PMID- 29859807
OWN - NLM
STAT- MEDLINE
DCOM- 20181024
LR  - 20181024
IS  - 1873-3441 (Electronic)
IS  - 0939-6411 (Linking)
VI  - 129
DP  - 2018 Aug
TI  - Anhydrous thiomers: Strategy for enhanced mucoadhesion.
PG  - 273-281
LID - S0939-6411(18)30197-8 [pii]
LID - 10.1016/j.ejpb.2018.05.038 [doi]
AB  - AIM: The aim of this study was to evaluate the impact of the absence of water 
      during the synthesis of thiolated poly(acrylic acid) (PAA) on its mucoadhesive 
      properties. Previously, thiolation of hydrophilic polymers was performed in 
      aqueous media, where (poly)acrylates undergo a conformational transition to form 
      an entangled network of polymer chains stabilized by neutralization. The impact 
      of chain entanglement, porosity and degree of functionalization of anhydrous 
      precipitated polymers on their mucoadhesive characteristics were therefore 
      evaluated in comparison to the equivalent products synthesized in water and dried 
      by lyophilization. METHODS: Anhydrous synthesis and purification procedures were 
      designed for the thiolation and entire preactivation of PAA by means of 
      immobilization of l-cysteine (PAA-Cys) and 2-mercaptonicotinic acid 
      (PAA-Cys-MNA), respectively. The obtained conjugates were characterized 
      chemically and for their particle size. Differences in mucoadhesive properties 
      were determined by means of the residence time as well as tensile strength of 
      polymer test disks on porcine small intestinal mucosa. RESULTS: Anhydrous 
      products revealed a 4.2-fold higher amount of immobilized free thiol moieties for 
      PAA-Cys and a 3.1-fold higher quantity of 2-mercaptonicotinic acid for 
      PAA-Cys-MNA. The impact of particle size of anhydrous products on their 
      mucoadhesive properties was negligible. In comparison to the corresponding 
      aqueous products a 2.5-fold increase in residence time for PAA-Cys and 21.2-fold 
      increase for PAA-Cys-MNA was achieved and in agreement with these results, the 
      improvement in the total work of adhesion was 2.9-fold for PAA-Cys and 5.1-fold 
      for PAA-Cys-MNA. CONCLUSION: According to these findings, anhydrous synthesis 
      conditions seem to be a promising tool for improved modification rates and 
      moreover enhanced mucoadhesive properties of hydrophilic polymers.
CI  - Copyright (c) 2018 Elsevier B.V. All rights reserved.
FAU - Baus, Randi Angela
AU  - Baus RA
AD  - Center for Chemistry and Biomedicine, Department of Pharmaceutical Technology, 
      Institute of Pharmacy, Leopold-Franzens-University of Innsbruck, Innrain 80/82, 
      6020 Innsbruck, Austria.
FAU - Innerhofer, Julia
AU  - Innerhofer J
AD  - Center for Chemistry and Biomedicine, Department of Pharmaceutical Technology, 
      Institute of Pharmacy, Leopold-Franzens-University of Innsbruck, Innrain 80/82, 
      6020 Innsbruck, Austria.
FAU - Rohrer, Julia
AU  - Rohrer J
AD  - Center for Chemistry and Biomedicine, Department of Pharmaceutical Technology, 
      Institute of Pharmacy, Leopold-Franzens-University of Innsbruck, Innrain 80/82, 
      6020 Innsbruck, Austria.
FAU - Lupo, Noemi
AU  - Lupo N
AD  - Center for Chemistry and Biomedicine, Department of Pharmaceutical Technology, 
      Institute of Pharmacy, Leopold-Franzens-University of Innsbruck, Innrain 80/82, 
      6020 Innsbruck, Austria.
FAU - Bernkop-Schnurch, Andreas
AU  - Bernkop-Schnurch A
AD  - Center for Chemistry and Biomedicine, Department of Pharmaceutical Technology, 
      Institute of Pharmacy, Leopold-Franzens-University of Innsbruck, Innrain 80/82, 
      6020 Innsbruck, Austria. Electronic address: Andreas.Bernkop@uibk.ac.at.
LA  - eng
PT  - Comparative Study
PT  - Journal Article
DEP - 20180601
PL  - Netherlands
TA  - Eur J Pharm Biopharm
JT  - European journal of pharmaceutics and biopharmaceutics : official journal of 
      Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V
JID - 9109778
RN  - 0 (Acrylic Resins)
RN  - 0 (Nicotinic Acids)
RN  - 0 (Sulfhydryl Compounds)
RN  - 059QF0KO0R (Water)
RN  - 4Q93RCW27E (carbopol 940)
RN  - EU7D859ABZ (2-mercaptonicotinic acid)
RN  - K848JZ4886 (Cysteine)
SB  - IM
MH  - Acrylic Resins/chemistry
MH  - Animals
MH  - Cysteine/chemistry
MH  - Drug Delivery Systems/*methods
MH  - Freeze Drying
MH  - Hydrophobic and Hydrophilic Interactions
MH  - Intestinal Mucosa/drug effects/*metabolism
MH  - Nicotinic Acids/chemistry
MH  - Particle Size
MH  - Porosity
MH  - Sulfhydryl Compounds/chemistry
MH  - Swine
MH  - Tensile Strength
MH  - Water/chemistry
OTO - NOTNLM
OT  - Anhydrous
OT  - Chain conformation
OT  - Mucoadhesion
OT  - Poly(acrylic acid)
OT  - Thiolation
EDAT- 2018/06/04 06:00
MHDA- 2018/10/26 06:00
CRDT- 2018/06/04 06:00
PHST- 2018/02/06 00:00 [received]
PHST- 2018/05/28 00:00 [revised]
PHST- 2018/05/31 00:00 [accepted]
PHST- 2018/06/04 06:00 [pubmed]
PHST- 2018/10/26 06:00 [medline]
PHST- 2018/06/04 06:00 [entrez]
AID - S0939-6411(18)30197-8 [pii]
AID - 10.1016/j.ejpb.2018.05.038 [doi]
PST - ppublish
SO  - Eur J Pharm Biopharm. 2018 Aug;129:273-281. doi: 10.1016/j.ejpb.2018.05.038. Epub 
      2018 Jun 1.