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Liposome antibodies

Susan Hua
Targeted delivery of therapeutics to the uterus is an important goal in the treatment of obstetric complications, such as preterm labor, postpartum hemorrhage and dysfunctional labor. Current treatment for these obstetric complications is challenging, as there are limited effective and safe therapeutic options available. We have developed a targeted drug delivery system for the uterus by conjugating anti-oxytocin receptor (OTR) antibodies to the surface of PEGylated liposomes (OTR-PEG-ILs). The functionality of the OTR-PEG-ILs have previously been evaluated on human and murine myometrial tissues as well as in vivo in a murine model of preterm labor...
December 10, 2018: Journal of Liposome Research
Jun Shi, Yanting Wu, Siyi Guo, Huidi Zhang, Guitian Chen, Xiaoqi Xu
The aim of this study was to investigate the efficacy of anti-VEGF antibody-modified Paeonol liposome gels (PAE-BEV-lip gels) in the prevention and treatment of Hypertrophic Scars (HSs). Systematic optimization of the encapsulation process of anti-VEGF antibody-modified Paeonol liposomes (PAE-BEV-lips) was performed using Box-Behnken design with the optimized parameters as follows: SPC concentration of 7.36 mg·mL-1 ; SPC-Chol-PAE:pNP-PEG3000 -DOPE:BVE-PEG3000 -DOPE ratio of 14:5:4:0.28:0.05, w/w; the hydration temperature of 41 °C; stripping using pH 7...
December 4, 2018: Drug Development and Industrial Pharmacy
Sidhartha Chaudhury, Elizabeth H Duncan, Tanmaya Atre, Casey K Storme, Kevin Beck, Stephen A Kaba, David E Lanar, Elke S Bergmann-Leitner
Adjuvants have long been critical components of vaccines, but the exact mechanisms of their action and precisely how they alter or enhance vaccine-induced immune responses are often unclear. In this study, we used broad immunoprofiling of antibody, cellular, and cytokine responses, combined with data integration and machine learning to gain insight into the impact of different adjuvant formulations on vaccine-induced immune responses. A Self-Assembling Protein Nanoparticles (SAPN) presenting the malarial circumsporozoite protein (CSP) was used as a model vaccine, adjuvanted with three different liposomal formulations: liposome plus Alum (ALFA), liposome plus QS21 (ALFQ), and both (ALFQA)...
November 30, 2018: Scientific Reports
Anna Wrona
PURPOSE OF REVIEW: Despite aggressive treatment based on definitive chemoradiotherapy, 5-year overall survival in unresectable stage III nonsmall cell lung cancer remains poor (15-20%). The novel immunotherapy based on immune checkpoint inhibitors (ICIs) presents as the therapeutic 'Holly Grail' in lung cancer treatment. RECENT FINDINGS: Preclinical models provide evidence of immunotherapy-radiotherapy (IM-RT) synergy. The exposure to ionizing radiation turns tumor in an in-situ vaccine, primes the innate immune system, increases immunotherapy efficacy by overcoming the immunosuppressive microenvironment of immune-resistant tumors and promotes a systemic, out-of-field antitumor T-cell-mediated response called abscopal effect...
January 2019: Current Opinion in Oncology
Jianqin Lu, Xiangsheng Liu, Yu-Pei Liao, Xiang Wang, Ayman Ahmed, Wen Jiang, Ying Ji, Huan Meng, Andre E Nel
Immunotherapy provides the best approach to reduce the high mortality of metastatic breast cancer (BC). We demonstrate a chemo-immunotherapy approach, which utilizes a liposomal carrier to simultaneously trigger immunogenic cell death (ICD) as well as interfere in the regionally overexpressed immunosuppressive effect of indoleamine 2,3-dioxygenase (IDO-1) at the BC tumor site. The liposome was constructed by self-assembly of a phospholipid-conjugated prodrug, indoximod (IND), which inhibits the IDO-1 pathway, followed by the remote loading of the ICD-inducing chemo drug, doxorubicin (DOX)...
November 27, 2018: ACS Nano
Chengjie Lin, Zhigao Hu, Guandou Yuan, Huizhao Su, Yonglian Zeng, Zhenya Guo, Fudi Zhong, Keqing Jiang, He Songqing
Pancreatic cancer is one of the deadliest cancers across the world with an average 5-year survival rate of less than <6%. In this study, gemcitabine (GEM) and HIF1α-siRNA loaded GE-11 peptide conjugated liposome was successfully prepared and evaluated for its antitumor efficacy in pancreatic cancer cells. The GE11 increased the targeting specificity of liposome carrier and increased the intracellular concentrations in the cancer cells. Furthermore, synergistic combination of GEM and HIF1a-siRNA exhibited remarkable improvement in the declining of cancer cell proliferations...
November 27, 2018: Journal of Drug Targeting
Pal Patel, Nikita Meghani, Krupa Kansara, Ashutosh Kumar
Nanotechnology is gaining significant attention worldwide for the treatment of complex disease such as AIDS (acquired immune deficiency syndrome), cancer and rheumatoid arthritis. Nanomedicine is the application of nanotechnology used for diagnosis and treatment for the disease that includes the preservation and improvement of human health by covering an area such as drug delivery using nanocarriers, nanotheranostics and nanovaccinology. The present article provides an insight on several aspects of nanomedicine such as usages of multiple type of nanocarriers, their status, advantages and disadvantages with reference to cancer and rheumatoid arthritis...
November 26, 2018: Current Drug Metabolism
Steffen Wöll, Christopher Bachran, Stefan Schiller, Matthias Schröder, Lena Conrad, Regina Scherließ, Lee Kim Swee
The therapeutic index of drugs can be increased via drug encapsulation in actively targeted, meaning ligand modified drug delivery systems. The manufacturing of such targeted drug delivery systems, in particular the conjugation between drug carrier and ligand, can be done by enzymatic conjugation methods, exploiting the site-specific, bioorthogonal nature of these reactions. The use of such enzymes like Sortase-A transpeptidase requires efficient purification methods, as residuals of the enzyme may be responsible for immunogenic potential and drug product instabilities...
November 20, 2018: European Journal of Pharmaceutics and Biopharmaceutics
Jacob M Rowe
The FLT3 inhibitor midostaurin, the antibody-drug conjugate gemtuzumab ozogamicin, CPX-351 (liposomal daunorubicin and cytarabine), and the IDH2 inhibitor enasidenib are among the novel agents approved for use in the clinic this past year. This year, 2018, already has seen the regulatory approval of the BCL2 inhibitor venetoclax in the form of breakthrough designation and the IDH1 inhibitor ivosidenib received full FDA approval. Much remains to be learned about how best to use these drugs to improve patient outcomes and how best to employ and interpret next-generation sequencing to determine measurable residual disease (MRD) levels that can more accurately predict risk of relapse...
December 2018: Best Practice & Research. Clinical Haematology
Federico Leonel Parra, Ayelen Tatiana Caimi, Maria Julia Altube, Diego Esteban Cargnelutti, Mónica Elba Vermeulen, Marcelo Alexandre de Farias, Rodrigo Villares Portugal, Maria Jose Morilla, Eder Lilia Romero
Hyperhalophilic archaebacteria exclusively produce sn2,3 diphytanylglycerol diether archaeolipids, unique structures absent in bacteria and eukaryotes. Nanovesicles made of archaeolipids known as nanoarchaeosomes (nanoARC), possess highly stable bilayers, some of them displaying specific targeting ability. Here we hypothesize that nanoARC made from Halorubrum tebenquichense archaebacteria, may constitute efficient carriers for the TLR7 agonist imiquimod (IMQ). NanoARC-IMQ takes advantage of the intense interaction between IMQ and the highly disordered, poorly fluid branched archaeolipid bilayers, rich in archaeol analog of methyl ester of phosphatidylglycerophosphate (PGP-Me), a natural ligand of scavenger receptor A1 (SR-A1)...
2018: Frontiers in Bioengineering and Biotechnology
Santosh Dhakal, Xingguo Cheng, John Salcido, Sankar Renu, Kathy Bondra, Yashavantha Shaan Lakshmanappa, Christina Misch, Shristi Ghimire, Ninoshkaly Feliciano-Ruiz, Bradley Hogshead, Steven Krakowka, Kenneth Carson, Joseph McDonough, Chang Won Lee, Gourapura J Renukaradhya
Background: Influenza (flu) is a constant threat to humans and animals, and vaccination is one of the most effective ways to mitigate the disease. Due to incomplete protection induced by current flu vaccines, development of novel flu vaccine candidates is warranted to achieve greater efficacy against constantly evolving flu viruses. Methods: In the present study, we used liposome nanoparticle (<200 nm diameter)-based subunit flu vaccine containing ten encapsulated highly conserved B and T cell epitope peptides to induce protective immune response against a zoonotic swine influenza A virus (SwIAV) H1N1 challenge infection in a pig model...
2018: International Journal of Nanomedicine
Mario Luppi, Francesco Fabbiano, Giuseppe Visani, Giovanni Martinelli, Adriano Venditti
Acute myeloid leukemia (AML) is a complex hematological disease characterized by genetic and clinical heterogeneity. Recent advances in the understanding of AML pathogenesis have paved the way for the development of new agents targeting specific molecules or mechanisms that contribute to finally move beyond the current standard of care, which is "3 + 7" regimen. In particular, new therapeutic options such as targeted therapies (midostaurin and enasidenib), monoclonal antibodies (gemtuzumab ozogamicin), and a novel liposomal formulation of cytarabine and daunorubicin (CPX-351) have been recently approved, and will be soon available for the treatment of adult patients with AML...
November 9, 2018: Cancers
Kyle J Bednar, Lakeya Hardy, Johanna Smeekens, Dharmendra Raghuwanshi, Shiteng Duan, Mike D Kulis, Matthew S Macauley
Antibody responses provide critical protective immunity to a wide array of pathogens. There remains a high interest in generating robust antibodies for vaccination as well as understand how pathogenic antibody responses develop in allergies and autoimmune disease. Generating robust antigen-specific antibody responses is not always trivial. In mouse models, it often requires multiple rounds of immunizations with adjuvant that leads to a great deal of variability in the levels of induced antibodies. One example is in mouse models of peanut allergies where more robust and reproducible models that minimize mouse numbers and the use of adjuvant would be beneficial...
October 25, 2018: Journal of Visualized Experiments: JoVE
Talar Tokatlian, Daniel W Kulp, Andrew A Mutafyan, Christopher A Jones, Sergey Menis, Erik Georgeson, Mike Kubitz, Michael H Zhang, Mariane B Melo, Murillo Silva, Dong Soo Yun, William R Schief, Darrell J Irvine
An HIV vaccine capable of eliciting durable neutralizing antibody responses continues to be an important unmet need. Multivalent nanoparticles displaying a high density of envelope trimers may be promising immunogen forms to elicit strong and durable humoral responses to HIV, but critical particle design criteria remain to be fully defined. To this end, we developed strategies to covalently anchor a stabilized gp140 trimer, BG505 MD39, on the surfaces of synthetic liposomes to study the effects of trimer density and vesicle stability on vaccine-elicited humoral responses in mice...
November 8, 2018: Scientific Reports
Tatiana A Slastnikova, A V Ulasov, A A Rosenkranz, A S Sobolev
A dominant area of antibody research is the extension of the use of this mighty experimental and therapeutic tool for the specific detection of molecules for diagnostics, visualization, and activity blocking. Despite the ability to raise antibodies against different proteins, numerous applications of antibodies in basic research fields, clinical practice, and biotechnology are restricted to permeabilized cells or extracellular antigens, such as membrane or secreted proteins. With the exception of small groups of autoantibodies, natural antibodies to intracellular targets cannot be used within living cells...
2018: Frontiers in Pharmacology
Kuan-Chieh Liu, Arundhathi Arivajiagane, Shang-Jung Wu, Shey-Cherng Tzou, Chiao-Yun Chen, Yun-Ming Wang
A novel EGFR-targeting, thermal-sensitive multifunctional liposome (TSML) was developed based on manganese-dopedmagnetism-engineered iron oxide nanoparticles (MnMEIOs) and gold nanorods (AuNRs) for efficient photothermal therapy and magnetic resonance (MR) imaging. An Erbitux-conjugatedTSML (Erb-TSML) was encapsulated with doxorubicin and gold nanorods conjugated with manganese-dopedmagnetism-engineered iron oxide nanoparticles, for theranostic applications of EGFR-positive tumors. The Erb-TSML selectively targeted EGFR-positive tumors and promoted tumor destruction by laser activation...
November 1, 2018: Nanomedicine: Nanotechnology, Biology, and Medicine
Zenon Pawlak, Aleksandra Mrela, Mariusz Kaczmarek, Mieczyslaw Cieszko, Wieslaw Urbaniak
Lipid profiles of injured and healthy knees' synovial fluids show significant differences. The paper shows that osteoporosis changes the SF content and the lipid profile substantially. It is observed an increase in phospholipids over the fractured ones, and in the lysophosphatidylcholine levels because of the probable release of phospholipases from osteoporosis tissues. To estimate the implication of the lipid environment in case the AC changes, we measured friction coefficient normal samples, e-OA, and l-OA...
October 30, 2018: Bio Systems
Lucyna Matusewicz, Joanna Podkalicka, Aleksander F Sikorski
Lipophilic statins are promising candidates for breast cancer treatment. However, anticancer therapy requires much higher doses of statins than can be delivered orally, and such high doses are known to exert more adverse effects. The main objective of our study was to design a targeted, therapeutic liposomal carrier of simvastatin characterised by high stability and specificity towards breast cancer cells. We chose SKBR3, the cell line that showed the highest sensitivity for simvastatin and liposomal simvastatin treatment...
November 1, 2018: Cancers
Gayong Shim, Dongyoon Kim, Sangbin Lee, Rae Sung Chang, Junho Byun, Yu-Kyoung Oh
We designed a bacterio-mimetic nanoparticle that can noncovalently control the orientation of attached antibodies. Liposomes with Fc-binding peptide (FcBP), formulated using FcBP-conjugated PEGylated lipid, were used as model nanoparticles. Compared with control nanoparticles surface-modified with antibody covalently attached via maleimide functional groups (Mal-NPs), FcBP-capped nanoparticles (FcBP-NPs) exhibited greater binding affinity to the target protein. Human epidermal growth factor receptor 2 (HER2)-specific antibody-modified FcBP-NPs (HER2/FcBP-NPs) showed 5...
October 24, 2018: Nanomedicine: Nanotechnology, Biology, and Medicine
Pamela Munster, Ian E Krop, Patricia LoRusso, Cynthia Ma, Barry A Siegel, Anthony F Shields, István Molnár, Thomas J Wickham, Joseph Reynolds, Karen Campbell, Bart S Hendriks, Bambang S Adiwijaya, Elena Geretti, Victor Moyo, Kathy D Miller
BACKGROUND: This phase 1 dose-escalation trial studied MM-302, a novel HER2-targeted PEGylated antibody-liposomal doxorubicin conjugate, in HER2-positive locally advanced/metastatic breast cancer. METHODS: Patients were enrolled in four cohorts: MM-302 monotherapy (8, 16, 30, 40, and 50 mg/m2 every 4 weeks [q4w]); MM-302 (30 or 40 mg/m2 q4w) plus trastuzumab (4 mg/kg q2w); MM-302 (30 mg/m2 ) plus trastuzumab (6 mg/kg) q3w; MM-302 (30 mg/m2 ) plus trastuzumab (6 mg/kg) and cyclophosphamide (450 mg/m2 ) q3w...
October 26, 2018: British Journal of Cancer
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