Nanotechnology and Insulin: A Perfect Marriage? - PowerPoint PPT Presentation

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Nanotechnology and Insulin: A Perfect Marriage?

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The s would highlight the some of the recent developments in the field of nanobiotechnology regarding non-parenteral insulin delivery – PowerPoint PPT presentation

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Title: Nanotechnology and Insulin: A Perfect Marriage?


1
NANOTECHNOLOGY AND INSULIN A PERFECT
MARRIAGE ????
Awanish Kumar, Ashwini Kumar Department of
Biotechnology NIT Raipur
Presented By Ashwini Kumar Doctoral Research
Scholar Department of Biotechnology National
Institute of Technology (NIT) Raipur C.G
2
Diabetes..
  • gt 550 million by 2030 (WHO)
  • IDDM and NIDDM
  • Hyperglycemia
  • CVD, Retinopathy, Neuropathy, Nephropathy,
    Pulmonary Disorders, Infections..
  • Oral Sulfonylureas, Biguanides, TZDs,
    a-glucosidase inhibitors, Incretin analogs, DPP-4
    inhibitors, SGLT2 inhibitors, GSK-3
    inhibitors..
  • Parenteral Subcutaneous Insulin

3
Insulin..
  • Peptide hormone (51 a.a) secreted by ß-cells of
    the pancreas.
  • Regulates the blood glucose level by transporting
    glucose inside adipocytes and skeletal muscles
    for further use.
  • Recombinant Human Insulin (rHI) is currently the
    final answer to the uncontrolled diabetes (type 1
    and type 2).
  • Formulations Short acting, Intermediate acting,
    Long acting, Ultra long acting.
  • Regulates pre-prandial and post-prandial blood
    glucose.
  • Parenteral (sub-cutaneous) administration.
  • Injection site morbidity comes as resistance.

4
Alternatives..
5
Inhaled Insulin Formulations
  • Lungs are highly vascularized, surface area
    50-140 m2 .
  • Thin alveolar-capillary barrier, rapid
    absorption.
  • No peptidases or proteases
  • No pH variation
  • Enhanced absorption with particle size 1-3µm in
    diameter larger particles are often swollowed
    through upper respiratory tract.
  • Dry powder (Exubera and Technosphere) and Liquid
    (AERx iDMS).

6
A. Exubera
  • Pfizer/Nektar Pharmaceuticals
  • Dry powder formulation
  • First ever non-parenteral insulin reached market
    in 2006 withdrawn in late 2007
  • Peak insulin concentration more quickly than
    sub-cutaneous route (45 minutes vs. 105 minutes).
  • Spray-dried (lyophilized) excipients were
    mannitol, glycine, sodium citrate.
  • 1 unit (3 mg) insulin or 3 units insulin per
    blister particle diameter lt 5 µm.

7
Drawbacks of Exubera
  • Not suitable for smokers, asthamatic patients
    COPD patients.
  • Lung deposition.
  • Decreased the respiratory volumes.
  • A few patients were diagnosed with pulmonary
    malignancy (IGF-1 activity)
  • Low market acceptibility

8
B. Afrezza
  • Developed by MannKind Corp. CA (USA) Approved by
    USFDA in June 2014.
  • Technosphere Insulin (TI) rHI combined with
    fumaryl diketopiperazine.
  • Technosphere particles were prepared by pH
    controlled crystallization of FDKP, polysorbate
    80, acetic acid and water.
  • Median particle size 2-2.5 micron (µm)
  • FDKP and Insulin are absorbed independently
    former excreted unchanged in urine.

9
Contd..
  • Insulin release mimics the pancreatic release
    pattern.
  • Median Tmax from lungs to blood is 15 minutes.
  • TI was found to ne non-cytotoxic to the bronchial
    cell lines (no membrane or tight junction
    damage).
  • Hypoglycemic and weight gain events lesser than
    the SC injection.
  • Better result in COPD and pulmonary patients as
    compared to Exubera, but still should be used
    with utmost precaution.

10
Advantages..
  • Better bioavailibility no 1st pass metabolism
  • Ease of access
  • Easy storage and transportaion
  • No chance of microbial contamination

11
Oral Insulin Formulations..
  • Insulin is a peptide !!!!
  • PROTEASE INHIBITORS (trypsin, chymotrypsin,
    elastase, carboxypeptidase, aminopeptidase,
    insulin degrading enzymes).
  • pH variation, chemical degradation (1-7.5)
  • Must adhere to the mucus layer..MUCOADHESIVE
  • Intestinal cell permeability (hydrophillic
    large MW)..ABSORPTION and PERMEATION ENHANCERS
    (ZOT 4-CNAB).

12
Oral Insulin Formulations..
OI FORMULATION COMPANY PHASE
ORMD 0801 Enteric coated, Protease inhibitors, Absorption Enhancers, Capsule Oramed Pharmaceuticals Israel III
IN-105 Conjugated at B29 lysine with PEG via acetyl chain, tablet Biocon Bristol Myers III
CAPSULIN Enteric coated capsules Diabetology UK IIa
DIASOME Hepatic Directed Visecles (HDV) liposomes loaded with Insulin and Hepatocyte Target Molecule (HTM) attached Diasome, USA II
NN1954 GIPET Technology medium chain fatty acids, Novo Nordisk Merrion Pharmaceuticals II
13
Advantages..
  • Easiest way of delivery.
  • Low immunogenecity
  • Low mitogenecity
  • Low dosage forms and good bioavailibility

14
NIDDK Study
15
On-going Experiments..
  • Chitosan, Alginate, Chitosan-Alginate, Liposomes,
    Dextran, Pectin, Cyclodextrin
  • PLGA (FDA approved), PLA, PCL, Poly Acrylic Acid
    (PAA)
  • Thiolated chitosan, better mucoadhesive and
    extended drug release.
  • PAA-Cys Mucoadhesive, permeation enhancer,
    protease protection.
  • PolyElectrolyte Complexes (PECs) by mixing
    oppositely charged ions

16
C. Buccal Insulin
  • Aerosol spray in the oralpharyngeal cavity.
  • Presystemic metabolism in GIT and Liver is
    avoided.
  • Better accessibility
  • Low pH variation
  • Good surface area
  • Only animal for test is pig

17
Oral- Lyn
  • Generex Biotechnology, Ontaraio, Canada
  • Aerosol insulin preparation.
  • Average produced micelles is gt 10 µm so cant go
    to lungs.
  • Each puff 10 U insulin stable at RT for approx 6
    months
  • Surfactant, solubilizer, micelles forming agent.
  • Appear in circulation within 5-10 minutes after
    administration.
  • Short Tmax and faster time to peak glucose
    uptake than SC route.

18
Withdrawn !!!!
  • AutoImmune, Biosante, Coremed, Eligen, Nobex in
    phase II trials.
  • Aerodose (by Aerogen)
  • Unknown (by Abott)
  • HIIP (Eli Lilly)
  • Alveair (Coremed)
  • BioAir (Biosante)
  • Unknown (Epic Therapeutics)
  • Spiros (Elan Pharmaceuticals)

19
Why Nanotechnology ????
  • Better than conventional drug loading, delivery
  • Large diabetic population and increasing
  • Large scope
  • Easy for difficult molecules (peptides and
    proteins)

20
  • THANK YOU
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