Preparation of PEGylated Liposomal Ginsenoside;Formulation Design and in vitro Evaluation

Abstract

Cui et al.: Ginsenoside Rg3-loaded PEGylated liposomesIn this study, ginsenoside Rg3-loaded PEGylated liposomes were prepared and optimized using the Box-Behnken design. These liposomes were characterized, the cumulative release profiles were investigated and compared with ginsenoside Rg 3 -loaded liposomes in vitro. To improve the stability ginsenoside Rg3-loaded PEGylated liposomes were freeze-dried and the lyoprotectants to be added were screened. The results showed that the liposomes have a small particle size (152.58±0.74 nm) and spherical shape. The encapsulation efficiency and drug-loading rate were approximately 85.24±1.02 and 7.44±0.08 %, respectively. For lyoprotectants, 2 % lactose was chosen as the lyophilized protectant according to the appearance, re-dispersity, particle size, and entrapment efficiency of lyophilization of ginsenoside Rg3loaded PEGylated liposomes. In vitro release showed that ginsenoside Rg3-loaded PEGylated liposomes showed a more obvious sustained release effect, which suggests that ginsenoside Rg3-loaded PEGylated liposomes might enhance the therapeutic effect of ginsenoside Rg3.

Ginsenosides emerging as both bifunctional drugs and nanocarriers for enhanced antitumor therapies

“…Growth rate of BALB/c nude mice inoculated with A549 tumor cells was significantly inhibited by L-Rg3. Besides, Tumor growth can be inhibited by liposome by reducing MVD and enhancing angiogenesis inhibition [ 97 ] DSPE-PEG2000 Rg3 NA NA 7.44% ± 0.08% 85.24% ± 1.02% In vitro : Rg3-PEGylated liposomes showed sustained release [ 96 ] DSPE-PEG2000 Rh2 NA A549 cells/mice 15.3% 88.2% In vitro : IC 50 values of A549 cells treated with DLT indicated that tumor growth could be inhibited by DLT In vivo : DLT showed stronger antiproliferation and apoptosis effects on xenografted tumors. DDS was safer than cisplatin in treatment of tumors [ 98 ] mPEG-PLA Rh2 Passive tumor targeting HepG2/mice NA 94.93% ± 4.18% In vivo : Fluorescence intensity at tumor site decreased gradually after injection of PLP for 8 h and lasted for 24 h. Rh2-PLP was superior to Rh2-LP and Rh2-CLP in anti-tumor effect [ 100 ] EYPC/Rh2 /Rg3/Rg5 PTX/Rh2/Rg3 /Rg5 Active targeting: Rh2/Rg3/Rg5 BGC-823 cells/mice Rh2: 5.6% ± 0.3% Rg3: 7.3% ± 0.4% Rg5: 4% ± 0.1% Rh2: 91.3% ± 2.1% Rg3: 95.5% ± 3.3% Rg5: 82.8% ± 1.6% In vitro : Ginsenoside liposome can be accumulated in tumor for recognizing GLUT carrier on tumor cell membrane In vivo : Ginsenosides showed significant synergistic effects with PTX for antitumor activity [ 26 ] EYPC/Rh2 PTX/Rh2 Active targeting: Rh2 4T1 cells /mice 5.6% …”

“…It has been demonstrated that PEGylated liposomes loading ginsenoside Rg3 display sustained-release and enhanced therapeutic effects with longer blood circulation time and enhanced drug uptake [ 96 , 97 ]. In particular, the growth rate of BALB/c nude mice inoculated with A549 tumor cells was inhibited significantly by L-Rg3 after intravenous injection of the drug, which subdued the tumor growth through reducing microvessel density (MVD) and enhancing angiogenesis inhibition [ 97 ].…”

“…PEG is the most widely used nonionic hydrophilic polymer with solubilization and stealth properties [ 170 ]. In addition, ligands including PEG, CS, amphiphilic compounds, peptides and proteins can reduce the tendency of particle aggregation through spatial stability, thus exhibiting higher stability in storage and application [ 88 , 90 , 96 , 101 , 118 ].…”

Micron and nano hybrid ufasomes from conjugated linoleic acid, their vesiculation and encapsulation of ginsenoside Rg3

“…27 The most applied stratagem to overcome the solubility issue is encapsulation, which can improve oral bioavailability, significantly prolong pharmacodynamics and reduce drug toxicity. 25,[28][29][30] The wall material for the encapsulation could be polymer, 29,[31][32][33] or small molecules like cholesterol accompanied with polyethylene glycol (PEG), that has been questioned due to various disadvantages, 31 while the popular capsules could be liposomes, 5,31,[34][35][36] gel 37 and micelle. 38,39 In our early work, nano-vesicles of conjugated linoleic acid (CLA) were prepared with different surfactants and widened pH window of vesiculation.…”

“…Its clinical application is limited due to its poor water solubility, short circulating half‐life and poor specificity for tumor tissue targeting 27 . The most applied stratagem to overcome the solubility issue is encapsulation, which can improve oral bioavailability, significantly prolong pharmacodynamics and reduce drug toxicity 25,28‐30 . The wall material for the encapsulation could be polymer, 29,31‐33 or small molecules like cholesterol accompanied with polyethylene glycol (PEG), that has been questioned due to various disadvantages, 31 while the popular capsules could be liposomes, 5,31,34‐36 gel 37 and micelle 38,39 …”