The document discusses the development of a bisphosphonate-based osteotropic drug delivery system (BP-ODDS) for oral treatment of metastatic bone disease. Bisphosphonates effectively treat bone metastases but are only available intravenously due to poor oral bioavailability. The BP-ODDS uses myo-inositol hexakis and sodium dodecyl sulfate to increase bisphosphonate solubility in the gastrointestinal tract and enhance intestinal permeability, improving oral absorption. A comparative bioavailability study found the BP-ODDS achieved higher bisphosphonate levels than an intravenous drug formulation, demonstrating its effectiveness for oral treatment of bone metastases.
Objective: In order to reduce complications accompanied with dental implant restoration, this study strives to prepare a novel sealant and lubricant that can be used in dental implant systems as well as to evaluate its characteristics.
Study Design: Chitosan (CS), β-glycerophosphate pentahydrate (β-GP), and nano silver (nAg) were used to prepare thermosensitive hydrogel. According to the different volume ratios of CS to β-GP, 3 experimental groups were established, namely 16/4, 13/7, and 10/10 groups. Their morphology, composition, and chemical properties were analyzed via SEM, EDS, and FTIR. In addition, the effect of the hydrogel on the stability of dental implant-abutment connection was investigated by removal torque test combined with dynamic cyclic loading experiment. The maximum fracture load was measured under different lubricating conditions by electronic universal testing machine. The cytotoxicity and in vitro antibacterial effect of the hydrogel were examined respectively by CCK-8 test and the spread plate method.
Results: The CS/β-GP/nAg thermosensitive hydro-gel was successfully prepared in this study, which was found to be a porous structure through SEM. The removal torque test and the dynamic cyclic loading experiment showed that the removal torque of the experimental group was greater than that of the control group. Furthermore, the single load-to-fracture test indicated that the 16/4 group had the greatest maximum bearing load. The in vitro cytotoxicity test using rat bone marrow stromal cells (rBMSCs) and human gingival fibroblast cells (hGFCs) showed no cytotoxicity in all 3 groups. The 3 experimental groups had obvious antibacterial effects against E. coli, S. aureus, and P. gingivalis.
Conclusion: A nontoxic antibacterial CS/β-GP/nAg thermosensitive hydrogel for lubricating purpose was successfully fabricated. When the volume ratio of CS to β-GP was 16/4, this thermosensitive hydrogel demonstrated better sealing and lubricating abilities and had a positive influence on the reliability of dental implant-abutment connection.
Keywords: abutment, dental implant, dental implant restoration, dental sealant, lubrication, thermosensitive hydrogel
Objective: In order to reduce complications accompanied with dental implant restoration, this study strives to prepare a novel sealant and lubricant that can be used in dental implant systems as well as to evaluate its characteristics.
Study Design: Chitosan (CS), β-glycerophosphate pentahydrate (β-GP), and nano silver (nAg) were used to prepare thermosensitive hydrogel. According to the different volume ratios of CS to β-GP, 3 experimental groups were established, namely 16/4, 13/7, and 10/10 groups. Their morphology, composition, and chemical properties were analyzed via SEM, EDS, and FTIR. In addition, the effect of the hydrogel on the stability of dental implant-abutment connection was investigated by removal torque test combined with dynamic cyclic loading experiment. The maximum fracture load was measured under different lubricating conditions by electronic universal testing machine. The cytotoxicity and in vitro antibacterial effect of the hydrogel were examined respectively by CCK-8 test and the spread plate method.
Results: The CS/β-GP/nAg thermosensitive hydro-gel was successfully prepared in this study, which was found to be a porous structure through SEM. The removal torque test and the dynamic cyclic loading experiment showed that the removal torque of the experimental group was greater than that of the control group. Furthermore, the single load-to-fracture test indicated that the 16/4 group had the greatest maximum bearing load. The in vitro cytotoxicity test using rat bone marrow stromal cells (rBMSCs) and human gingival fibroblast cells (hGFCs) showed no cytotoxicity in all 3 groups. The 3 experimental groups had obvious antibacterial effects against E. coli, S. aureus, and P. gingivalis.
Conclusion: A nontoxic antibacterial CS/β-GP/nAg thermosensitive hydrogel for lubricating purpose was successfully fabricated. When the volume ratio of CS to β-GP was 16/4, this thermosensitive hydrogel demonstrated better sealing and lubricating abilities and had a positive influence on the reliability of dental implant-abutment connection.
Keywords: abutment, dental implant, dental implant restoration, dental sealant, lubrication, thermosensitive hydrogel
The Indian Dental Academy is the Leader in continuing dental education , training dentists in all aspects of dentistry and
offering a wide range of dental certified courses in different formats.for more details please visit
www.indiandentalacademy.com
In pharmacology,bisphosphonates (also called:diphosphonates) are a class of drugs that inhibit osteoclast action and the resorption of bone.
Its uses include the prevention and treatment of osteoporosis, osteitis deformans ("Paget's disease of bone"), bone metastasis (with or without hypercalcaemia), multiple myeloma and other conditions that feature bone fragility.
Objective: To evaluate the results of the effect of nebivolol on tibial bone defect and graft application in new bone development in the rat.
Study Design: Thirty Wistar albino rats were divided into 3 groups. In the Control group, tibia bone defect was created without any treatment. In the Defect+ Graft group, allograft treatment was performed by forming a 6 mm tibial bone defect. In the Defect+Graft+ Nebivolol group, alloplastic bone graft was placed in the calvarial bone defect and then nebivolol (0.34 mg/mL solution/day) treatment was intraperitoneally applied for 28 days.
Results: Histopathological examination revealed inflammation in the defect area, congestion in the vessels, degeneration in collagen fibers, and an increase in osteoclast cells. There was an increase in inflammation and blood vessel structure in graft application, and osteoblastic activity matrix formation after reorganization nebivolol application in collagen fibers. Osteonectin expression was positive in the collagen fiber and matrix, starting in the Graft group, in osteoblasts, whereas in the Nebivolol group, osteoblasts increased in osteocytes and new bone formation.
Conclusion: Nebivolol is thought to have a positive effect on osteoinductive bone growth factors and contribute to the cell-matrix interaction, in addition to the supporting effect of the graft with its antioxidative effect.
Keywords: allograft; bone; bone regeneration; disease models, animal; nebivolol; orthopedic procedures; osteonectin; rats; tibia; tibial defect
Bone replacement grafts are widely used to promote
bone formation and periodontal regeneration.
Xenografts are grafts shared between different species.
Currently, there are two available sources of xenografts
used as bone replacement grafts in periodontics: bovine
bone and natural coral.
The Indian Dental Academy is the Leader in continuing dental education , training dentists in all aspects of dentistry and offering a wide range of dental certified courses in different formats.
Indian dental academy provides dental crown & Bridge,rotary endodontics,fixed orthodontics,
Dental implants courses.for details pls visit www.indiandentalacademy.com ,or call
00919248678078
The Indian Dental Academy is the Leader in continuing dental education , training dentists in all aspects of dentistry and
offering a wide range of dental certified courses in different formats.for more details please visit
www.indiandentalacademy.com
In pharmacology,bisphosphonates (also called:diphosphonates) are a class of drugs that inhibit osteoclast action and the resorption of bone.
Its uses include the prevention and treatment of osteoporosis, osteitis deformans ("Paget's disease of bone"), bone metastasis (with or without hypercalcaemia), multiple myeloma and other conditions that feature bone fragility.
Objective: To evaluate the results of the effect of nebivolol on tibial bone defect and graft application in new bone development in the rat.
Study Design: Thirty Wistar albino rats were divided into 3 groups. In the Control group, tibia bone defect was created without any treatment. In the Defect+ Graft group, allograft treatment was performed by forming a 6 mm tibial bone defect. In the Defect+Graft+ Nebivolol group, alloplastic bone graft was placed in the calvarial bone defect and then nebivolol (0.34 mg/mL solution/day) treatment was intraperitoneally applied for 28 days.
Results: Histopathological examination revealed inflammation in the defect area, congestion in the vessels, degeneration in collagen fibers, and an increase in osteoclast cells. There was an increase in inflammation and blood vessel structure in graft application, and osteoblastic activity matrix formation after reorganization nebivolol application in collagen fibers. Osteonectin expression was positive in the collagen fiber and matrix, starting in the Graft group, in osteoblasts, whereas in the Nebivolol group, osteoblasts increased in osteocytes and new bone formation.
Conclusion: Nebivolol is thought to have a positive effect on osteoinductive bone growth factors and contribute to the cell-matrix interaction, in addition to the supporting effect of the graft with its antioxidative effect.
Keywords: allograft; bone; bone regeneration; disease models, animal; nebivolol; orthopedic procedures; osteonectin; rats; tibia; tibial defect
Bone replacement grafts are widely used to promote
bone formation and periodontal regeneration.
Xenografts are grafts shared between different species.
Currently, there are two available sources of xenografts
used as bone replacement grafts in periodontics: bovine
bone and natural coral.
The Indian Dental Academy is the Leader in continuing dental education , training dentists in all aspects of dentistry and offering a wide range of dental certified courses in different formats.
Indian dental academy provides dental crown & Bridge,rotary endodontics,fixed orthodontics,
Dental implants courses.for details pls visit www.indiandentalacademy.com ,or call
00919248678078
1. I.N.S.C.B. Institut Nord-Sud de Cooperation Biopharmaceutique
Th. Breul1, S. Silva-Lejmi1,
S. Rizea Savu2, & L. Silvestro2
1. I.N.S.C.B. – CNRS. France
2. 3S Pharmacological
Consultation & Research GmbH.
Germany
Presented at :
2nd Symposium of
Drug Delivery Systems
Nov. 8 –10 2012
Nanjing, China
Bone Targeting
Bisphosphonate based Osteotropic Drug Delivery System
for metastatic bone treatment by oral route
2. I.N.S.C.B. Institut Nord-Sud de Cooperation Biopharmaceutique
Bisphosphonate
based Osteotropic
Drug Delivery
System for
metastatic bone
treatment by
oral route
I INTRODUCTION
3. I.N.S.C.B. Institut Nord-Sud de Cooperation Biopharmaceutique
Many oncology patients with solid tumors
get secondary metastases to bone.
Current metastatic bone treatments are
bisphosphonates by intravenous route
(WorldWide sales > $ 1 billion)
Unmet medical need for patients treated by
regular infusions at hospitals / clinics
as no oral formulation is available
4. I.N.S.C.B. Institut Nord-Sud de Cooperation Biopharmaceutique
Bone : a complex organ
responsible for
structure, calcium storage
and hematopoïesis
Structure:
50-70% mineral
20-40 % organic matrix
5-10% water
1-5% lipids
Main component :
hydroxyapatite crystals
(HAP)
5. I.N.S.C.B. Institut Nord-Sud de Cooperation Biopharmaceutique
Bone turn-over : a bone remodeling cycle :
Osteoblastic bone formation
Osteoclastic bone resorption
Mineralization
6. I.N.S.C.B. Institut Nord-Sud de Cooperation Biopharmaceutique
Alteration of bone’s catabolism
and/or anabolism of bone diseases
Other pathologies:
osteosarcoma,
bone metastasis,
osteoarthritis,
osteomyelitis…
Osteoporosis :
bone resorption
> bone formation
8. I.N.S.C.B. Institut Nord-Sud de Cooperation Biopharmaceutique
Characteristics of Bone disease state : INFLAMATION
Enhanced Permeability & Retention (EPR)
Exposure of HAP to blood used to
deliver drugs to diseased tissue
9. I.N.S.C.B. Institut Nord-Sud de Cooperation Biopharmaceutique
Bone seeking agents
Tetracyclines
Mode of action :
Stop Protein elongation
via inhibition of aminoacyl-tRNA
Correct orientation of Tetracycline required to bind to HAP
Research of a minimalized tetracycline structure to reduce side effects
and retain capacity to bind to HAP
3-amino-2,6 dihydroxybenzamide
( 50 % ability to bind to HAP vs tetracycline)
10. I.N.S.C.B. Institut Nord-Sud de Cooperation Biopharmaceutique
Bone seeking agents
Acidic Oligopeptides
Bone SialoProtein (BSP) : Bone protein with high affinity to HAP
From BSP Acidic, Oligopeptides
with 4 to 10 AminoAcids
have been designed for
enhanced Biocompatibility
Based on Glutamic and Aspartic acids
In vivo trials :
i.v injection into mice of estradiol-17β-succinate-(L-Asp)6
affinities of AO depend only the number of AA,
not on their L or D characters or their species
11. I.N.S.C.B. Institut Nord-Sud de Cooperation Biopharmaceutique
Bone seeking agents :
BISPHOSPHONATES
The most studied
bone targeting
molecules
Mode of action : binding to
the inorganic part of HAP
12. I.N.S.C.B. Institut Nord-Sud de Cooperation Biopharmaceutique
BISPHOSPHONATES
First biological activity discovered in 1968
BPs’ strong affinity to HAP :
Retained even conjugated to other molecules
Relevant in bone scintigraphie
Use of Tc99 labeled methylene diphosphate (MDP)
or hydroxy methylene diphosphate (HDMP)
13. I.N.S.C.B. Institut Nord-Sud de Cooperation Biopharmaceutique
Advantages of using Bisphosphonates as
polymer/nanoparticle targeting moieties
Amino BP : primary amine
Can be conjugated to carboxylic acids
Conjugaison to nanomedecines via a degradable linker
Product of synergic effects when
coupled with appropriate drugs
+ Soon expiration of BPs’ patent protection
economic option
14. I.N.S.C.B. Institut Nord-Sud de Cooperation Biopharmaceutique
Bone Targeting using Bisphosphonates
Efficiency demonstrated in vivo with targeted
osteoprotegerin (OPG) as a model therapeutic protein
(M.R. Doshak, Mol. Pharmaceutics 6, (2009) 634-640)
Method :
Conjugaison
of OPG with a
« Bone seeking »
Thiol Bisphosphonate
Intravenous administration in a rat model of osteoarthritis
15. I.N.S.C.B. Institut Nord-Sud de Cooperation Biopharmaceutique
Results:
Delivery of
OPG-thiol-BP
to bone :
4 fold /
control OPG
in
osteoarthritis
rats
Significant advantage of BP conjugation as strategy in osteopenic
bone diseases
Targeting of control OPG and OPG-thiolBP
conjugates to femur and tibia in rats with osteoarthritis
Bone Targeting using Bisphosphonates
16. I.N.S.C.B. Institut Nord-Sud de Cooperation Biopharmaceutique
Bisphosphonates anti-angiogenic properties
most bone metastases are characterized by excess
osteoclast number and activity.
Some bisphosphonates, potent inhibitors
of osteoclast activity, are widely used for
prevention of bone metastases.
Bisphosphonates are also used to treat
hypercalcemia of malignancy,
osteosarcoma and multiple myeloma.
17. I.N.S.C.B. Institut Nord-Sud de Cooperation Biopharmaceutique
Bisphosphonates anti-angiogenic properties
Effects: apoptosis, inhibition of migration,
reduction of angiogenic sprouts of endothelial tissue
19. I.N.S.C.B. Institut Nord-Sud de Cooperation Biopharmaceutique
OSTEOTROPIC
DRUG DELIVERY SYSTEMS
A lot have
been studied !
20. I.N.S.C.B. Institut Nord-Sud de Cooperation Biopharmaceutique
OSTEOTROPIC DRUG DELIVERY SYSTEMS
The most studied polymer therapeutics to bone
Used in the design of micelles and dendrimers
Properties :
Biodistribution to bone
Bone targeting abilities
Low toxicity profile
In vivo data
HPMA copolymer – D-Asp8 conjugate: Administration i.v of
bone-targeted and non-targeted HPMA copolymers into mice
HPMA copolymer−alendronate (ALN) conjugate
I.V injection of conjugates with different Mw and ALN content into mice
21. I.N.S.C.B. Institut Nord-Sud de Cooperation Biopharmaceutique
All Osteotropic Drug Delivery Systems
Evaluated in vivo to date have been
administered intravenously
This is why a novel Bisphosphonate Osteotropic
Drug Delivery System (BP-ODDS) has been developed
by INSCB for ORAL ROUTE
to improve
Bisphosphonates oral bioavailability
…thereby enabling the development of
oral dosage forms for oncology indications.
22. I.N.S.C.B. Institut Nord-Sud de Cooperation Biopharmaceutique
Bisphophonates for cancer therapies
are administered intravenously by slow infusion.
Oral administration, is complicated by poor
bioavailability and poor gastrointestinal tolerability.
This limits their use in oncology to intravenous infusion
to achieve the doses required for efficacy.
Infusion of bisphosphonates is
however associated with dose
and infusion rate dependent
effects on renal function.
23. I.N.S.C.B. Institut Nord-Sud de Cooperation Biopharmaceutique
Bisphosphonates have very poor oral bioavailabilities :
0.6% in average !
Design of drug delivery systems enhancing oral
absorption is required for treatment efficiency !
24. I.N.S.C.B. Institut Nord-Sud de Cooperation Biopharmaceutique
INSCB proprietary technology combines
two factors affecting Bisphosphonates
physico-chemical and pharmacological behaviour in vivo
&… Their ability to form insoluble
calcium complexes in vivo in the GI tract
Their specific
transport through
intestinal
membrane
by paracellular
pathway
25. I.N.S.C.B. Institut Nord-Sud de Cooperation Biopharmaceutique
INSCB Bisphosphonate Osteotropic
Drug Delivery System : (BP-ODDS)
Two excipients, both registered at pharmacopeias and authorized for oral
administration were used to modulate these bisphosphonates properties
one calcium chelatant agent :
Myo-Inositol hexakis dihydrogen
phosphate dodecasodium
one intestinal
penetration enhancer :
Sodium Dodecyl Sulfate
26. I.N.S.C.B. Institut Nord-Sud de Cooperation Biopharmaceutique
Intestinal penetration enhancement :
Bisphosphonates
are highly
hydrophilic, they
can cross the
intestinal
membrane only
by using the
paracellular
pathway of
intestinal tight
junctions
Sodium Dodecyl sulfate increases intestinal permeability
by opening tight junctions, thus enhancing
paracellular absorption of Bisphosphonates
28. I.N.S.C.B. Institut Nord-Sud de Cooperation Biopharmaceutique
Physiological Calcium chelation
Myo-Inositol is a
stronger calcium
chelatant than
bisphosphonates
Its presence
increases
Bisphosphonate
solubility
in GI Tract
Bisphosphonates intestinal absorption Is enhanced
29. I.N.S.C.B. Institut Nord-Sud de Cooperation Biopharmaceutique
INSCB BP-ODDS
Manufacturing process
Classical physical dry mixture of excipients and drug substance
Can be processed in a film coated
tablet or in hard gelatine capsules.
Technology does not increase
manufacturing costs compared to
classical tablet or capsule production.
The new formulation shows no degradation
of the active drug after one year stability,
either in film coated tablet or hard gelatine capsule form
30. I.N.S.C.B. Institut Nord-Sud de Cooperation Biopharmaceutique
Comparative Bioavailability study
Purpose : To assess relative bioavailability of BP-ODDS,
vs reference formulation, a marketed film coated tablet
of a bisphosphonate (Actonel 35 mg ®),
Dose : 35 mg single dose, administered per os, one film-coated tablet of
35 mg with 200 ml of low carbonated water.
Subjects : 12 healthy volunteers in fasting conditions
Selection criteria : Male & female, aged 18-45, body mass index : 19 - 27.5
Methodology: Two period, two sequence, cross-over, block randomized
Duration of treatment : One day per period
Pharmacokinetic criteria for evaluation :
Risedronate AUC0-t , Cmax, AUC O-inf , Tmax + (T1/2 , MRT).
31. I.N.S.C.B. Institut Nord-Sud de Cooperation Biopharmaceutique
Comparative Bioavailability study
Comparative Bioavailability of BP-ODDS / INSCB
risedronate 35 mg vs marketed Actonel
0
20000
40000
60000
80000
100000
0 2 4 6 8 10 12
Time in Hours
Risedronatepg/ml
mean reference
Actonel (pg/ml)
mean test BP-ODDS /
INSCB (pg/ml)
33. I.N.S.C.B. Institut Nord-Sud de Cooperation Biopharmaceutique
CONCLUSIONS
Statistical analysis of pharmacokinetic data obtained proves that :
Test product : BP-ODDS / INSCB Sodium Risedronate 35 mg,
is relevantly better absorbed than reference ACTONEL® 35 mg
AUC of BP-ODDS is almost
300 % higher than reference Actonel®
Cmax of BP-ODDS is almost
500 % higher than reference Actonel®.
The Bisphosphonate Osteotropic Drug Delivery System
(BP-ODDS) developed, is supra-bioavailable
when compared to its reference marketed product
34. I.N.S.C.B. Institut Nord-Sud de Cooperation Biopharmaceutique
CONCLUSIONS
Tmax of BP-ODDS is half of Tmax of reference Actonel®
twice quicker efficiency for BP-ODDS.
Variability of primary pharmacokinetic parameters of
BP-ODDS are lower than variability of reference Actonel®
(20 % lower for C max and 60% lower for AUC 0-inf)
+ Safety :
BP-ODDS administered in single dose, orally,
was very well tolerated by the participant subjects.
35. I.N.S.C.B. Institut Nord-Sud de Cooperation Biopharmaceutique
BP-ODDS tablets or capsules offer a new paradigm for
metastatic bone cancer treatment
through the oral route
Their ability to better target growing metastatic tissues, cover an
unmet market need for oral bisphosphonates in oncology.
BP-ODDS is an effective and potentially safer alternative
to bisphosphonate intravenous infusions
which could offer the following advantages :
Improved quality of life for the patient
Cheaper treatment
Flexibility in the dosing regimen
36. I.N.S.C.B. Institut Nord-Sud de Cooperation Biopharmaceutique
BP-ODDS could also be used as a
carrier for drugs needing vectorization to bone
Either using the
Micelle forming
ability of some
bisphosphonates
to carry the drug
candidate
Or by use of a
biodegradable linker
to be conjugated
to a bisphosphonate
or a bisphosphonic group
37. I.N.S.C.B. Institut Nord-Sud de Cooperation Biopharmaceutique
This Osteotropic Drug Delivery System
has been patented by INSCB in 2011
and is available for license
Contact : contact@inscb.org
40. I.N.S.C.B. Institut Nord-Sud de Cooperation Biopharmaceutique
Bone seeking agents
Estradiol analogs
Localisation in bone tissue + lack of estrogenic properties
Methods : Attaching calcium chelators to an estradiol moiety
via succinoyl or carboxyethyl linkers
Improvement of targeting potential
41. I.N.S.C.B. Institut Nord-Sud de Cooperation Biopharmaceutique
Amino BP: disturbance of mevalonate pathway
inhibition of protein prenylation
and osteoclasts’ loss of function
Non amino BP: creation of a modified ATP
inability to be hydrolysed
Osteoclasts’ apoptosis and
reduced bone turn-over
More potent
2 sorts of Bisphosphonates
42. I.N.S.C.B. Institut Nord-Sud de Cooperation Biopharmaceutique
Comparative bone seeking properties of
Bisphosphonates (BP) Acidic Oligopeptides (AO)
and Tetracycline
Rate of binding to HAP : Faster for AO than BP due to
a larger binding area of AO
Binding strength : Greater for BP than AO due to
a higher specificity of BP for HAP
Binding sites : - All bone for BP
- Higher cristalline HAP for AO
- Growing surfaces with low cristallinity
for Tetracycline
43. I.N.S.C.B. Institut Nord-Sud de Cooperation Biopharmaceutique
Bone targeting principles
Osteoclast targeting :
Use of BP and AO because of their favored binding onto absorbing
surfaces
Osteoblast targeting :
Use of Tetracyclines or analogs because of their favored binding on
bone’s growing surfaces
44. I.N.S.C.B. Institut Nord-Sud de Cooperation Biopharmaceutique
Comparative Bioavailability study
Methodology:
Two period, two sequence, cross-over, block randomized
Hospitalization of subjects : until 24 hours post administration.
Washout period : 46 days.
Blood samplings collected : Before dose (0.0) & 20 sampling points
Post dose from 0.25, to 168.0 hours.
Analytical method : Determination of Risedronate in plasma
by HPLC- MS/MS.
Comparative bioavailability assessment based on plasma
drug levels of test bisphosphonate used, (sodium risedronate).
+ Safety : Laboratorv data / Vital signs / Adverse events
45. I.N.S.C.B. Institut Nord-Sud de Cooperation Biopharmaceutique
RESULTS: Pharmacokinetics parameters :
Mean pharmacokinetics characteristics of risedronic acid after treatment with
REFERENCE : Actonel ® and TEST : BP-ODDS / INSCB products
Comparative bioavailability of the primary parameters (test name : Classic 90% CI) :
Parameter AUC 0-t AUC 0-inf C max T max
Test Value
(Test / Reference)
295.854 266.363 480.004 0.530
Comparative coefficients of variation (CV) of the primary pharmacokinetic parameters
Parameter AUC 0-t AUC 0-inf C max
Test Value
(CV Test / CV Reference)
0.85 0.38 0.79
46. I.N.S.C.B. Institut Nord-Sud de Cooperation Biopharmaceutique
Future of the field
Development of bone targeted anti-neoplastic agents
Because bone metastases = unsolved problem in oncology
Research about bone targeted therapeutics focusing on:
EPR effect , Delivery of siRNA to solid tumors
Combination therapies: (i.e : Paclitaxel / BP; Statins : BP…)
bone targeting of relevant drugs in order to reduce pain
+ improve quality of life
Continous increase in prevalence
of bone diseases with aging population
47. I.N.S.C.B. Institut Nord-Sud de Cooperation Biopharmaceutique
Many novel drug applications: yet to be explored
Better development of disease specific targeting
Research of bone conditions present in each disease + targeting
mechanisms
Discovery of specific biochemical pathways => disease states