Co-delivery of paclitaxel and cisplatin in poly(2-oxazoline) polymeric micelles: Implications for drug loading, release, pharmacokinetics and outcome of ovarian and breast cancer treatments

Abstract

Concurrent delivery of multiple drugs using nanoformulations can improve outcomes of cancer treatments. Here we demonstrate that this approach can be used to improve the paclitaxel (PTX) and alkylated cisplatin prodrug combination therapy of ovarian and breast cancer. The drugs are co-loaded in the polymeric micelle system based on amphiphilic block copolymer poly(2methyl-2-oxazoline-block-2-butyl-2-oxazoline-block-2-methyl-2-oxazoline) (P(MeOx-b-BuOxb-MeOx). A broad range of drug mixing ratios and exceptionally high two-drug loading of over 50 #

High Capacity poly(2-oxazoline) formulation of TLR 7/8 agonist extends survival in a chemo-insensitive, metastatic model of Lung Adenocarcinoma

“…The drug synergy for different combination ratios was studied using the combination index (CI) theorem (isobologram equation) of Chou and Talalay, which states that a CI value of less than 1 represents synergism, whereas CI value greater than 1 indicates antagonism. Of note, the superadditive therapeutic effect of drug combinations is strongly influenced by the drug ratios (15,24). Interestingly, every feed ratio (4:8 through 9:3) of the C 6 CP/AZD7762 combination yielded CI < 0.3 for Fa ranging from 0.1 to 0.9, suggesting a strong synergy of the cotreatment.…”

“…POx is an amphiphilic triblock-copolymer composed of one hydrophobic block of poly(2-butyl-2-oxazoline) (BuOx) flanked by two hydrophilic blocks of (2-methyl-2-oxazoline) (MeOx). POx micelles exhibit an exceptionally high solubilization capacity for water-insoluble drugs, in both singular and multi-drug combinations (14,15). We leveraged the characteristic sub-100 nm size of POx micelles to decrease the dose-limiting toxicity of the TLR agonist by passive targeting to the tumor.…”

Poly(2-ethyl-2-oxazoline-co-N-propylethylene imine)s by controlled partial reduction of poly(2-ethyl-2-oxazoline): synthesis, characterization and cytotoxicity

“…Poly(2-oxazoline)s as a very diverse polymer family have seen a tremendous increase of interest for the preparation of biomaterials. 37 Recent years have seen the first-in-man clinical trials for POxbased polymer drug conjugates 38 , very significant advances in preclinical studies of POx based micellar drug delivery systems [39][40][41][42][43][44][45][46][47][48] , and hydrogels for various biomedical applications. [49][50][51][52][53] The presented results add another layer of chemical versatility to this already multifarious polymer family, which are particular interesting potential application for the complexation of oppositely charged biomacromolecules such as proteins and polynucleic acids.…”

4-n-Butylresorcinol-Based Linear and Graft Polymethacrylates for Arbutin and Vitamins Delivery by Micellar Systems

“…Recently, polymeric micelles gained great attention as carriers. The literature broadly reports the use of micelles as effective delivery systems for anti-cancer drugs (doxorubicin [12,13], paclitaxel [14,15]), anti-inflammatory (e.g., indomethacin [16][17][18]), or antibacterial drugs (erythromycin [19]) as well as for the active substances used in cosmetology (vitamin K [20,21], vitamin D [22], vitamin A [23][24][25][26], and vitamin series of grafted copolymers was also obtained by using "click" chemistry reaction as "grafting onto" method. For this purpose, multifunctional copolymers with alkyne functionalized HEMA (AlHEMA) were obtained.…”