title: Drug distribution in nanostructured lipid particles.
abstract: The targeted design of nanoparticles for efficient drug loading and defined release profiles is even after 25years of research on lipid-based nanoparticles still no routine procedure. It requires detailed knowledge about the interaction of the drug with the lipid compounds and about its localisation and distribution in the nanoparticle. We present here an investigation on nano-sized lipid particles (NLP) composed of Gelucire and Witepsol as solid lipids, and Capryol as liquid lipid, loaded with Dexamethasone, a glucocorticoid used in topical treatment of inflammatory dermal diseases. The interactions of Dexamethasone, which was spin-labelled by 3-(Carboxy)-2,2,5,5-tetramethyl-1-pyrrolidinyloxy (DxPCA), with its microenvironment are monitored by EPR spectroscopy at 94GHz at low temperatures. The mobility of the spin-labelled drug was probed by X-band EPR at room temperature. In order to relate the magnetic and dynamic parameters deduced from EPR to the local environment of the spin probe in the NLP, investigations of DxPCA in the individual lipid compounds were carried out. The magnetic parameters reflecting the polarity of DxPCA's environment as well as the parameters describing the mobility of the drug reveal that in the case of colloidal dispersions of the lipids and also the NLP DxPCA is attached to the surface of the nanoparticles. Although the lipophilic drug is almost exclusively associated with the NLP in aqueous solution, dilution experiments show, that it can be easily released from the nanoparticle.
authors: Berlin Joint EPR Lab, Freie Universität Berlin, Fachbereich Physik, Berlin, Germany.
authors: Siavash
authors: S
authors: Saeidpour
authors: Department of Dermatology, Venerology and Allergology, Center of Experimental and Applied Cutaneous Physiology, Charité - Universitätsmedizin Berlin, Germany.
authors: Silke B
authors: SB
authors: Lohan
authors: Freie Universität Berlin, College of Pharmacy, Berlin, Germany.
authors: Agnieszka
authors: A
authors: Solik
authors: Department of Dermatology, Venerology and Allergology, Center of Experimental and Applied Cutaneous Physiology, Charité - Universitätsmedizin Berlin, Germany.
authors: Victoria
authors: V
authors: Paul
authors: Freie Universität Berlin, College of Pharmacy, Berlin, Germany.
authors: Roland
authors: R
authors: Bodmeier
authors: Freie Universität Berlin, College of Pharmacy, Berlin, Germany.
authors: Gaith
authors: G
authors: Zoubari
authors: Freie Universität Berlin, Institut für Chemie und Biochemie, Berlin, Germany.
authors: Michael
authors: M
authors: Unbehauen
authors: Freie Universität Berlin, Institut für Chemie und Biochemie, Berlin, Germany.
authors: Rainer
authors: R
authors: Haag
authors: Berlin Joint EPR Lab, Freie Universität Berlin, Fachbereich Physik, Berlin, Germany.
authors: Robert
authors: R
authors: Bittl
authors: Department of Dermatology, Venerology and Allergology, Center of Experimental and Applied Cutaneous Physiology, Charité - Universitätsmedizin Berlin, Germany.
authors: Martina C
authors: MC
authors: Meinke
authors: Berlin Joint EPR Lab, Freie Universität Berlin, Fachbereich Physik, Berlin, Germany. Electronic address: christian.teutloff@fu-berlin.de.
authors: Christian
authors: C
authors: Teutloff
mesh_terms: D003080:Cold Temperature; D003102:Colloids / Q000737:chemistry; D003907:Dexamethasone / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D015195:Drug Design; D004578:Electron Spin Resonance Spectroscopy; D005223:Fats / Q000737:chemistry; D005938:Glucocorticoids / Q000737:chemistry; D008055:Lipids / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry*; D009821:Oils / Q000737:chemistry; D010316:Particle Size; D011108:Polymers / Q000737:chemistry; D011409:Propylene Glycols / Q000737:chemistry; D012995:Solubility; D013113:Spin Labels; D013499:Surface Properties; D014280:Triglycerides / Q000737:chemistry
chemical_list: D003102:Colloids; D004337:Drug Carriers; D005223:Fats; D005938:Glucocorticoids; D008055:Lipids; D009821:Oils; D011108:Polymers; D011409:Propylene Glycols; D013113:Spin Labels; D014280:Triglycerides; C584816:capryol propylene glycol monocaprylate; C071184:Gelucire 50-13; C009683:witepsol; D003907:Dexamethasone
keywords: 3-(Carboxy)-2,2,5,5-tetramethyl-1-pyrrolidinyloxy (PubChem CID: 519874); Dermal drug delivery; Dexamethasone; Dexamethasone (PubChem CID: 5743); Drug delivery system; Electron paramagnetic resonance (EPR) spectroscopy; Lipids; Nanoparticles; Propylene glycol monocaprylate (Capryol® 90) (PubChem CID: 53630264); Spinlabel; Stearoyl macrogolglycerides (Gelucire® 50/13) (PubChem SID: 135354605); Witepsol (ChemIDplus: 0091744422)