherical counterpart. Importantly, LProd potently inhibited tumor growth in a mouse model of human colon cancer through activating tumor suppressor protein p53 via MDM2/MDMX antagonism, while maintaining a highly favorable biosafety profile. Our data demonstrate that LProd as a multifunctional theranostic platform is ideally suited for tumor-specific Peptide Drug Delivery with real-time disease tracking, thereby broadly impacting clinical development of antitumor Peptides.

  • self assembled Peptide lanthanide nanoclusters for safe tumor therapy overcoming and utilizing biological barriers to Peptide Drug Delivery
    ACS Nano, 2018
    Co-Authors: Wangxiao He, Yongping Shao, Guang Yang, Wuyuan Lu, Yaping Du, Peter X
    Abstract:

    Developing a sophisticated nanomedicine platform to deliver therapeutics effectively and safely into tumor/cancer cells remains challenging in the field of nanomedicine. In particular, reliable Peptide Drug Delivery systems capable of overcoming biological barriers are still lacking. Here, we developed a simple, rapid, and robust strategy to manufacture nanoclusters of ∼90 nm in diameter that are self-assembled from lanthanide-doped nanoparticles (5 nm), two anticancer Peptides with different targets (BIM and PMI), and one cyclic Peptide iNGR targeted to cancer cells. The Peptide–lanthanide nanoclusters (LDC-PMI-BIM-iNGR) enhanced the resistance of Peptide Drugs to proteolysis, disassembled in response to reductive conditions that are present in the tumor microenvironment and inhibited cancer cell growth in vitro and in vivo. Notably, LDC-PMI-BIM-iNGR exhibited extremely low systemic toxicity and side effects in vivo. Thus, the Peptide–lanthanide nanocluster may serve as an ideal multifunctional platform ...