Encapsulation Efficiency Of Paclitaxel Research Articles

Polymer hydrophobicity regulates paclitaxel distribution in microspheres, release profile and cytotoxicity in vitro

Water-insoluble drugs such as paclitaxel (PTX) face a huge challenge for clinical applications due to their low aqueous solubility. In this study, uniform-sized poly (DL-lactic acid) (PLA), poly(DL-lactic-co-glycolic acid) (PLGA) and poly( ethylene glycol-co-lactide add) (PELA) microspheres containing PTX were prepared by premix membrane emulsification technique integrated with solvent evaporation method. The different hydrophobicity of polymer led to different distribution and crystal morphology of PTX in microspheres, which further resulted in different loading and encapsulation efficiency, release profile in vitro and cytotoxicity. The PLGA microspheres showed the highest loading and encapsulation efficiency of PTX (5.15%, 70.46%), followed by PLA microspheres (4.33%, 6433%), together with PELA microspheres (3.35%, 56.68%). The results of PTX release profile in vitro suggested that PLGA and PELA microspheres achieved a more rapid release rate than PLA microspheres due to their hydrophilic property. The antitumor activity in vitro was also evaluated by Lewis Lung Cells (LLC). The PTX-PLGA microspheres exhibited excellent antitumor activity compared with PLA and PELA microspheres, even much better than Taxol. Therefore, the PLGA microspheres show great potential in application as delivery carriers for water-insoluble drugs, PTX and others. (C) 2015 Elsevier B.V. All rights reserved.

Immunotherapeutic vitamin E nanoemulsion synergies the antiproliferative activity of paclitaxel in breast cancer cells via modulating Th1 and Th2 immune response

Paclitaxel (PTX) is used as first line treatment for metastatic breast cancer but the relief comes at a heavy cost in terms of accompanying adverse effects. The pharmaceutical credentials of PTX are further dampened by the intrinsically low aqueous solubility. In order to sideline such insidious tendencies, PTX was incorporated in a vitamin E nanoemulsion using high pressure homogenization. The encapsulation efficiency of PTX in nanoemulsion was 97.81±2.7% and a sustained drug release profile was obtained. PTX loaded nanoemulsion exhibited higher cytotoxicity in breast cancer cell line (MCF-7) when compared to free PTX and marketed formulation (Taxol). Cell cycle arrest study depicted that MCF-7 cells treated with PTX loaded nanoemulsion showed high arrest in G2-M phase. Moreover blank nanoemulsion induced additional apoptosis in breast cancer cells through G1-S arrest by disrupting mitochondrial membrane potential. Cytokine estimation study in macrophages showed that both PTX loaded nanoemulsion and blank nanoemulsion enhanced secretion of IL-12 and downregulated secretion of IL-4 and IL-10. Results suggest that inclusion of vitamin E in nanoemulsion opened multiple complementary molecular effects which not only magnified the principle antiproliferative activity of PTX but also independently showcased potential in restoring the proactive nature of the breast cancer slackened chronic immune response. In-vivo anticancer activity showed significantly improved efficacy of PTX loaded nanoemlsion compare to Taxol and free PTX. The list of plausible advantages of PTX nanoemulsification was further substantiated by acceptable haemolytic potential, reduced in-vivo toxicity and conveniently modified pharmacokinetic profile in which the AUC and MRT were extended considerably. Overall, there were strong evidences that developed formulation can serve as a viable alternative to currently available PTX options.

Synthesis and evaluation of star-shaped poly(ϵ-caprolactone)-poly(2-hydroxyethyl methacrylate) as potential anticancer drug delivery carriers

Novel star-shaped poly(ϵ-caprolactone)-b-poly(2-hydroxyethyl methacrylate) (sPCL-b-PHEMA) with 3 arm and 6 arm was synthesized by a combination of ring-opening polymerization and atom transfer radical polymerization. The structure of copolymers was confirmed by nuclear magnetic resonance (1H and 13C NMR) and Fourier transform infrared spectroscopy. The thermal behavior was measured by differential scanning calorimetry. The results showed that Tc, Tm, and Xc of the sPCL-b-PHEMA were reduced along with the increase in the length of the PHEMA block. The copolymers could self-assemble into dispersed micelles with quite low (×10−4 mg/mL) critical micelle concentration. The size and morphology of the micelles were characterized by dynamic light scattering and HAADF scanning transmission electron microscopy. It was found that the micelles were around 20–70 nm with a regular spherical shape. Moreover, drug loading content and encapsulation efficiency of paclitaxel by 3sPCL-b-PHEMA micelles were much lower than the values of 6sPCL-b-PHEMA micelles. The drug release experiments demonstrated that paclitaxelrelease was two-phase release profile and relative to the structure of sPCL-b-PHEMA.The in vitro cytotoxicity of sPCL-b-PHEMA micelles was evaluated using methylthiazoletetrazolium assay. The results showed no apparent inhibition effect on the Hela cells. These preliminary studies suggest that sPCL-b-PHEMA has a possible application as anticancer drug delivery carriers.

Release of paclitaxel from pH sensitive and biodegradable dextran based hydrogels

Two different dextran based pH sensitive and enzyme degradable hydrogels: dextran maleic acid (Dex-MA), and glycidyl methacrylated dextran (Dex-GMA) were synthesized for oral delivery of nanoparticles. Poorly water soluble drug paclitaxel nanoparticles (PAX NPs) were prepared as the model, and encapsulation efficiency of paclitaxel in the nanoparticles was optimized to 43%. The prepared hydrogels were stable in simulated gastric fluid, but were prone to swelling and degradation in the presence or absence of enzyme dextranase in simulated intestinal fluid. Release profiles of nanoparticles could be tuned from 5.5 h to as long as 24 h under simulated human GI conditions. The release of PAX NPs (110 ± 10 nm) was completed with longer time (45 h–120 h). Two possible release mechanisms were discussed for Dex-MA and Dex-GMA-co-AA hydrogels respectively: degradation controlled, and diffusion controlled. These two biodegradable hydrogels, which can release nanoparticles depending on pH changes, may be suitable as potential colon targeting vehicles for oral delivery of drug nanoparticles.

Design and Evaluation of Peptide Amphiphiles with Different Hydrophobic Blocks for Simultaneous Delivery of Drugs and Genes

In this study, peptides with six different compositions were designed and synthesized to study the effect of the structure of the hydrophobic block in triblock oligopeptide amphiphiles ((A(m) X)(n) H(5) K(15) ) on self-assembly properties, drug loading capacity and gene expression efficiency. The peptides were synthesized using a standard Fmoc-solid phase peptide synthesis protocol, which are A(12) H(5) K(15) , A(11) FH(5) K(15) , (A(5) F)(2) H(5) K(15) , (A(3) F)(3) H(5) K(15) , (AF)(6) H(5) K(15) and (AL)(6) H(5) K(15) . A(12) H(5) K(15) , A(11) FH(5) K(15) , (A(5) F)(2) H(5) K(15) and (A(3) F)(3) H(5) K(15) , formed micelles at concentrations above 200 mg · L(-1) with large size or aggregation. However, (AF)(6) H(5) K(15) and (AL)(6) H(5) K(15) had CMC values of 42 and 49 mg · L(-1) respectively, and the resulting micelles were much smaller in size as compared to the other peptide designs (108 and 233 nm for (AF)(6) H(5) K(15) and (AL)(6) H(5) K(15) , respectively). In addition, both peptides were able to load paclitaxel (PTX) into nanoparticles although PTX-loaded (AF)(6) H(5) K(15) nanoparticles had a smaller size (278 versus 295 nm, respectively). Encapsulation efficiency of PTX with (AF)(6) H(5) K(15) nanoparticles was 74%. Gene transfection studies showed that luciferase expression level induced by (AF)(6) H(5) K(15) micelles in HepG2 cell line was much higher than that mediated by (AL)(6) H(5) K(15) micelles at their respective optimal N/P ratios (3.2 × 10(8) versus 3.9 × 10(7) RLU · mg proteins(-1) ). Therefore, simultaneous delivery of PTX and luciferase-encoding plasmid was conducted using (AF)(6) H(5) K(15) micelles against HepG2 cells, and the results demonstrated that the co-delivery of PTX at 0.01 mg · L(-1) further increased luciferase expression level from 3.2 × 10(8) to 8.0 × 10(8) RLU · mg proteins(-1) at the optimal N/P ratio (i.e., 18). In summary, it is important to optimize the hydrophobic block of the oligopeptide amphiphiles in order to achieve desired properties for co-delivery of drugs and genes.

Formulation and characterization of Paclitaxel, 5-FU and Paclitaxel + 5-FU microspheres

The purpose of this study was to compare the combination (Paclitaxel+5-FU microspheres) with a single drug chemotherapy (Paclitaxel and 5-FU microspheres) against metastatic breast cancer cell line (MDA-MB 435 S). The physicochemical characteristics of the microspheres (i.e. encapsulation efficiency, particle size distribution, in vitro release, thermal characteristics) were studied. The results demonstrated that the encapsulation efficiency of Paclitaxel was high (90%) when the drug was encapsulated in poly(lactic-co-glycolic acid) (PLGA) microparticles with or without 5-fluorouracil (5-FU). However, the encapsulation efficiency of 5-FU was low (19%) and increased to 30% when the drug was encapsulated with Paclitaxel. The mean particle size of microspheres was 2.5 μm and were spherical in shape. The in vitro release of both 5-FU and Paclitaxel from the microspheres was relatively fast initially followed by a slower and more controlled release. The cytotoxic activity of Paclitaxel microspheres was far greater compared to either the microspheres containing 5-FU+Paclitaxel or 5-FU alone. Overall results demonstrated that incorporation of Paclitaxel or 5-FU in microspheres enhances the cytotoxicity in more controlled manner compared to that of free drugs and also that careful consideration should be made when combining drugs acting in different phases of cell cycle.