Effect of Phospholipid-Based Formulations of Boswellia serrata Extract on the Solubility, Permeability, and Absorption of the Individual Boswellic Acid Constituents Present

Abstract

Boswellia serrata gum resin extracts are used widely for the treatment of inflammatory diseases. However, very low concentrations in the plasma and brain were observed for the boswellic acids (1-6, the active constituents of B. serrata). The present study investigated the effect of phospholipids alone and in combination with common co-surfactants (e.g., Tween 80, vitamin E-TPGS, pluronic f127) on the solubility of 1-6 in physiologically relevant media and on the permeability in the Caco-2 cell model. Because of the high lipophilicity of 1-6, the permeability experiments were adapted to physiological conditions using modified fasted state simulated intestinal fluid as apical (donor) medium and 4% bovine serum albumin in the basolateral (receiver) compartment. A formulation composed of extract/phospholipid/pluronic f127 (1:1:1 w/w/w) increased the solubility of 1-6 up to 54 times compared with the nonformulated extract and exhibited the highest mass net flux in the permeability tests. The oral administration of this formulation to rats (240 mg/kg) resulted in 26 and 14 times higher plasma levels for 11-keto-β-boswellic acid (1) and acetyl-11-keto-β-boswellic acid (2), respectively. In the brain, five times higher levels for 2 compared to the nonformulated extract were determined 8 h after oral administration.

Triterpenoid resinous metabolites from the genus Boswellia: pharmacological activities and potential species-identifying properties

“…Several pilot clinical trials suggest promising beneficial therapeutic effects with no serious, long-term, or irreversible adverse effects [114] but some minor adverse effects such as diarrhoea, abdominal pain and nausea [115,116]. A study deals with the evaluation and assessment of the safety/toxic potential of B. serrata indicated that B. serrata is relatively safe in rat up to the dose of 500 mg/kg B.wt [117].…”

“…However, a major limitation is the low systemic absorption in rodents and humans of BAs, especially of the major active compounds (1–4) (16–17), which have been evidenced by pharmacokinetic studies [120,121]. For example, the plasma and brain concentrations of BAs were found to be very low following oral administration of even high B. serrata doses [114]. In general, AKβ-BA (4) was not detected at all [38] while β-BA (1) and Aβ-BA (2) achieved pharmacologically relevant concentrations in plasma [114].…”

“…For example, the plasma and brain concentrations of BAs were found to be very low following oral administration of even high B. serrata doses [114]. In general, AKβ-BA (4) was not detected at all [38] while β-BA (1) and Aβ-BA (2) achieved pharmacologically relevant concentrations in plasma [114]. Besides, a permeability study on the intestinal absorption revealed poor permeability (<1 × 10 −6 cm/s) of AKβ-BA (4) [120] and moderate absorption of Kβ-BA (3) with a P app value of 1.69 × 10 −6 cm/s in the Caco-2 model [122].…”

“…For better prediction of the absorption in vivo , the permeability experiments should be more adapted to physiological conditions of the gastrointestinal tract by the addition of 4% bovine serum albumin to the receiver side [120,125], and using modified fasted state simulated intestinal fluid as apical (donor) medium [114]. Under these conditions the four BAs lacking the 11-keto moiety (β-BA (1), Aβ-BA (2), Kβ-BA (3) and AKβ-BA (4)) showed moderate permeability with P app -values between 1 and 10 × 10 −6 cm/s [120], suggesting moderate absorption (20–70%) according to Yee [126].…”

Enhanced absorption of boswellic acids by a lecithin delivery form (Phytosome®) of Boswellia extract

“…the one used in this study, in a 1:1:1 (w/w/w) formulation of BE:lecithin:pluronic f127 (co-surfactant) mixed at a 1:1 ratio with microcrystalline cellulose [20]. When compared to Casperome™ on equimolar basis, this formulation led to roughly 1.5-fold higher mean plasma levels for KBA, AKBA and βBA, as well as higher mean brain levels for βBA (roughly 10-fold).…”