Monthly Archives: July 2013

New publication combines PTX delivery via PolyVivo AK09 along with ultrasound techniques for treatment of cancer

Publication put out as:

Rapoport, Natalya, Allison Payne, Christopher Dillon, Jill Shea, Courtney Scaife, and Roohi Gupta. “Focused ultrasound-mediated drug delivery to pancreatic cancer in a mouse model.” Journal of Therapeutic Ultrasound 1, no. 1 (2013): 11.

“Abstract 

Background 

Many aspects of the mechanisms involved in ultrasound-mediated therapy remain obscure. In particular, the relative roles of drug and ultrasound, the effect of the time of ultrasound application, and the effect of tissue heating are not yet clear. The current study was undertaken with the goal to clarify these aspects of the ultrasound-mediated drug delivery mechanism. 

Methods 

Focused ultrasound-mediated drug delivery was performed under magnetic resonance imaging guidance (MRgFUS) in a pancreatic ductal adenocarcinoma (PDA) model grown subcutaneously in nu/nu mice. Paclitaxel (PTX) was used as a chemotherapeutic agent because it manifests high potency in the treatment of gemcitabine-resistant PDA. Poly(ethylene oxide)-co-poly(D,L-lactide) block copolymer stabilized perfluoro-15-crown-5-ether nanoemulsions were used as drug carriers. MRgFUS was applied at sub-ablative pressure levels in both continuous wave and pulsed modes, and only a fraction of the tumor was treated. 

Results 

Positive treatment effects and even complete tumor resolution were achieved by treating the tumor with MRgFUS after injection of nanodroplet encapsulated drug. The MRgFUS treatment enhanced the action of the drug presumably through enhanced tumor perfusion and blood vessel and cell membrane permeability that increased the drug supply to tumor cells. The effect of the pulsed MRgFUS treatment with PTX-loaded nanodroplets was clearly smaller than that of continuous wave MRgFUS treatment, supposedly due to significantly lower temperature increase as measured with MR thermometry and decreased extravasation. The time of the MRgFUS application after drug injection also proved to be an important factor with the best results observed when ultrasound was applied at least 6 h after the injection of drug-loaded nanodroplets. Some collateral damage was observed with particular ultrasound protocols supposedly associated with enhanced inflammation. 

Conclusion 

This presented data suggest that there exists an optimal range of ultrasound application parameters and drug injection time. Decreased tumor growth, or complete resolution, was achieved with continuous wave ultrasound pressures below or equal to 3.1 MPa and drug  injection times of at least 6 h prior to treatment. Increased acoustic pressure or ultrasound  application before or shortly after drug injection gave increased tumor growth when compared to other protocols.”

See the full-text here: http://www.jtultrasound.com/content/pdf/2050-5736-1-11.pdf

mPEG-PLA as PTX delivery vehicle

Research below describes how to use mPEG-PLA block copolymer as a means to formulate nanoparticles for delivery of poorly soluble paclitaxel.  See full text here http://www.nanoscalereslett.com/content/pdf/1556-276X-8-301.pdf

Abstract:

We present a dialysis technique to direct the self-assembly of paclitaxel (PTX)-loaded   nanoparticles (NPs) using methoxypolyethylene glycol-poly(d,l-lactide) (MPEG-PLA)   and PLA, respectively. The composition, morphology, particle size and zeta potential,   drug loading content, and drug encapsulation efficiency of both PTX-PLA NPs and PTX-MPEG-PLA   NPs were characterized by X-ray diffraction, Fourier transform infrared spectroscopy,   transmission electron microscopy, dynamic light scattering, electrophoretic light   scattering, and high-performance liquid chromatography. The passive targeting effect   and in vitro cell viability of the PTX-MPEG-PLA NPs on HeLa cells were demonstrated   by comparative cellular uptake and MTT assay of the PTX-PLA NPs. The results showed   that the PTX-MPEG-PLA NPs and PTX-PLA NPs presented a hydrodynamic particle size of   179.5 and 441.9 nm, with a polydispersity index of 0.172 and 0.189, a zeta potential   of -24.3 and -42.0 mV, drug encapsulation efficiency of 18.3% and 20.0%, and drug-loaded   content of 1.83% and 2.00%, respectively. The PTX-MPEG-PLA NPs presented faster release   rate with minor initial burst compared to the PTX-PLA NPs. The PTX-MPEG-PLA NPs presented   superior cell cytotoxicity and excellent cellular uptake compared to the PTX-PLA NPs.   These results suggested that the PTX-MPEG-PLA NPs presented more desirable characteristics   for sustained drug delivery compared to PTX-PLA NPs

diblock mPEG-PLGA as carrier for zeylenone

Graphical Abstract Shown: Find out more at: http://www.sciencedirect.com/science/article/pii/S0378517313002998

zeylenone deliveryXiao Hu et. al. prepared zeylenone loaded mPEG-PLGA micelles by forming a thin film via rotary evaporation from a DCM solution, rehydrating in 50C water, and filtering down to 200nm size.  The micelles were freeze dried and noted to have the following properties (average n=3): Drug loading (%)-2.55; Encapsulation efficiency (%)- 97.12; Solubility >2 mg/ml; Size (nm) in water 34.46; PDI in water 0.213; Zeta potential in water −24.90; Size (nm) in serum 53.51; Zeta potential in serum−31.6. (X Hu, R Han, LH Quan, CY Liu, YH Liao – International Journal of Pharmaceutics Volume 450, Issues 1–2, 25 June 2013, Pages 331–337).

The impact of these drug-carriers on tumors in BALB/c mouse model is shown in the graphical abstract. This research shows the promise of the use of mPEG-PLGA as a carrier for chemotherapeutic compounds.