Improving solubility and cellular absorption of Paclitaxel with solid lipid nanoparticles and cyclodextrin Jong-Suep Baek , Jae-Woo So, Ji-Sook Hwang, Cheong-Weon Cho College of Pharmacy, Chungnam National University, Daejeon 305-764, South Korea. INTRODUCTION. 3. Surface tension.
Improvingsolubility and cellular absorption of Paclitaxel with solid lipid nanoparticles and cyclodextrin
Jong-Suep Baek, Jae-Woo So, Ji-Sook Hwang, Cheong-Weon Cho
College of Pharmacy, Chungnam National University, Daejeon 305-764, South Korea.
3. Surface tension
Paclitaxel (PTX), the first of a new class of microtubule stabilizing agents, is recognized as an effective chemotherapeutic agent for a wide variety of solid tumors. Clinical application of this highly effective drug in the treatment of cancer is limited because of its poor aqueous solubility and poor oral bioavailability. Therefore, PTX-incorporated SLN, PTX-HPCD and surface-modified PTX-incorporated SLN were prepared and evaluated by the physicochemical and biopharmaceutical characterization in this study. The major peaks of PTX were disappeared in the FT-IR spectra for surface-modified PTX-incorporated SLN. The BET surface area of PTX –incorporated SLN (PS3), and surface-modified PTX-incorporated SLN (FM4) was 4.09 m2/g and 4.79 m2/g, respectively. Based on the increase of BET surface area of FM4 compared to that of PS3, FM4 showed a 20% of dissolution and the cellular uptake of 29-fold increase compared to that of PS3. Taxol formulation showed 78% of cell viability and FM4 showed 72% of cell viability with 10uM of PTX, indicating FM4 did not show the higher toxicity compared to Taxol formulation. Therefore, FM4 could be good carrier for improving solubility and cellular absorption of water insoluble drug.
* Both lecithin and poloxamer 188 samples, tension was lowest at 75mg
Fig 4. Surface tension values of SLN with different surfactant amount
4. DSC and XRD
Fig 5. DSC (A) and XRD (B)
PTX : low solubility
Fig 1. low permeability and low solubility of paclitaxel in BCS class
1. Preparation of SLN and SLN+HPCD
Stearic acid (Lipid)
10mg PTX in EtOH
Fig 6. FT-IR spectra of HPCD (A) and SLN+HPCD (B)
(A) Intensity of the PTX major peak (1730cm-1, 1250cm-1) was reduced in the case of HPCD incorporation. It was evidence of an interaction at the solid state between PTX and HPCD.
(B) Intensity of the lipid major peak (2850cm-1 , 1670cm-1) was reduced in the case of SLN+HPCD. It was evidence that lipid’s surface was surrounded by HPCD.
70℃ water bath
Sonification 15 min in 70 ℃ water bath
6. Cellular uptake study
1. Taxol and HPCD was below the LOQ (<0.015%)
2. In case of SLN, Uptake % of PTX was 0.129 (±0.046)%
3. In case of SLN+HPCD, Uptake % was 29 times higher than that of SLN
4℃ 10% mannitol
Sonification 15 min in 4 ℃ water bath
Fig 7. Caco-2 cellular uptake of each formula
7. Cytotoxicity study
RESULTS AND DISCUSSION
Table 1. Solubility of each formulation
Fig 8. Caco-2 cell cytotoxicity study of SLN+HPCD and Taxol
a) b) c)
Fig 2. Dissolution profile of PTX
Fig 9. HeLA cell cytotoxicity study of SLN and SLN+HPCD
(A) (B) (C)
Table 2. Physical characteristic
Fig 3. SEM images
of PTX (A), SLN (B), SLN+HPCD (C)