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The use of nano polymeric self-assemblies based on novel amphiphilic polymers for oral hydrophobic drug delivery.
- Source :
-
Pharmaceutical research [Pharm Res] 2012 Mar; Vol. 29 (3), pp. 782-94. Date of Electronic Publication: 2011 Oct 05. - Publication Year :
- 2012
-
Abstract
- Purpose: To investigate the use of nano self-assemblies formed by polyallylamine (PAA) modified with 5 or 10% mole fluorenylmethoxy carbonyl (Fmoc(5)/(10)), dimethylamino-1-naphthalenesulfonyl (Dansyl(5)/(10)) and 5% mole cholesteryl group (Ch(5)) for oral hydrophobic drug delivery.<br />Methods: Propofol, griseofulvin and prednisolone were loaded into amphiphilic PAAs. Particle size and morphology of drug-loaded self-assemblies were determined using photon correlation spectroscopy and transmission electron microscopy. Solubilising capacity, in vitro drug release and formulation stability were analysed by HPLC, and in vitro biocompatibility studies (haemolysis and cytotoxicity) were carried out on bovine erythrocytes and Caco-2 cells, respectively. Dansyl(10) and Ch(5) griseofulvin formulations were administered intra-gastrically to rats, and drug plasma levels were analysed by HPLC.<br />Results: Drug-encapsulated self-assemblies typically have hydrodynamic size of 300-400 nm. Dansyl(10) exhibited universal drug solubiliser property and had significantly improved prednisolone, griseofulvin and propofol solubility by 145, 557 and 224-fold, respectively. Fmoc polymers resulted in modest drug solubility improvement. These polymers were non-haemolytic, did not enhance cytotoxicity compared to unmodified PAA, and demonstrated significant increase in griseofulvin plasma concentration compared to griseofulvin in water after oral administration.<br />Conclusions: Ch(5) and Dansyl(10) showed promising potential as nano-carriers for oral hydrophobic drug delivery.
- Subjects :
- Administration, Oral
Animals
Anti-Inflammatory Agents pharmacokinetics
Caco-2 Cells
Cattle
Cell Survival
Cholestenes chemistry
Cholestenes toxicity
Dansyl Compounds chemistry
Dansyl Compounds toxicity
Drug Carriers toxicity
Fluorenes chemistry
Fluorenes toxicity
Griseofulvin pharmacokinetics
Hemolysis drug effects
Humans
Hydrophobic and Hydrophilic Interactions
Hypnotics and Sedatives pharmacokinetics
Male
Polyamines toxicity
Prednisolone pharmacokinetics
Propofol pharmacokinetics
Rats
Rats, Sprague-Dawley
Anti-Inflammatory Agents administration & dosage
Drug Carriers chemistry
Griseofulvin administration & dosage
Hypnotics and Sedatives administration & dosage
Polyamines chemistry
Prednisolone administration & dosage
Propofol administration & dosage
Subjects
Details
- Language :
- English
- ISSN :
- 1573-904X
- Volume :
- 29
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Pharmaceutical research
- Publication Type :
- Academic Journal
- Accession number :
- 21971828
- Full Text :
- https://doi.org/10.1007/s11095-011-0602-7