+34 679 490 537info@nanbiosis.com

In vivo Characterization of Nanomedicines

Animal Facility-IVIS Spectrum equipment for bioluminiscence and fluorescence recording in whole-body mice
Animal Facility-IVIS Spectrum equipment for bioluminiscence and
fluorescence recording in whole-body mice

Scientific leaders of the project: Francisco Miguel Sánchez-Margallo, Verónica Crisóstomo, Beatriz Moreno, Simó Schwartz, José Luis Pedraz, Salvador Gil &Ramón Mangues.

Coordinator of the project: Ibane Abasolo & Francisco Miguel Sánchez-Margallo.

Industrial problem/gap covered

One of the causes that increase the time to market of nanotherapeutics is its preclinical validation. The standard protocols for more traditional drugs are not applicable for nanomedicines. NANBIOSIS offers a preclinical study plan tailored to meet the demands of each nanomedicine product, developed in collaboration with the user and starting from a set of basic analytical tests to more sophisticated experiments under either GLP and non-GLP conditions.

Description

Studies of nanomedicines are conducted in animals utilizing a variety of models and state of the arte imaging techniques (fluorescence, bioluminescence, TAC, MRI, CT, Echography, etc,) and a wide variety of analysis, including clinal tests: hematology, biochemistry, coagulation, urinalysis, tumor markers, hormones, fertility studies, cardiac markers, metabolic study. We collaborate in the selection of the most suitable animal species and can developexperimental pathology in different animal models (large white pig, sheep, goat, beagle dog, minipig, rabbit, rat and mouse) upon request.

Some examples are described in the following publications

Metronomic treatment in immunocompetent preclinical GL261 glioblastoma: effects of cyclophosphamide and temozolomide. Ferrer-Font L, Arias-Ramos N, Lope-Piedrafita S, Julià-Sapé M, Pumarola M,Arús C, Candiota AP. NMR Biomed. 2017Sep;30(9). doi: 10.1002/nbm.3748. Epub 2017 Jun 1. PubMed PMID: 28570014.

Pharmacokinetics of Benznidazole in Healthy Volunteers and Implications in Future Clinical Trials.Molina I, Salvador F, Sánchez-Montalvá A, Artaza MA, Moreno R, Perin L, Esquisabel A, Pinto L, Pedraz JL. Antimicrob Agents Chemother. 2017 Mar 24;61(4). pii: e01912-16. doi: 10.1128/AAC.01912-16. Print 2017 Apr.

Repeated dose toxicity study of Vibrio cholerae-loaded gastro-resistant microparticles.López Y, Pastor M, Infante JF, Díaz D, Oliva R, Fernández S, Cedré B, Hernández T, Campos L, Esquisabel A, Pedraz JL, Perez V, Talavera A. J Microencapsul. 2014;31(1):86-92. doi: 10.3109/02652048.2013.808278. Epub 2013 Jun 24.

Common swine models of cardiovascular disease for research and training. Crisóstomo V, Sun F, Maynar M, Báez-Díaz C, Blanco V, Garcia-Lindo M, Usón-Gargallo J, Sánchez-Margallo FM. Lab Anim (NY). 2016 Feb;45(2):67-74. doi: 10.1038/laban.935.

Delayed administration of allogeneic cardiac stem cell therapy for acute myocardial infarction could ameliorate adverse remodeling: experimental study in swine. Crisostomo V, Baez-Diaz C, Maestre J, Garcia-Lindo M, Sun F, Casado JG, Blazquez R, Abad JL, Palacios I, Rodriguez-Borlado L, Sanchez-Margallo FM. J Transl Med. 2015 May 12;13:156. doi: 10.1186/s12967-015-0512-2.

In the development of this biomedical solution, the following services are involved:

Efficacy

Efficacy studies of nanomaterial are conducted in animal utilizing a variety of models. We collaborate in the selection of the most suitable animal species and can developexperimental pathology in different animal models (large white pig, sheep, goat, beagle dog, minipig, rabbit, rat and mouse) upon request. At present we have some models of pathologies available:

Patology Animal Model Unit
Skin Wounds/skin regeneration Rat U10
Skin ulcers Diabeticpig, mouse U19, 21, 22 & 24
Diabeticulcers in cornea Rabitt U19, 21, 22 & 24
Any ulcer model Pig, mouse U19, 21, 22 & 24
Eye Ocular pathologies Rabbit U19, 21, 22 & 24
Diabetes Diabetes (Type II) Pig U19, 21, 22 & 24
Skin ulcers Diabetic pig, Rabit U19, 21, 22 & 24
Diabetic ulcers in cornea Rabitt U19, 21, 22 & 24
Bone Bone regeneration: calotte & hip Rat U10
Brain Alzheimer Mouse U10
Parkinson Rat U10
Cerebral ischemia Rat U19, 21, 22 & 24
Heart/Vascular Myocardial Infarction Pig U19, 21, 22 & 24
Vascular stenosis Pig U19, 21, 22 & 24
Arterial embolization Pig U19, 21, 22 & 24
Aneurysms Pig U19, 21, 22 & 24
Cancer Colorectal* immunodeficient mouse. Orthotopic, subcucaneous, intrasplenic. U18 & U20
Pancreas* immuno deficient mouse. Subcutaneous. U18
Endometrium Immuno deficient mouse. U18
Glioblastoma* Immunodeficient mouse. Orthotopic (steroatactic), subcucaneous. U18 & U20
Lymphoma* Immuno deficient mouse. U18
Leukemia* Immuno deficient mouse. U18
Prostate* Immuno deficient mouse. Orthotopic, subcucaneous. U20
Patient-derived tumor graft (PDX) models (Endometrium, colorectal) Immuno deficient mouse. U18
Breast (breast & Breast ductal carcinoma, adenocarcinoma & ductal adenocarcinoma,)* Orthotopic (Intramamary fat pad). U20
Cervix Subcutaneous. U20
Lung Subcutaneous. U20
Ewing sarcoma* Subcutaneous. U20
Skin: Melanoma* Subcutaneous & intravenous. U20
Glioblastoma Immuno competent mouse U25
Pseudotumors Pig U19, 21, 22 & 24
Inflammation Inflammation Rat (by LPS) U20
Digestive Hernias Pig U19, 21, 22 & 24
Colecystitis Pig U19, 21, 22 & 24
Genitourinary Urethral obstruction and stenosis/ endothelium inflammation Pig U19, 21, 22 & 24
Unilateral and bilateral cryptorchidism Dog U19, 21, 22 & 24
Benignprostatic hiperplasia Dog U19, 21, 22 & 24
Endometryosis Sheep U19, 21, 22 & 24

*Marked (luciferase, GFP, others)

Pharmacology and biodistribution

  • Pharmacokinetic; Animal studies in small and big animals to determine ADME (absorption, distribution, metabolism and excretion) studies.
  • Quantification of nanomedicines in fluids and biomarkers by ELISA
  • Validation and optimization of techniques
  • Biodistribution by MRI, luminescence, CT or echography
  • Studies in tissues by coupling hyperpolarization and MRI/MRS/MRSI at 7Tesla
  • Metabolomics studies in biofluid by NMR (14T)

Toxicity and Immunotoxicity

Single-Dose Acute Toxicity and Repeat-Dose Acute Toxicity Studies of anticancer nanomedicines in small animals U18 & U20
Histopathology in small animals U18
Single-Dose Acute Toxicity and Repeat-Dose Acute Toxicity Studies of nanomedicines in large animals U19, 21, 22 & 24
Histopathology in large animals U19, 21, 22 & 24
Detection immune response: detection of Antibodies (anti PEG and others) U2
PK of therapeutic antibodies U2

Mouse models for experimental oncology.

Nasal cavity.

1.5T MRI.