Formulation of dacarbazine-loaded cubosomes. Part III. Physicochemical characterization

Abstract

The purpose of this study was to investigate the physicochemical properties of dacarbazine-loaded cubosomes. The drug-loaded cubosome nanocarriers were prepared by a fragmentation method and then freeze dried. They were then characterized for size, morphology, thermal behavior, and crystallography using dynamic light scattering, transmission electron microscopy (TEM), differential scanning calorimetry (DSC), and powder X-ray diffraction (PXRD), respectively. The drug loading and encapsulation efficiency were determined by UV spectrophotometry. The results showed that the prepared dacarbazine-loaded cubosomes had mean diameters ranging from 86 to 106 nm. In addition to the TEM, the characteristic peaks from PXRD data suggested that the freeze-dried nanoformulations were indeed cubic in nature. DSC and PXRD analysis suggested the 0.06 or 0.28% w/w actual drug loaded inside cubosomes was in the amorphous or molecular state. These physicochemical characteristics would affect the nanoformulation shelf-life, efficacy, and safety.

Fig. 1

Selected physicochemical properties of key ingredients used in the cubosome nanoformulation: a Dacarbazine, (DTIC, C₆H₁₀N₆O, pka: 4.42, MW: 182.18, mp: ~205°C, water solubility: 4220 mg/L, logP = −1.6; 38); b Monoolein (GMO, C₂₁H₃₀O₄)

Fig. 2

Typical TEM image of dacarbazine loaded cubosome nanocarrier: a a population of cubosomes. b Single cubsome to better view the cubic structure. Scale bar 200 nm

Fig. 3

PXRD pattern of native DTIC

Fig. 4

PXRD pattern of four samples: first drug-free or blank cubosome (number 1, sample F1−) and corresponding master cubsome formulation based on formulation variable (number 2, sample F1+), second blank cubosome (number 3, sample F2−) and corresponding master formulation based on process parameters (number 4, sample F2+)

Fig. 5

DSC Thermograms of a native monoolein (GMO), b native poloxamer 407 (F 127), c native dacarbazine (DTIC), d cubosome formulation based on formulation variables (F1+), and e cubosome formulation based on process parameters (F2+). Downwards direction endothermic, upwards direction exothermic