ABSTRACT
The therapeutic application of artemisinin (ART) is restricted in application due to its poor water solubility and stability. In this study, the long-circulating liposomes (L-Lip) were constructed to improve the solubility and stability of ART. The preparation method, physicochemical properties, serum stability, in vitro release profile and cytotoxicity of the ART loaded long-circulating liposomes were investigated. Using the particle size and entrapment efficiency (EE) as the evaluation index, the preparation procedure was optimized by the Box-Behnken response surface design based on the single factor screening method. The ART loaded long-circulating liposomes were prepared by filming rehydration method, and evaluated with particle size and entrapment efficiency. The optimal formulation was as follows:lipid-cholesterol=5.22:1 (mass ratio), drug-lipid=1:23.15 (mass ratio), lipid concentration=14.35 mg·mL-1, and molar percentage of mPEG=2%. The morphology of L-Lip was uniformly spherical shape according to optimal formulation. The mean size and polydispersity index (PDI) were about (113.3 ±4.7) nm and 0.227 ±0.022 respectively, the zeta potential was (-12.9 ±2.6) mV, and the entrapment efficiency (EE) of ART was (95.88 ±4.8)%. The L-Lip had good stability at 4℃ for 15 days and the particle sizes did not exhibit significant variations in 50% rat plasma over 24 h at 37℃. The in vitro release study of formulation showed a sustained release. Moreover, the cytotoxicity exhibited that blank liposomes were of great safety. Compared with the free ART, the liposome formulation achieved lower cytotoxicity at the high concentration. The L-Lip successfully prepared by a simple filming-rehydration method exhibited ideal physicochemical properties and were enhanced safety, which may sever as a promising nanoplatform for clinical application.
ABSTRACT
The therapeutic application of deoxypodophyllotoxin (DPT) is limited due to its poor water solubility and stability. In the present study, the micelles assembled by the amphiphilic block copolymers (mPEG-PDLLA) were constructed to improve the solubility and safety of DPT for their in vitro and in vivo application. The central composite design was utilized to develop the optimal formulation composed of 1221.41 mg mPEG-PDLLA, the weight ratio of 1 : 4 (mPEG-PDLLA : DPT), 30 mL hydration volume and the hydration temperature at 40 °C. The results showed that the micelles exhibited uniformly spherical shape with the diameter of 20 nm. The drug-loading and entrapment efficiency of deoxypodophyllotoxin-polymeric micelles (DPT-PM) were about (20 ± 2.84)% and (98 ± 0.79)%, respectively, indicating that the mathematical models predicted well for the results. Compared to the free DPT, the cytotoxicity showed that blank micelles possessed great safety for Hela cells. In addition, the DPT loaded micelle formulation achieved stronger cytotoxicity at the concentration of 1 × 10 mol·L, which showed significant difference from free DPT (P < 0.05). In conclusion, the micelles were highly promising nano-carriers for the anti-tumor therapy with DPT.
Subject(s)
Humans , Antineoplastic Agents , Chemistry , Toxicity , Cell Survival , Drug Carriers , Chemistry , Drug Delivery Systems , Methods , Drug Design , HeLa Cells , Micelles , Particle Size , Podophyllotoxin , Chemistry , Toxicity , Polyesters , Chemistry , Polyethylene Glycols , Chemistry , Solubility , Surface PropertiesABSTRACT
The therapeutic application of deoxypodophyllotoxin (DPT) is limited due to its poor water solubility and stability. In the present study, the micelles assembled by the amphiphilic block copolymers (mPEG-PDLLA) were constructed to improve the solubility and safety of DPT for their in vitro and in vivo application. The central composite design was utilized to develop the optimal formulation composed of 1221.41 mg mPEG-PDLLA, the weight ratio of 1 : 4 (mPEG-PDLLA : DPT), 30 mL hydration volume and the hydration temperature at 40 °C. The results showed that the micelles exhibited uniformly spherical shape with the diameter of 20 nm. The drug-loading and entrapment efficiency of deoxypodophyllotoxin-polymeric micelles (DPT-PM) were about (20 ± 2.84)% and (98 ± 0.79)%, respectively, indicating that the mathematical models predicted well for the results. Compared to the free DPT, the cytotoxicity showed that blank micelles possessed great safety for Hela cells. In addition, the DPT loaded micelle formulation achieved stronger cytotoxicity at the concentration of 1 × 10 mol·L, which showed significant difference from free DPT (P < 0.05). In conclusion, the micelles were highly promising nano-carriers for the anti-tumor therapy with DPT.