Background and Objectives: Lipid-based self-nanoemulsifying drug delivery systems (SNEDDS) have resurged the eminence of nanoemulsions by modest adjustments and offer many valuable opportunities in drug delivery. Chlorpromazine, an antipsychotic agent with poor aqueous solubility—with extensive first-pass metabolism—can be a suitable candidate for the development of SNEDDS. The current study was designed to develop triglyceride-based SNEDDS of chlorpromazine to achieve improved solubility, stability, and oral bioavailability. Materials and Methods: Fifteen SNEDDS formulations of each short, medium, and long chain, triglycerides were synthesized and characterized to achieve optimized formulation. The optimized formulation was characterized for several in vitro and in vivo parameters. Results: Particle size, zeta potential, and drug loading of the optimized SNEDDS (LCT14) were found to be 178 ± 16, −21.4, and 85.5%, respectively. Long chain triglyceride (LCT14) showed a 1.5-fold increased elimination half-life (p < 0.01), up to 6-fold increased oral bioavailability, and 1.7-fold decreased plasma clearance rate (p < 0.01) compared to a drug suspension. Conclusion: The findings suggest that SNEDDS based on long-chain triglycerides (LCT14) formulations seem to be a promising alternative for improving the oral bioavailability of chlorpromazine.

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maleylacetate reductases. NCgl1111 encoded a putative monooxygenase, but this putative hydroxylase was very different from previously functionally identified hydroxylases. Cloning and expression of NCgl1111 in E. coli revealed that NCgl1111 encoded a resorcinol hydroxylase that needs NADPH as a cofactor. E. coli cells containing Ncgl1111 and Ncgl1113 sequentially converted resorcinol into maleylacetate. NCgl1110 and NCgl2950 both encoded putative TetR family repressors, but only NCgl1110 was transcribed and functional. NCgl2953 encoded a putative transporter, but disruption of this gene did not affect resorcinol degradation by C. glutamicum. The function of NCgl2953 remains unclear.Various resorcinol compounds are produced in nature as secondary plant products (4). Early studies indicated that resorcinol was degraded via three different pathways in bacteria: In Azotobacter vinelandii, resorcinol was converted into pyrogallol, and subsequently the aromatic ring was cleaved by a pyrogallol 1,2-dioxygenase (9). Pseudomonas putida apparently adopted two different pathways: Resorcinol was converted into hydroxyquinol, and hydroxyquinol was subsequently degraded by (i) 2,3,5-trihydroxytoluene 1,2-dioxygenase (meta cleavage) (3) and (ii) hydroxyquinol 1,2-dioxygenase (ortho cleavage) (4). For all three degradative pathways, degradation of resorcinol was initiated by hydroxylation, although the hydroxylation happened at different positions of the aromatic ring: C-2 for A. vinelandii and C-4 or C-6 for P. putida. Two resorcinol hydroxylases from P. putida were purified, but they were not characterized at the genetic level (16,17). Evidence supporting the conversion of resorcinol into pyrogallol by resorcinol-induced cells of A. vinelandii was obtained, but attempts to detect resorcinol 2-hydroxylase activity failed (9). To the best of our knowledge, no amino acid sequence of any resorcinol hydroxylase has been reported.Not only is hydroxyquinol involved in resorcinol degradation; it is also the key intermediate during microbial degradation of a range of aromatic compounds, such as chlorophenol (15), 2,4,6-trichlorophenol (14), dibenzo-p-dioxin (1), 4-aminophenol (27), and 2-aminobenzoate (24). Consequently, the degradation of hydroxyquinol and its derivatives is of importance for the understanding of microbial processes that govern the metabolism of aromatic compounds and for the understanding of the geobiochemical cycling of aromatic compounds. Recently, advances have been made in the understanding of aromatic compound degradation by Corynebacterium glutamicum (7,25,26). Here we describe the genetic characterization of the resorcinol catabolic pathway in C. glutamicum. MATERIALS AND METHODSBacterial strains, plasmids, and culture conditions. Bacterial strains and plasmids used in this study are listed in Table 1. Escherichia coli was grown aerobically on a rotary shaker (150 rpm) at 37°C in Luria-Bertani (LB) broth or on an LB plate with 1.5% (wt/vol) agar. C. glutamicum was routinely grown at 30°C in LB or in mineral s...