Silicate Esters of Paclitaxel and Docetaxel: Synthesis, Hydrophobicity, Hydrolytic Stability, Cytotoxicity, and Prodrug Potential

Wohl, Adam R.; Michel, Andrew R.; Kalscheuer, Stephen; Macosko, Christopher W.; Panyam, Jayanth; Hoye, Thomas R.

doi:10.1021/jm401708f

Cited by 27 publications

(31 citation statements)

References 36 publications

(69 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although many of these conditions have been optimized for specific block copolymer chemistries and drug loading, several standard practices have been universally adopted for FNP protocols to achieve stable kinetically trapped nanoparticles. These include the use of tetrahydrofuran (THF) and pure water respectively as the solvent and nonsolvent as well as large reservoir-to-solvent volume ratios [8, 9, 49, 50]. Matching Hildebrand solubility parameters is a good indicator of miscibility, and thus polymers and drugs with Hildebrand solubility parameters similar to that of THF will likely be suitable for standard FNP protocols.…”

Section: Resultsmentioning

confidence: 99%

Facile assembly and loading of theranostic polymersomes via multi-impingement flash nanoprecipitation

Allen

Osorio

Liu

et al. 2017

Journal of Controlled Release

141

View full text Add to dashboard Cite

Flash nanoprecipitation (FNP) has proven to be a powerful tool for the rapid and scalable assembly of solid-core nanoparticles from block copolymers. The process can be performed using a simple confined impingement jets mixer and provides an efficient and reproducible method of loading micelles with hydrophobic drugs. To date, FNP has not been applied for the fabrication of complex or vesicular nanoarchitectures capable of encapsulating hydrophilic molecules or bioactive protein therapeutics. Here, we present FNP as a single customizable method for the assembly of bicontinuous nanospheres, filomicelles and vesicular, multilamellar and tubular polymersomes from poly(ethylene glycol)-bl-poly(propylene sulfide) block copolymers. Multiple impingements of polymersomes assembled via FNP were shown to decrease vesicle diameter and polydispersity, allowing gram-scale fabrication of monodisperse polymersomes within minutes. Furthermore, we demonstrate that FNP supports the simultaneous loading of both hydrophobic and hydrophilic molecules respectively into the polymersome membrane and aqueous lumen, and encapsulated enzymes were found to be released and remain active following vesicle lysis. As an example application, theranostic polymersomes were generated via FNP that were dual loaded with the immunosuppressant rapamycin and a fluorescent dye to link targeted immune cells with the elicited immunomodulation of T cells. By expanding the capabilities of FNP, we present a rapid, scalable and reproducible method of nanofabrication for a wide range of nanoarchitectures that are typically challenging to assemble and load with therapeutics for controlled delivery and theranostic strategies.

show abstract

Section: Resultsmentioning

confidence: 99%

Facile assembly and loading of theranostic polymersomes via multi-impingement flash nanoprecipitation

Allen

Osorio

Liu

et al. 2017

Journal of Controlled Release

141

View full text Add to dashboard Cite

show abstract

“…13 As we described there, “silicates having faster rates of hydrolysis [cf. Table 1] tend to show cytotoxicities similar to those of the parent taxane.…”

Section: Resultsmentioning

confidence: 99%

“…13, 15 Paclitaxel was obtained from Phytogen Life Sciences. Water (H 2 O, HPLC grade), tetrahydrofuran (THF, HPLC grade), and acetonitrile (ACN, HPLC grade) were purchased from Sigma-Aldrich and used as received.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Nanoparticles Containing High Loads of Paclitaxel-Silicate Prodrugs: Formulation, Drug Release, and Anticancer Efficacy

Han

Michel

Lee³

et al. 2015

Mol. Pharmaceutics

Self Cite

View full text Add to dashboard Cite

We have investigated particle size, interior structure, drug release kinetics, and anticancer efficacy of PEG-b-PLGA-based nanoparticles loaded with a series of paclitaxel (PTX) silicate prodrugs [PTX-Si(OR)3]. Silicate derivatization enabled us to adjust the hydrophobicity and hydrolytic lability of the prodrugs by the choice of the alkyl group (R) in the silicate derivatives. The greater hydrophobicity of these prodrugs allows for the preparation of nanoparticles that are stable in aqueous dispersion even when loaded with up to ca. 75 wt% of the prodrug. The hydrolytic lability of silicates allows for facile conversion of prodrugs back to the parent drug, PTX. A suite of eight PTX-silicate prodrugs was investigated; nanoparticles were made by flash nanoprecipitation (FNP) using a confined impingement jet mixer with a dilution step (CIJ-D). The resulting nanoparticles were 80–150 nm in size with a loading level of 47–74 weight percent (wt%) of a PTX-silicate, which corresponds to 36–59 effective wt % of free PTX. Cryogenic transmission electron microscopy images show that particles are typically spherical with a core-shell structure. Prodrug/drug release profiles were measured. Release tended to be slower for prodrugs having greater hydrophobicity and slower hydrolysis rate. Nanoparticles loaded with PTX-silicate prodrugs that hydrolyze most rapidly showed in vitro cytotoxicity similar to that of the parent PTX. Nanoparticles loaded with more labile silicates also tended to show greater in vivo efficacy.

show abstract

“…Targeted therapy based on distinct tumor types faces a major challenge. As classification has been primarily based on histology of tumor, targeted therapy has not been effective in treating tumors with similar histology [6, 227]. Similarly, several Dtx derivatives with better targetibility and stability were developed such as CD44 targeted-hyaluronic acid based derivatives [228].…”

Section: Prodrug Approach: Analog / Chemical Conjugation For Cancementioning

confidence: 99%

Novel delivery approaches for cancer therapeutics

Mitra

Agrahari

Mandal

et al. 2015

Journal of Controlled Release

130

View full text Add to dashboard Cite

Currently, a majority of cancer treatment strategies are based on the removal of tumor mass mainly by surgery. Chemical and physical treatments such as chemo- and radiotherapies have also made a major contribution in inhibiting rapid growth of malignant cells. Furthermore, these approaches are often combined to enhance therapeutic indices. It is widely known that surgery, chemo- and radiotherapy also inhibit normal cells growth. In addition, these treatment modalities are associated with severe side effects and high toxicity which in turn lead to low quality of life. This review encompasses novel strategies for more effective chemotherapeutic delivery aiming to generate better prognosis. Currently, cancer treatment is a highly dynamic field and significant advances are being made in the development of novel cancer treatment strategies. In contrast to conventional cancer therapeutics, novel approaches such as ligand or receptor based targeting, triggered release, intracellular drug targeting, gene delivery, cancer stem cell therapy, magnetic drug targeting and ultrasound-mediated drug delivery, have added new modalities for cancer treatment. These approaches have led to selective detection of malignant cells leading to their eradication with minimal side effects. Lowering, multi-drug resistance and involving influx transportation in targeted drug delivery to cancer cells can also contribute significantly in the therapeutic interventions in cancer.

show abstract

Silicate Esters of Paclitaxel and Docetaxel: Synthesis, Hydrophobicity, Hydrolytic Stability, Cytotoxicity, and Prodrug Potential

Cited by 27 publications

References 36 publications

Facile assembly and loading of theranostic polymersomes via multi-impingement flash nanoprecipitation

Facile assembly and loading of theranostic polymersomes via multi-impingement flash nanoprecipitation

Nanoparticles Containing High Loads of Paclitaxel-Silicate Prodrugs: Formulation, Drug Release, and Anticancer Efficacy

Novel delivery approaches for cancer therapeutics

Contact Info

Product

Resources

About