Thermoreversible Pluronic® F127-based hydrogel containing liposomes for the controlled delivery of paclitaxel: in vitro drug release, cell cytotoxicity, and uptake studies

Abstract

Purpose To develop an in situ gel system comprising liposome-containing paclitaxel (PTX) dispersed within the thermoreversible gel (Pluronic ® F127 gel) for controlled release and improved antitumor drug efficiency. Methods The dialysis membrane and membrane-less diffusion method were used to investigate the in vitro drug release behavior. Differential scanning calorimetry (DSC) thermal analysis was used to investigate the “micellization” and “sol/gel transition” process of in situ gel systems. In vitro cytotoxicity and drug uptake in KB cancer cells were determined by MTT, intercellular drug concentration, and fluorescence intensity assay. Results The in vitro release experiment performed with a dialysis membrane model showed that the liposomal gel exhibited the longest drug-release period compared with liposome, general gel, and commercial formulation Taxol ® . This effect is presumably due to the increased viscosity of liposomal gel, which has the effect of creating a drug reservoir. Both drug and gel release from the in situ gel system operated under zero-order kinetics and showed a correlation of release of PTX with gel, indicating a predominating release mechanism of the erosion type. Dispersing liposomes into the gel replaced larger gel itself for achieving the same gel dissolution rate. Both the critical micelle temperature and the sol/gel temperature, detected by DSC thermal analysis, were shifted to lower temperatures by adding liposomes. The extent of the shifts depended on the amount of embedded liposomes. MTT assay and drug uptake studies showed that the treatment with PTX-loaded liposomal 18% Pluronic F127 yielded cytotoxicities, intercellular fluorescence intensity, and drug concentration in KB cells much higher than that of conventional liposome, while blank liposomal 18% Pluronic F127 gel was far less than the Cremophor EL ® vehicle and empty liposomes. Conclusions A thermosensitive hydrogel with embedded liposome is a promising carrier for hydrophobic anticancer agents, to be used in parenteral formulations for treating local cancers.

Inhibition of bone loss with surface-modulated, drug-loaded nanoparticles in an intraosseous model of prostate cancer

“…In this study, animals received a single dose of PTX-CrEL, and it is possible that only a subtherapeutic level of PTX reached the metastatic sites in bone, stimulating the proliferation of cancer cells, as some teams have reported [54, 55]. Unlike PTX-CrEL (PTX release of 70% in 4 hours and 100% in 12 hours) [56], PTX-NPs provided a continuous localized dose of PTX (~0.7% per day), thus providing the comparison between fast- and sustained-release formulations of PTX on their efficacy. NP albumin-bound (nab) PTX, despite having smaller particle size (~130 nm) than the openings of the bone marrow capillary fenestrations (~170 nm), has in fact been shown to increase the incidence of metastasis, including to bones, in an animal model of breast cancer metastasis [57].…”

PEO–PPO Diblock Copolymers Protect Myoblasts from Hypo-Osmotic Stress In Vitro Dependent on Copolymer Size, Composition, and Architecture

“…A representative class of amphiphilic block copolymers is triblock copolymers formed from poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO), also known as Pluronics or poloxamers 1 . Poloxamers have been used as versatile biomaterials such as thermosensitive hydrogels 2,3 , drug delivery carriers 4,5 , and chemosensitization agents for cancer therapy 6–8 . Poloxamer 188 (P188), an 8400 g/mol PEO-PPO-PEO triblock copolymer comprising two segments of 75 PEO units on either side of a segment with 30 PPO units, has demonstrated membrane stabilization characteristics in multiple scenarios.…”

Delivery of enteric neural progenitors with 5-HT4 agonist-loaded nanoparticles and thermosensitive hydrogel enhances cell proliferation and differentiation following transplantation in vivo

“…Caicco et al [38] observed that poly(lactic-co-gycolic) acid microsphere-encapsulated cyclosporine A (CsA) released from hyaluronan-methylcellulose hydrogel was prolonged for a period 3-4 weeks following epi-cortical delivery in vivo , whereas particulate CsA extended release to days from hours for solubilized CsA [38]. Nie et al [36] formulated the anticancer drug, paclitaxel (PTX), into liposomal nanoparticles in PF-127 hydrogel to achieve the desired drug release rate. They found that drug release was significantly prolonged from liposomal-encapsulated PTX immobilized within PF-127 hydrogel compared to liposomal PTX alone or PTX in PF-127, leading to substantial cytotoxic benefit in a cancer cell line [36].…”

“…Nie et al [36] formulated the anticancer drug, paclitaxel (PTX), into liposomal nanoparticles in PF-127 hydrogel to achieve the desired drug release rate. They found that drug release was significantly prolonged from liposomal-encapsulated PTX immobilized within PF-127 hydrogel compared to liposomal PTX alone or PTX in PF-127, leading to substantial cytotoxic benefit in a cancer cell line [36]. Liposomes may act as a reservoir for sustained drug release and PF-127 may enhance penetration of liposomal drugs to improve their efficacy.…”

“…PF-127 hydrogel has recently been tested for in situ delivery of neural precursor cells and has demonstrated improved cell survival and reduced host immune response [31-33]. Furthermore, hydrogel containing drug-loaded nanoparticles has been shown to provide sustained release of insulin [34, 35] and anticancer drugs [36, 37] in vitro , and cyclosporine A (CsA) in vivo [38]. …”