Manipulation of the C(22)-C(27) region of rapamycin: Stability issues and biological implications

Nelson, Frances C.; Stachel, Shawn J.; Eng, C. P.; Sehgal, Suren N.

doi:10.1016/s0960-894x(98)00735-5

Cited by 28 publications

(11 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Generally, phosphate buffer saline (PBS) with pH 7.4 is employed as a release medium to study in vitro release of nanoparticles. RPM is reported to be unstable in PBS due to alkaline hydrolysis of lactam ring leading to ring opening (Nelson et al, 1999). Although the solubility of RPM is very low in a buffer, it is sufficient to undergo hydrolysis.…”

Section: In Vitro Drug Release From Nanoparticlesmentioning

confidence: 99%

Co-delivery of rapamycin- and piperine-loaded polymeric nanoparticles for breast cancer treatment

et al. 2015

View full text Add to dashboard Cite

P-glycoprotein (P-gp) efflux is the major cause of multidrug resistance (MDR) in tumors when using anticancer drugs, moreover, poor bioavailability of few drugs is also due to P-gp efflux in the gut. Rapamycin (RPM) is in the clinical trials for breast cancer treatment, but its P-gp substrate property leads to poor oral bioavailability and efficacy. The objective of this study is to formulate and evaluate nanoparticles of RPM, along with a chemosensitizer (piperine, PIP) for improved oral bioavailability and efficacy. Poly(d,l-lactide-co-glycolide) (PLGA) was selected as polymer as it has moderate MDR reversal activity, which may provide additional benefits. The nanoprecipitation method was used to prepare PLGA nanoparticles with particle size below 150 nm, loaded with both drugs (RPM and PIP). Prepared nanoparticles showed sustained in vitro drug release for weeks, with initial release kinetics of zero order with non-Fickian transport, subsequently followed by Higuchi kinetics with Fickian diffusion. An everted gut sac method was used to study the effect of P-gp efflux on drug transport. This reveals that the uptake of the RPM (P-gp substrate) has been increased in the presence of chemosensitizer. Pharmacokinetic studies showed better absorption profile of RPM from polymeric nanoparticles compared to its suspension counterpart and improved bioavailability of 4.8-folds in combination with a chemosensitizer. An in vitro cell line study indicates higher efficacy of nanoparticles compared to free drug solution. Results suggest that the use of a combination of PIP with RPM nanoparticles would be a promising approach in the treatment of breast cancer.

show abstract

Section: In Vitro Drug Release From Nanoparticlesmentioning

confidence: 99%

Co-delivery of rapamycin- and piperine-loaded polymeric nanoparticles for breast cancer treatment

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Sirolimus (rapamycin) is a carboxylic lactone-lactam macrolide derived from an actinomycete (Streptomyces hygroscopicus), and the bulk powder consists of three isomeric forms (-α, -β and -γ). The chemical stability of the drug molecule appears to be sensitive to various factors such as pH (27) and organic solvents (28). Obviously, the fusion process of sirolimus polymeric microparticles using infrared radiation could have an impact on chemical stability and consequently alter the stent's immunosuppressive capability.…”

Section: Edpdt and Fusion Processmentioning

confidence: 99%

The Application of Electrostatic Dry Powder Deposition Technology to Coat Drug-Eluting Stents

et al. 2009

View full text Add to dashboard Cite

show abstract

“…In case of sirolimus eluting stent, this medium is found to be inappropriate since sirolimus hydrolyses to form newer compounds with opened lactam ring at alkaline pH and buffer salts. It is reported that the stability of sirolimus is very low if buffer with pH 7.4 as a medium for release studies is used [10]. The lower stability is reasoned due to hydrolytic degradation of sirolimus in buffer solutions though the solubility of sirolimus in aqueous solution is very low [11][12][13].…”

Section: Introductionmentioning

confidence: 99%

The release kinetics of drug eluting stents containing sirolimus as coated drug: Role of release media

Naseerali

Hari

Sreenivasan

2010

Journal of Chromatography B

View full text Add to dashboard Cite

Manipulation of the C(22)-C(27) region of rapamycin: Stability issues and biological implications

Cited by 28 publications

References 13 publications

Co-delivery of rapamycin- and piperine-loaded polymeric nanoparticles for breast cancer treatment

Co-delivery of rapamycin- and piperine-loaded polymeric nanoparticles for breast cancer treatment

The Application of Electrostatic Dry Powder Deposition Technology to Coat Drug-Eluting Stents

The release kinetics of drug eluting stents containing sirolimus as coated drug: Role of release media

Contact Info

Product

Resources

About