Development of a bone targeted thermosensitive liposomal doxorubicin formulation based on a bisphosphonate modified non-ionic surfactant

Abstract

Bone is among the most common sites of metastasis in cancer patients, so it is an urgent need to develop drug delivery systems targeting tumor bone metastasis with the feature of controlled release. This study aimed to delivery of thermosensitive liposomal doxorubicin to bone for tumor metastasis treatment. First, Brij78 (polyoxyethylene stearyl ether) was conjugated with Pamidronate (Pa). By incorporating Pa-Brij78 to DPPC/Chol liposomes, we developed Pa surface functionalized liposomes. The Pa-Brij78/DPPC/Chol liposomes (PB-liposomes) exhibited a stronger binding affinity to hydroxyapatite (HA), a major component of bone, than Brij78/DPPC/Chol liposomes (B-liposomes). Doxorubicin (Dox) was then encapsulated in PB-liposomes and the results demonstrated complete release of Dox from PB-liposomes or the complex of HA/PB-liposomes within 10 min at 42 °C. Next, human lung cancer A549 cells were treated with the thermosensitive complex of HA/PB-liposomes/Dox to mimic tumor bone metastasis treatment through bone targeted delivery of therapeutic agents. Pre-incubation of HA/PB-liposomes/Dox with mild heat at 42 °C induced subsequent higher cytotoxicity to A549 cells than incubation of the same complex at 37 °C, suggesting more active drug release triggered by heat. In conclusion, we synthesized a novel surfactant Pa-Brij78 and it has the potential to be used for development of a bone targeted thermosensitive liposome formulation for treatment of tumor bone metastasis.

Inhalation of nanoparticle-based drug for lung cancer treatment: Advantages and challenges

“…Liposome can be prepared in different sizes ranging from 50 nm to more than 1000 nm, depending on the composition of phospholipid and cholesterol molecules used. The presences of phospholipid layers make liposome an ideal carrier to encapsulate water insoluble drugs especially most chemotherapeutic drugs such as paclitaxel and doxorubicin [39,47,48]. Paclitaxel liposome consisting of dilauroylphosphatidylcholine (DLPC) at drug-tolipid ratio of 1:10 (w/w) were prepared in butanol and lyophilized to prepare a DPI formulation.…”

Targeted nanomedicines for the treatment of bone disease and regeneration

“…So, targeted delivery of chemotherapeutic with BP‐conjugated thermo‐sensitive liposomes seems a good therapeutic opportunity. To this end, Song et al designed thermo‐sensitive liposomes containing doxorubicin and conjugated them with pamidronate 213 . As expected the pamidronate conjugated liposomes exhibited stronger binding affinity to HA compared to nonconjugated ones.…”

“…As expected the pamidronate conjugated liposomes exhibited stronger binding affinity to HA compared to nonconjugated ones. They also showed that doxorubicin was completely released when liposomes were heated up to 42°C either alone or in combination with HA 213 …”

New Progress in Improving the Delivery Methods of Bisphosphonates in the Treatment of Bone Tumors

“…Similarly, Song et al 61 introduced Brij78 (polyoxyethylene stearyl ether) and pamidronate (Pa)-conjugated PA-Brij78 into DPPC/Chol liposomes to prepare PA surface functional liposomes. The in vitro binding of PB liposomes embedded with adriamycin to hyaluronic acid (HA), the temperature-dependent release of doxorubicin and the cytotoxicity were studied.…”