PMID- 16777255
OWN - NLM
STAT- MEDLINE
DCOM- 20060929
LR  - 20181113
IS  - 0168-3659 (Print)
IS  - 0168-3659 (Linking)
VI  - 113
IP  - 2
DP  - 2006 Jun 28
TI  - The quest for non-invasive delivery of bioactive macromolecules: a focus on 
      heparins.
PG  - 91-101
AB  - The development of a non-invasive drug delivery system for unfractionated heparin 
      (UFH) and low molecular weight heparins (LMWHs) has been the elusive goal of 
      several research groups since the initial discovery of this glycosaminogylcan by 
      McLean in 1916. After a brief update on current parenteral formulations of UFH 
      and LMWHs, this review revisits past and current strategies intended to identify 
      alternative routes of administration (e.g. oral, sublingual, rectal, nasal, 
      pulmonary and transdermal). The following strategies have been used to improve 
      the bioavailability of this bioactive macromolecule by various routes: (i) 
      enhancement in cell-membrane permeabilization, (ii) modification of the 
      tight-junctions, (iii) increase in lipophilicity and (iv) protection against 
      acidic pH of the stomach. Regardless of the route of administration, a simplified 
      unifying principle for successful non-invasive macromolecular drug delivery may 
      be: "to reversibly overcome the biological, biophysical and biochemical barriers 
      and to safely and efficiently improve the in vivo spatial and temporal control of 
      the drug in order to achieve a clinically acceptable therapeutic advantage". 
      Future macromolecular drug delivery research should embrace a more systemic 
      approach taking into account recent advances in genomics/proteomics and 
      nanotechnology.
FAU - Motlekar, Nusrat A
AU  - Motlekar NA
AD  - Department of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University 
      Health Sciences Center, Amarillo, TX 79106, USA.
FAU - Youan, Bi-Botti C
AU  - Youan BB
LA  - eng
GR  - R15 GM069397/GM/NIGMS NIH HHS/United States
GR  - GM 069397-01A2/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Review
DEP - 20060614
PL  - Netherlands
TA  - J Control Release
JT  - Journal of controlled release : official journal of the Controlled Release 
      Society
JID - 8607908
RN  - 0 (Macromolecular Substances)
RN  - 9005-49-6 (Heparin)
SB  - IM
MH  - Animals
MH  - Drug Administration Routes
MH  - Drug Delivery Systems/*methods
MH  - Heparin/*administration & dosage
MH  - Humans
MH  - Macromolecular Substances/administration & dosage
PMC - PMC1539865
MID - NIHMS11469
EDAT- 2006/06/17 09:00
MHDA- 2006/09/30 09:00
PMCR- 2008/01/28
CRDT- 2006/06/17 09:00
PHST- 2006/02/22 00:00 [received]
PHST- 2006/04/06 00:00 [accepted]
PHST- 2006/06/17 09:00 [pubmed]
PHST- 2006/09/30 09:00 [medline]
PHST- 2006/06/17 09:00 [entrez]
PHST- 2008/01/28 00:00 [pmc-release]
AID - S0168-3659(06)00175-1 [pii]
AID - 10.1016/j.jconrel.2006.04.008 [doi]
PST - ppublish
SO  - J Control Release. 2006 Jun 28;113(2):91-101. doi: 10.1016/j.jconrel.2006.04.008. 
      Epub 2006 Jun 14.