Improved stability and antidiabetic potential of insulin containing folic acid functionalized polymer stabilized multilayered liposomes following oral administration
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Improved stability and antidiabetic potential of insulin containing folic acid functionalized polymer stabilized multilayered liposomes following oral administration. / Agrawal, Ashish Kumar; Harde, Harshad; Thanki, Kaushik; Jain, Sanyog.
In: Biomacromolecules, Vol. 15, No. 1, 13.01.2014, p. 350-60.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Improved stability and antidiabetic potential of insulin containing folic acid functionalized polymer stabilized multilayered liposomes following oral administration
AU - Agrawal, Ashish Kumar
AU - Harde, Harshad
AU - Thanki, Kaushik
AU - Jain, Sanyog
PY - 2014/1/13
Y1 - 2014/1/13
N2 - The present study reports the folic acid (FA) functionalized insulin loaded stable liposomes with improved bioavailability following oral administration. Liposomes were stabilized by alternating coating of negatively charged poly(acrylic acid) (PAA) and positively charged poly(allyl amine) hydrochloride (PAH) over liposomes. Furthermore, folic acid was appended as targeting ligand by synthesizing folic acid-poly(allyl amine) hydrochloride conjugate. The insulin entrapped within the freeze-dried formulation was found stable both chemically as well as conformationally and developed formulation exhibited excellent stability in simulated biological fluids. Caco-2 cell and ex vivo intestinal uptake studies revealed higher uptake of folic acid functionalized layersomes in comparison with their plain counterparts. In vivo pharmacodynamic and pharmacokinetic studies further revealed almost double hypoglycemia and approximately 20% relative bioavailability in comparison with subcutaneously administered standard insulin solution. Overall the proposed strategy is expected to contribute significantly in the field of designing ligand-anchored, polyelectrolyte-based stable systems in drug delivery.
AB - The present study reports the folic acid (FA) functionalized insulin loaded stable liposomes with improved bioavailability following oral administration. Liposomes were stabilized by alternating coating of negatively charged poly(acrylic acid) (PAA) and positively charged poly(allyl amine) hydrochloride (PAH) over liposomes. Furthermore, folic acid was appended as targeting ligand by synthesizing folic acid-poly(allyl amine) hydrochloride conjugate. The insulin entrapped within the freeze-dried formulation was found stable both chemically as well as conformationally and developed formulation exhibited excellent stability in simulated biological fluids. Caco-2 cell and ex vivo intestinal uptake studies revealed higher uptake of folic acid functionalized layersomes in comparison with their plain counterparts. In vivo pharmacodynamic and pharmacokinetic studies further revealed almost double hypoglycemia and approximately 20% relative bioavailability in comparison with subcutaneously administered standard insulin solution. Overall the proposed strategy is expected to contribute significantly in the field of designing ligand-anchored, polyelectrolyte-based stable systems in drug delivery.
KW - Administration, Oral
KW - Animals
KW - Caco-2 Cells
KW - Diabetes Mellitus, Experimental
KW - Drug Delivery Systems
KW - Drug Stability
KW - Folic Acid
KW - Humans
KW - Insulin
KW - Liposomes
KW - Male
KW - Polymers
KW - Rats
KW - Rats, Sprague-Dawley
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
U2 - 10.1021/bm401580k
DO - 10.1021/bm401580k
M3 - Journal article
C2 - 24283460
VL - 15
SP - 350
EP - 360
JO - Biomacromolecules
JF - Biomacromolecules
SN - 1525-7797
IS - 1
ER -
ID: 168217690