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Inflammatory bowel disease (IBD) is a common disease characterized by chronic inflammation in gastrointestinal tracts, which is primarily treated by administering anti-inflammatory and immunosuppressive drugs that inhibit the burden of intestinal inflammation and improve disease-related symptoms. However, the established therapeutic strategy has limited therapeutic efficacy and adverse drug reactions. Therefore, new disease-targeting drug-delivery strategies to develop more effective treatments are urgent. This review provides an overview of the drug-targeting strategies that can be used to treat IBD, and our recent attempts on the colon-specific delivery system (Pae-SME-CSC) with a paeonol-loaded self-microemulsion (Pae-SMEDDS) are introduced.

20(S)-Protopanaxadiol (20(S)-PPD)is one type of sapogenin of protopanaxadiols and has a variety of pharmacological activities. In order to improve the dissolution of 20(S)-PPD as well as its oral bioavailability, a self-microemulsifying drug delivery system (SMEDDS) was utilized for 20(S)-PPD preparation. Following the preparation of the 20(S)-PPD SMEDDS, its dissolution, stability, and intestinal absorption in rats were studied, and the pharmacokinetics and optimal dosage after oral administration were evaluated. The dissolution tendency of the SMEDDS in phosphate buffered saline (PBS), 0.1 M HCl and distilled water was consistent. SMEDDS was stable under a condition of high temperature (40°C), high humidity or with strong light irradiation, or within 6 h in artificial digestive tracts. 20(S)-PPD SMEDDS was well-absorbed in all intestinal segments in rats. When the drug concentration was higher than 200 µg/mL or the perfusion flow was faster than 0.5 mL/min, passive diffusion of drug in the duodenum reached a saturated level. In addition, Pglycoprotein inhibitor did not affect the intestinal absorption of 20(S)-PPD SMEDDS. Pharmacokinetic study showed that T max in male rats was shortened significantly, while C max and area under the curve (AUC (0-t) ) were remarkably increased. The relative oral bioavailability of 20(S)-PPD SMEDDS was increased approximately three fold compared with the 20(S)-PPD carboxy methyl cellulose (CMC). 20(S)-PPD SMEDDS (100 mg/mL) was administered by gastric infusion to both mice and rats for 14 d. SMEDDS improved the oral bioavailability of 20(S)-PPD and reduced the necessary drug dosage. 20(S)-PPD SMEDDS could become a promising clinical alternative as an anti-tumor or antidepressant drug.Key words 20(S)-protopanaxadiol; self-microemulsifying drug delivery system; preparation; bioavailability; intestinal absorption; pharmacokinetics Panax ginseng is documented to tonify internal organs, benefit the spirit, suppress the fright as well as improve eyesight and intelligence.1) The long term application also facilitates relaxation and increases life span.2) Various chemical components were distinguished in Panax ginseng, including saponins, volatile oil, polysaccharides, amino acid and polypeptide, and microelements, of which ginsenosides are the main active ingredients, including oleanolic acid (OA), protopanaxadiol (PPD) and protopanaxatriol type (PPT).3) 20(S)-PPD ( Fig. 1) is one of aglycones of ginsenosides and has a wide range of pharmacological activities, especially in antitumor and neurological function recovery. [4][5][6][7][8] However, the low bioavailability of ginsenosides (1% for Rb 1 , 3.4% for Rb 2 , 1.9% for Rg 1 ) after oral administration restricts their clinical applications. 9-11)Importantly, PPD is the final active component after the absorption of ginsenosides in intestine. 12,13)

Paeonol, as the main phenolic compound isolated from the Chinese herbs, has been confirmed to present anti-inflammatory effects on ulcerative colitis (UC) in our previous study. However, its poor solubility has hindered its development of being a favourable pharmaceutical product in treating colon diseases. In this study, we prepared the colon-specific delivery system (Pae-SME-CSC) with paeonol-loaded self-microemulsion (Pae-SMEDDS), and evaluated its in vitro and in vivo properties, especially the anti-inflammatory effects on UC rats. The anti-inflammatory effects were evaluated by the disease activity index, colon weight/length ratio, and macroscopic damage and microscopic damage scores. IL-17, IL-6, and TGF-β1 levels were also determined by enzyme-linked immunosorbent assay. The results showed that Pae-SME-CSC had good colon-targeting property in vivo and in vitro, with favourable stability. Efficacy evaluation showed that the dose of the paeonol group (100 mg/kg) exhibited no significant effect on UC (p > .05, compared with the model group), while the Pae-SME-CSC group (100 mg/kg) showed better anti-UC effects (p < .01 or p < .05), and its anti-inflammatory effect was close to that of the paeonol group (200 mg/kg) (p > .05). These results indicated that the developed Pae-SME-CSC was suitable for colon-specific drug delivery.

This study aims to develop a gastroretentive sustained-release drug delivery system of paeonol using floating properties and to investigate its therapeutic effects in rat models. The gastric retention tablets of paeonol (GRT-Ps) were prepared by a direct compression method, and the Box-Behnken design was used to optimize its formulation. The optimized formulation containing 15% NaHCO 3 and a 2 : 1 ratio of paeonol and HPMC-K4M floated within 1 min and remained afloat for more than 8 h in the simulated gastric fluid (200 mL, pH 1.2) and simultaneously showed the desired sustained drug release. Moreover, small tablets (3 mm) were prepared according to the same formulation and the process technology of big tablets (8 mm). A similar drug release behavior was observed between two kinds of tablets ( f 2 52), and then the evaluations of efficacy and retention capacity in vivo were conducted with small tablets. In vivo retention studies showed that the T max (2 h) of GRT-P in rat stomachs was significantly extended compared with the T max (0.5 h) of normal reference preparation. Compared with the model group, low and high doses of GRT-P could significantly inhibit the increase of malondialdehyde (MDA) in serum. Studies showed that the higher MDA content in inflammation tissue increases the inflammatory response. The ulcer inhibition rates of GRT-P in the highdose group were 59.0 and 64.1% in the ranitidine group. Results indicated that GRT-Ps had the potential for a sustained drug release and an enhanced gastric residence time with relatively high drug concentrations in the tissue distribution.Key words paeonol; gastric retention tablet; sustained release; gastric ulcer; efficacy Paeonol, also called peony phenol, is the active component of a traditional Chinese medicine, namely, moutan cortex (Paeonia suffruticosa ANDREWS, Ranunculaceae).1) Paeonol has been extensively studied for its anti-inflammatory, antioxidant, anti-atherosclerosis, anti-diabetic, and anti-mutagenic effects.2,3) However, paeonol has significant growth-inhibitory and apoptosis-inducing effects in gastric cancer cells in vitro and in vivo.4) Moreover, studies have shown that paeonol prevents inflammatory diseases of the alimentary canal, such as irritable gastric ulcer, with minimal side effects.5) However, studies on the ethanol-induced gastric ulcer effect of paeonol are lacking. Currently, the listed paeonol dosages are administered via ordinary oral tablets and injection. However, paeonol has poor water solubility, easy oxidation, and a short biological half-life. [6][7][8] The paeonol products are unable to prolong effective drug concentration in blood to influence the oral bioavailability of a drug. Therefore, the present study, which is based on the properties of paeonol, has been designed to develop gastric retention tablets using modern technology to achieve prolonged presence in the stomach, thereby improving treatment of gastric ulcer. This approach has a profound clinical significance in developing a novel sustained-release delivery syst...