Quaternary ammonium palmitoyl glycol chitosan--a new polysoap for drug delivery.
A new polysoap, quaternary ammonium palmitoyl glycol chitosan (GCPQ, M(w)=178,000 g mole(-1)) with drug solubilising potential has been synthesised and characterised. In solution hydrophobic domains of GCPQ polymeric micelles were identified by the hypsochromic shift in the lambda(max) of methyl orange and by the increase in the ratio of the fluorescence emission intensity of the third and first pyrene vibronic peaks (I(3)/I(1)). At high aqueous concentrations (>10 mg ml(-1)) GCPQ presents as a gel which solubilises pyrene (2.5 mM, normal solubility in water approximately 2 microM) on probe sonication. Dilution of the gel to a liquid solution of polymeric micelles (< or =3.75 mg ml(-1) of GCPQ), results in the observation of fluorescent pyrene excimers (excited dimers) and a high excimer to monomer fluorescence ratio (I(E)/I(M)). However, attempts to solubilise pyrene at a concentration of 2.5 mM in a liquid solution of GCPQ (3.75 mg ml(-1)) results in a reduced I(E)/I(M) value and pyrene precipitation. Viscometry measurements show a more compact conformation for the polymer solubilising pyrene than the polymer alone. The polymer is non-haemolytic when present as the liquid solution and relatively non cytotoxic. In conclusion, a new biocompatible polysoap (potential drug solubiliser) is described which forms hydrophobic domains in solution and shows hysteresis in its solubilisation of pyrene.
Uchegbu
I F
IF
Department of Pharmaceutical Sciences, Strathclyde Institute for Biological Sciences Building, University of Strathclyde, 27 Taylor Street, Glasgow G4 ONR, Scotland, UK. i.f.uchegbu@strath.ac.uk
Sadiq
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L
Arastoo
M
M
Gray
A I
AI
Wang
W
W
Waigh
R D
RD
Schätzlein
A G
AG
Schätzleinä
A G
AG
D001391:Azo Compounds / Q000378:metabolism; D002460:Cell Line; D002686:Chitin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D048271:Chitosan; D016503:Drug Delivery Systems; D005456:Fluorescent Dyes / Q000378:metabolism; D007202:Indicators and Reagents / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D015394:Molecular Structure; D008970:Molecular Weight; D011721:Pyrenes / Q000378:metabolism; D000644:Quaternary Ammonium Compounds / Q000737:chemistry*; D013050:Spectrometry, Fluorescence
D001391:Azo Compounds; D005456:Fluorescent Dyes; D007202:Indicators and Reagents; D011721:Pyrenes; D000644:Quaternary Ammonium Compounds; C114305:palmitoyl glycol chitosan; D002686:Chitin; C100258:methyl orange; D048271:Chitosan; C030984:pyrene