Solid lipid nanoparticle as an effective drug delivery system of a novel curcumin derivative: formulation, release in vitro and pharmacokinetics in vivo.

CONTEXT: Curcumin (Cur) has a short duration of action which limits its therapeutic efficacy. Carbonic acid 17-(1,5-dimethyl-hexyl)-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl ester 4-[7-(4-hydroxy-3-methoxy-phenyl)-3,5-dioxo-hepta-1,6-dienyl]-2-methoxy-phenyl ester (CUD), as a small molecule derivative of Cur with superior stability, has been developed in our laboratory. OBJECTIVE: CUD-loaded solid lipid nanoparticles (CUD-SLN) were prepared to prolong the duration of the drug action of Cur. MATERIALS AND METHODS: CUD-SLN were prepared with Poloxamer 188 (F68) and hydrogenated soybean phospholipids (HSPC) as carriers, and the prescription was optimized. The in vitro release of CUD and CUD-SLN was investigated. CUD-SLN (5 mg/kg) was injected into Sprague Dawley (SD) rats to investigate its pharmacokinetic behaviour. RESULTS: CUD-SLN features high entrapment efficiency (96.8 ± 0.4%), uniform particle size (113.0 ± 0.8 nm), polydispersity index (PDI) (0.177 ± 0.007) and an appropriate drug loading capacity (6.2 ± 0.1%). Optimized CUD-SLN exhibited sustained release of CUD for about 48 h. Moreover, the results of the pharmacokinetic studies showed that, compared to Cur, CUD-SLN had a considerably prolonged half-life of 14.7 h, slowed its metabolism in vivo by 35.6-fold, and had an improved area under the curve (AUC0-t) of 37.0-fold. CONCLUSIONS: CUD-SLN is a promising preparation for the development of a small molecule derivative of Cur.

Bone-targeting drug delivery system of biomineral-binding liposomes loaded with icariin enhances the treatment for osteoporosis.

BACKGROUND: Osteoporosis is a bone-incapacitating malady and it is characterized by obvious bone mass loss and bone microarchitecture deterioration. Current treatments for osteoporosis have many limitations, including the non-obvious therapeutic effect and long-term safety issues. Icariin is a pharmacologically active flavonoid glycoside, which shows potential application in treatment of osteoporosis. But its clinical application is limited by the inherent disadvantages such as poor water solubility, first pass effect after oral administration, and low bioavailability. Moreover, due to lack of targeting ability, icariin cannot accumulate at the local diseased region to provide early protection from fractures. To solve the application problems of icariin and enhance its therapeutic effects on osteoporosis, this work aimed to design a targeting drug delivery system of biomineral-binding liposomes (BBL) mediated by pyrophosphate ions. RESULTS: Biomineral-binding liposomes enhanced the binding ability of liposomes with hydroxyapatite particles. It increased the serum level of alkaline phosphatase and reduced that of tartrate-resistant acid phosphatase 5b. Meanwhile, BBL increased the mechanical strength of femoral midshaft, preserving the trabecular bone microarchitecture. Moreover, BBL could initiate bone turnover/remodeling of rats with osteoporosis. CONCLUSIONS: This drug targeting delivery system of BBL loading with icariin showed more therapeutic advantages than the free icariin for the treatment of osteoporosis, which may be a kind of valid candidate in future osteoporosis therapy.

[Mathematic modeling and experimental validation of macrostate quality expression for multicomponent in Chinese materia medica].

OBJECTIVE: To establish the unitive multicomponent quality system bridged macrostate mathematic model parameters of material quality and microstate component concentration for Chinese materia medica (CMM). METHOD: According to law of biologic laws of thermodynamics, the state functions of macrostate qulity of the CMM were established. The validation test was carried out as modeling drug as alcohol extract of Radix Rhozome (AERR), their enthalpy of combustion was determined, and entropy and the capability of information by chromatographic fingerprint were assayed, and then the biologic apparent macrostate parameters were calculated. RESULT: The biologic macrostate mathematic models, for the CMM quality controll, were established as parameters as the apparent equilibrium constant, biologic enthalpy, Gibbs free energy and biologic entropy etc. The total molarity for the 10 batchs of AERR were 0.153 4 mmol x g(-1) with 28.26% of RSD, with the average of apparent equilibrium constants, biologic enthalpy, Gibbs free energy and biologic entropy were 0.039 65, 8 005 J x mol(-1), -2.408 x 10(7) J x mol(-1) and - 8.078 x 10(4) J x K(-1) with RSD as 6.020%, 1.860%, 42.32% and 42.31%, respectively. CONCLUSION: The macrostate quality models for CMM can represent their intrinsic quality for multicomponent dynamic system such as the CMM, to manifest out as if the forest away from or tree near from to see it.

[Theoretical and experimental studies on apparent solubility parameters of multiple components for Chinese materia medica with HPLC fingerprint].

OBJECTIVE: To establish the theories and methods to determine apparent solubility paraneters of multiple components for the Chinese materia medica (CMM) with HPLC fingerprint. METHOD: The mathematical functional expresses to determine the apparent solubility parameters for multiple constituents were established according to total quantum geometrical average retention time (TQGART) for HPLC fingerprint that characterized the entirety tendencies for all-over chromatographic peaks, validated by the aloe-emodin's solubility parameters which had been determined. The HPLC for the aloe-emodin's solubility parameters were carried out with an Alltech Apollo C18 as column, Acetone: Water as mobile phase, gradient elution,flow rate as 1.0 mL x min(-1), the detection wave-length as 430 nm and the temperature as 30 degrees C. RESULT: The mathematical functional model between the TQGART of HPLC chromatographic fingerprint and the total quantum apparent solubility parameters was established and used to determine the aloe-emodin's mixture solubility parameter as 36.12 J(1/2) x cm(-3/2), nearly equal to 35.57, 36.07 J(1/2) x cm(-3/2) calculated by ration of peak area ratios and molecular fraction, respectively. CONCLUSION: The TQGART of HPLC fingerprint can be used to determine simultaneously the apparent or single intrinsic solubility parameters for total quantum or intrinsic solubility parameters for single in multiple constitute systems, by which theoretical and technologic platform to study the compatibility rule and dosage form reform of the single CMM will be established.

[Theoretical and experimental studies on solubility parameters of multiple components for traditional Chinese materia medica with HPLC].

OBJECTIVE: To establish the theories and methods to determine solubility parameters of multiple components for the traditional Chinese material medica (TCMM) with HPLC. METHOD: The mathematical expresses to determin the solubility parameters were established according to chromatographic and Hildebrand-Scatchard theories, The HPLC experiments were carried out at 40 degrees C on an Alltech Apollo C18 column (4.6 mm x 250 mm, 5 microm) eluted with acetone and water in gradient mode. The flow rate was 1.0 mL min(-1), and the detection wavelength was 254 nm. The injection volume was 1 0 microL. RESULT: The mathematical expresses between the retention time and the solubility parameters were established and used to determin caffeine solubility parameter as 28.31 J(1/2) cm(-3/2) in accordance with 28.84 J(1/2) cm(-3/2) reported by literature, and those of aloe-emodin, rhein, emodin, physcione as 39.70 J(1/2) cm(-3/2), 39.08 J(1/2) cm(-3/2), 38.37 J(1/2) cm(-3/2), 36.42 J(1/2) cm(-3/2) respectively. CONCLUSION: The retention time of HPLC can be used to determine the solubility parameters of multiple componets. The established method is useful for the compatibility rule study of traditional Chinese medicine.