Controlled-release components of PZP contraceptive vaccine extend duration of infertility

2008 ◽  
Vol 35 (6) ◽  
pp. 555 ◽  
Author(s):  
John W. Turner ◽  
Allen T. Rutberg ◽  
Ricky E. Naugle ◽  
Manpreet A. Kaur ◽  
Douglas R. Flanagan ◽  
...  

Successful immunocontraception of wildlife relying on repeated access to individuals for boosters has highlighted the need to incorporate primer and booster immunisations into one injection. We have investigated use of controlled-release polymers (lactide–glycolide) in small pellets to provide delayed in vivo delivery of booster porcine zona pellucida (PZP) antigen and adjuvant. This report reviews pellet-making methodology, in vitro testing of controlled-release pellets and in vivo effects of controlled-release PZP vaccine. We assessed 3 different manufacturing approaches for producing reliable, cost-effective pellets: (1) polymer melting and extrusion; (2) solvent evaporation from polymer solution; and (3) punch and die polymer moulding. In vitro testing of release patterns of controlled-release formulations, towards development of a 3-year duration vaccine, provided estimates for in vivo use of pellet preparations. These in vitro studies demonstrated protein release delay up to 22 months using 100% l-lactide or polycaprolactone polymers. For in vivo tests, pellets (1-, 3-, and 12-month release delay) serving as boosters were administered intramuscularly with PZP/adjuvant liquid primer to wild horses (Equus caballus), white-tailed deer (Odocoileus virginanus) and African elephants (Loxodonta africana). Horse field studies assessed fertility via offspring counts and/or faecal-hormone pregnancy testing. Treatment decreased fertility 5.3–9.3-fold in Year 1 and 3.6-fold in Year 2. In preliminary testing in deer, offspring counts revealed treatment-associated fertility reduction of 7.1-fold Year 1 and 3.3-fold Year 2. In elephants, treatment elevated anti-PZP titres 4.5–6.9-fold from pretreatment (no fertility data).

2018 ◽  
Vol 18 (5) ◽  
pp. 321-368 ◽  
Author(s):  
Juan A. Bisceglia ◽  
Maria C. Mollo ◽  
Nadia Gruber ◽  
Liliana R. Orelli

Neglected diseases due to the parasitic protozoa Leishmania and Trypanosoma (kinetoplastids) affect millions of people worldwide, and the lack of suitable treatments has promoted an ongoing drug discovery effort to identify novel nontoxic and cost-effective chemotherapies. Polyamines are ubiquitous small organic molecules that play key roles in kinetoplastid parasites metabolism, redox homeostasis and in the normal progression of cell cycles, which differ from those found in the mammalian host. These features make polyamines attractive in terms of antiparasitic drug development. The present work provides a comprehensive insight on the use of polyamine derivatives and related nitrogen compounds in the chemotherapy of kinetoplastid diseases. The amount of literature on this subject is considerable, and a classification considering drug targets and chemical structures were made. Polyamines, aminoalcohols and basic heterocycles designed to target the relevant parasitic enzyme trypanothione reductase are discussed in the first section, followed by compounds directed to less common targets, like parasite SOD and the aminopurine P2 transporter. Finally, the third section comprises nitrogen compounds structurally derived from antimalaric agents. References on the chemical synthesis of the selected compounds are reported together with their in vivo and/or in vitro IC50 values, and structureactivity relationships within each group are analyzed. Some favourable structural features were identified from the SAR analyses comprising protonable sites, hydrophobic groups and optimum distances between them. The importance of certain pharmacophoric groups or amino acid residues in the bioactivity of polyamine derived compounds is also discussed.


Nanophotonics ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 3023-3034
Author(s):  
Weiyuan Liang ◽  
Dou Wang ◽  
Xiaohui Ren ◽  
Chenchen Ge ◽  
Hanyue Wang ◽  
...  

AbstractTwo-dimensional black phosphorus (BP) has been demonstrated to be promising in photoelectronic devices, electrode materials, and biomedicine owing to its outstanding properties. However, the application of BP has been hindered by harsh preparation conditions, high costs, and easy degradation in ambient condition. Herein, we report a facile and cost-effective strategy for synthesis of orthorhombic phase BP and a kind of BP-reduced graphene oxide (BP/rGO) hybrids in which BP remains stable for more than 4 weeks ascribed to the formation of phosphorus-carbon covalent bonds between BP and rGO as well as the protection effect of the unique wrinkle morphology of rGO nanosheets. Surface modification BP/rGO hybrids (PEGylated BP/rGO) exhibit excellent photothermal performance with photothermal conversion efficiency as high as 57.79% at 808 nm. The BP/rGO hybrids exhibit enhanced antitumor effects both in vitro and in vivo, showing promising perspectives in biomedicine.


2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Zeping Qiu ◽  
Jingwen Zhao ◽  
Fanyi Huang ◽  
Luhan Bao ◽  
Yanjia Chen ◽  
...  

AbstractMyocardial fibrosis and ventricular remodeling were the key pathology factors causing undesirable consequence after myocardial infarction. However, an efficient therapeutic method remains unclear, partly due to difficulty in continuously preventing neurohormonal overactivation and potential disadvantages of cell therapy for clinical practice. In this study, a rhACE2-electrospun fibrous patch with sustained releasing of rhACE2 to shape an induction transformation niche in situ was introduced, through micro-sol electrospinning technologies. A durable releasing pattern of rhACE2 encapsulated in hyaluronic acid (HA)—poly(L-lactic acid) (PLLA) core-shell structure was observed. By multiple in vitro studies, the rhACE2 patch demonstrated effectiveness in reducing cardiomyocytes apoptosis under hypoxia stress and inhibiting cardiac fibroblasts proliferation, which gave evidence for its in vivo efficacy. For striking mice myocardial infarction experiments, a successful prevention of adverse ventricular remodeling has been demonstrated, reflecting by improved ejection fraction, normal ventricle structure and less fibrosis. The rhACE2 patch niche showed clear superiority in long term function and structure preservation after ischemia compared with intramyocardial injection. Thus, the micro-sol electrospun rhACE2 fibrous patch niche was proved to be efficient, cost-effective and easy-to-use in preventing ventricular adverse remodeling.


1984 ◽  
Vol 11 (5) ◽  
pp. 279-282 ◽  
Author(s):  
Robert L. Rietschel ◽  
Ronald Muggins ◽  
Nicole Levy ◽  
Pat M. Pruitt

1991 ◽  
Vol 18 ◽  
pp. 5-11 ◽  
Author(s):  
F. Baquero ◽  
C. Patrón ◽  
R. Cantón ◽  
M.Martínez Ferrer
Keyword(s):  

Author(s):  
Ashish Patel ◽  
Ravi Vanecha ◽  
Jay Patel ◽  
Divy Patel ◽  
Umang Shah ◽  
...  

: Cancer is a frightful disease that still poses a 'nightmare' worldwide, causing millions of casualties annually due to one of the human race's most significant healthcare challenges that requires a pragmatic treatment strategy. However, plants and plant-derived products revolutionize the field as they are quick, cleaner, eco-friendly, low-cost, effective, and less toxic than conventional treatment methods. Plants are repositories for new chemical entities and have a promising cancer research path, supplying 60% of the anticancer agents currently used. Alkaloids are important chemical compounds that serve as a rich reservoir for drug discovery and development. However, some alkaloids derived from natural herbs display anti-proliferation and antimetastatic activity on different forms of cancer, both in vitro and in vivo. Alkaloids have also been widely formulated as anticancer medications, such as camptothecin and vinblastine. Still, more research and clinical trials are required before final recommendations can be made on specific alkaloids. This review focuses on the naturally-derived bioactive alkaloids with prospective anticancer properties based on the information in the literature.


2021 ◽  
Author(s):  
Eszter Lakatos ◽  
Helen Hockings ◽  
Maximilian Mossner ◽  
Michelle Lockley ◽  
Trevor A. Graham

AbstractCell-free DNA (cfDNA) measured via liquid biopsies provides a way for minimally-invasive monitoring of tumour evolutionary dynamics during therapy. Here we present liquidCNA, a method to track subclonal evolution from longitudinally collected cfDNA samples based on somatic copy number alterations (SCNAs). LiquidCNA utilises SCNA profiles derived through cost-effective low-pass whole genome sequencing to automatically and simultaneously genotype and quantify the size of the dominant subclone without requiring prior knowledge of the genetic identity of the emerging clone. We demonstrate the accuracy of liquidCNA in synthetically generated sample sets and in vitro and in silico mixtures of cancer cell lines. Application in vivo in patients with metastatic lung cancer reveals the progressive emergence of a novel tumour sub-population. LiquidCNA is straightforward to use, computationally inexpensive and enables continuous monitoring of subclonal evolution to understand and control therapy-induced resistance.


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