Impact of Nanobiotechnology on the

Future of Medicine (Nanomedicine):

The Road Toward Precision Medicine /
Case Studies

Shaker A. Mousa, PhD, MBA, FACC, FACB, FNAI

Professor of Pharmacology, Executive Vice President, and
Chairman of The Pharmaceutical Research Institute at Albany
College of Pharmacy and Health Sciences
Goal: From Nanomedicine to Precision Medicine
“Personalized Nanomedicine”

Precision
Medicine
Nano” From the Greek word for “dwarf” and means for 10-9, or
one billionth. In this case it refers to 10-9 meters, or 1
nanometer (nm).1 nm is about 3 atoms long.
Nano Synthesis, Design, Assembly and Characteristics
Bottom Up or Top Down
Could Enabling Technologies (Nanobiotechnology)
Accelerate and Improve DDD ?
 Existing Drugs:
1- Reformulation for Improved
PK PD, and Safety: (Oral
Insulin, Oral Proteins,
Combination of multiple RX).
2- Active Targeted
Delivery: Improved PG, PK, PD,
and Safety
(Chemotherapy, anti-microbial, anti-
Viral, Dyslipidemia,..)
 New Drugs:
1- Formulation for Improved
PK, PD, and Safety:
Vaccine, gene therapy, others
2- Active Targeted
Delivery: (Intra-cellular versus
extra-cellular)
Improved PG, PK, PD, and Safety
3- Bioimaging:
(Early Detection/ Monitoring)
 Case Studies
Nanomedicine in Drug Discovery and Development
(Shorten time, Mitigate Risk, Extend Product Life Cycle)
I) Reformulation for Improved PK and PD
(Nutraceuticals, Pharmaceuticals, and biopharma)
II) Devices for rapid and sustained Delivery
III) Nano-Targeted Drug Delivery for Improve
Efficacy and Safety (Chemotherapy, Anti-
microbial and Anti-viral, Dyslipidemia)
IV) Nanomedicine and Blood Brain Barrier – GBM, and Neuro delivery
V) Bioimaging (Functional Imaging)
 Classes of Active Pharmaceuticals (API) and impact of
Pharmaceutical Nanosystems
(Based on Solubility and Permeability)
Drug Classes II and IV

Low
Permeability IV
III
Passive vs. Active
Targeting
High

I II

High Low
Solubility
Correlation between the degree of solubility and permeability for the 4
Classes of Drugs - Class I and III have favorable solubility in contrast to
Classes II and IV.
In term of Permeability Class I and II have favorable permeability in
contrast to classes III and IV
 Reformulation of Wyeth’s Rapamune®
Improved BA + Improved Compliance
Nanoparticulate Suspension
• Improved oral BA by 27%
• Enabled preparation
of tablet
Enhanced patient convenience
and acceptability
• Improved patient choice
• Provided patent protection
(Product Life Cycle)
 Emend® (Aprepitant) Capsules (Based on
Nanoparticulate Suspension) – Substance P Antagonist

• Improved oral bioavailability

• Reduced fed/fasted variability in
bioavailability
Marketed Nanoparticulate Suspension Products
Efficacy/Safety PK
 Rapamune® by Wyeth in 2001; Oral Tablet
− Provides a stable tablet formulation (replaced a liquid dosage form) with 23% improvement
in bioavailability
− Easier storage—no refrigeration required
√
− More precise dosage/dosage linearity

 EMEND® by Merck in 2003; Oral Capsule

 Elimination of food requirement for drug (drug would otherwise have been abandoned) with
600% improvement in bioavailability
√
 TriCor® 145 by Fournier & Abbott, 2004; Oral Tablet
 Lower dose with 9% improvement in bioavailability
 Minimized food effect
√
 Patented formulation

 Megace® ES by Par, 2005 ; Oral Suspension

 Equivalent efficacy achieved with lower absolute dosage with 28% improvement in
bioavailability √
– Easier administration
– Lower API cost

 INVEGA® SUSTENNA® long-acting IM by Janssen, 2009

 1 month Intramuscular dosage form √ √
 Ease of administration & potential higher patient compliance

Liversidge E&G, ADDR, 2011, pg427 Basis of Filing

Robust, durable immunity by vaccination with single dose
adjuvant-free HBsAg Chitosan Nanoparticles

Robust serum anti-HBs titers in mice immunized with nanoparticle-encapsulated

HBsAg. BALB/c mice were immunized i.p. with a single injection of 1.5 g of soluble
free HBsAg (), nanoparticle-encapsulated HBsAg (), or HBsAg alum (). Weekly
serum samples were analyzed for anti-HBs levels by ELISA. *p<0.05 2-way ANOVA.
Mousa et al: Nanomedicine. 2013 Oct;9(7):923-34.
 Case Studies
Nanomedicine and Drug Discovery and Development
(Shorten time, Mitigate Risk, Extend Product Life Cycle)
I) Reformulation for Improved PK and PD
(Nutraceuticals, Pharmaceuticals, and biopharma)
II) Devices for rapid and sustained Delivery
III) Nano-Active Targeted Drug Delivery for
Improve Efficacy and Safety (Chemotherapy,
Anti-microbial and Anti-viral, Dyslipidemia)
IV) Nanomedicine and Blood Brain Barrier – GBM, and Neuro delivery
V) Bioimaging (Functional Imaging)
Abraxane (nab-paclitaxel) is a solvent-free ‘nano’ version of Taxol
(cremophor-based paclitaxel) – Passive Targeting

Abraxane Taxol

Abraxane received FDA

Approval 2005 for
metastatic breast cancer

NOW IT IS EXPANDED TO
VARIOUS TYPES OF
CANCER
Contents:
Contents: Paclitaxel 6 mg/ml
100 mg paclitaxel Cremophor 537 mg/ml
900 mg albumin Ethanol 396 mg/ml
No Surfactants/Solvents
 Thyrointegrin avb3
Receptors
Proangiogenic action of thyroid hormone is fibroblast growth factor-depe
ndent and is initiated at the cell surface.
Circ Res. 2004 Jun 11;94(11):1500-6.
Active Targeting Modalities [ Small Molecules,
Antibody, Aptamer, and others]

Example
Thyrointegrin avb3 receptors are
generously expressed by tumor cells and
rapidly-dividing blood vessel cells, enabling
us to target these cell populations with
Nano-Propyl Diamino tetrac to deliver
chemotherapies (Cisplatin, Paclitaxel)
.Nanomedicine (Lond) 2013 Dec;8(12):1943-54.
Angiogenesis. 2014 Jul;17(3):463-9.
 Increased cisplatin uptake by bladder
tumor by Nano-Diamino-tetrac targeted
Nanomedicinetreatment
(Lond). 2017;12(3):195-205.
120

**
Cisplatin level (ng/gm) + SEM

100
5 folds greater delivery with NDAT-
80 Cisplatin versus Cisplatin

60

40
*
20

0 Cisplatin Nanocisplatin Nanotetrac/cisplatin(tetrac)

* P < 0.05 Vs. Cisplatin, **P <0.0001 Vs. Cisplatin or Nano-cisplatin

Paclitaxel uptake in pancreatic (SUIT-2) tumors
After 3 weeks of treatment with paclitaxel, Nano-
paclitaxel or Nano-Diamino-tetrac-paclitaxel
Int. J Nanomedicine. 2017;12:1305-
1315 **
10 folds greater delivery with NDAT-Paclitaxel
versus 2 folds with Nab-Paclitaxel (Abraxane)

**P <0.001 versus paclitaxel or Nanopaclitaxel

Era of Personalized Medicines!
The Growth of Nanotechnology and its
applications is on the rise

2030
Nanomedicine and Future Advances
 Multi-functional Diagnostic Imaging and Therapeutic:
Matching a Tumor To a Drug (Personalize)
 Improve Efficacy and Safety of Existing and New Drugs
 Targeting the Immune System at tumor/micro-
environment
 Vaccine and Gene Therapy
 Biosensor and Auto-Medicine Delivery
 Biocompatible Implants and body parts (Tissue
Engineering and Regeneration)
“Increased Compliance, Improved Disease classifications,
Curative therapy and Improved Quality of Life”