Demixing and crystallization of DODAB in DPPC-DODAB binary mixtures.

The crystallization mechanism of one lipid component within multicomponent lipid mixtures remains unclear. To shed light on this issue, we studied the demixing and crystallization behaviors of a binary lipid system using neutral dipalmitoylphosphatidylcholine (DPPC) and cationic dioctadecyldimethylammonium bromide (DODAB) as model molecules. The results indicate that when DODAB is no more than equimolar (e.g., DPPC/DODAB = 2/1 and 1/1), DPPC is miscible with DODAB and hinders the crystallization of DODAB, and the samples undergo reversible gel-fluid phase transitions upon heating and cooling. However, when DODAB is dominant in the mixture (DPPC/DODAB = 1/2), cooling of the mixed fluid phase results in the formation of a DODAB-rich gel domain and a DPPC-DODAB mixed gel domain. Such phase-separated mixed gels can undergo further demixing and crystallization, producing a DODAB-rich crystalline domain and a DPPC-rich tilted gel domain upon prolonged (or plus low-temperature) incubation. Besides, evidence has been given that the crystallized DODAB-rich domain remains in the same lipid bilayer as the DPPC-rich domain. All the three binary lipid mixtures can hold large amounts of water in the lipid interlamellar regions, allowing the incorporation of a large number of water-soluble substances such as DNA or proteins, which can be used for the fabrication of functional biofilms and biomaterials. Influences of water content and salt concentration on the phase structures (e.g., repeat distances) of the binary mixtures have also been studied.

[Design and analyze mathematical algorithms of intestinal absorption and metabolism of multicomponent drug].

Evaluation of the permeability mainly focuses on intestinal absorption in biopharmaceutics classification system (BCS). It is more complicated that the absorption and metabolism under multicomponent environment in biopharmaceutics classification system of Chinese materia medica (CMMBCS) compared with single component environment, which needs suitable mathematical models to be described. Therefore, with full consideration of existing single component mathematical algorithm combining with the characteristics of intestinal absorption and metabolism, we explored and designed a new mathematical algorithm of intestinal absorption and metabolism of multicomponent drug. Then we put forward a new coefficient, P (influence), the relative change rate of the single component's intestinal absorption and metabolism under multicomponent environment compared with single component environment, which described the influences of intestinal absorption and metabolism of the component under multicomponent environment. Moreover, P (influence) highlights the distinctive characteristics of multicomponent drug's intestinal absorption and metabolism, and lays the foundation for the construction of CMMBCS.

Competitive molecular interaction among paeonol-loaded liposomes: differential scanning calorimetry and synchrotron X-ray diffraction studies.

Thermotropic phase behavior of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) liposomes containing 5 mol% cholesterol, or 5 mol% stigmasterol, or 5 mol% paeonol have been investigated by differential scanning calorimetry (DSC) and synchrotron X-ray diffraction (XRD) techniques, to investigate the competitive molecular interaction among paeonol-loaded liposomes. The results show that both sterol and paeonol can incorporate into hydrophobic region and interact with acyl chains of DPPC. Both 5 mol% sterols and 5 mol% paeonol can promote the formation of rippled gel phase of DPPC liposomes at room temperature. 5 mol% paeonol can induce the occurrence of phase separation in DPPC liposomes, but 5 mol% cholesterol or 5 mol% stigmasterol cannot induce this phenomenon. Both the repeat distance and the correlation length of paeonol-poor domain are larger than those of coexisted paeonol-rich domain. Both calorimetric data and SAXS patterns show that sterols have more favorable, stabilizing interactions with DPPC than paeonol, implying that high concentrations of sterols will have a negative effect on the loading of paeonol. In addition, calorimetric data show that cholesterol have a little more favorable, stabilizing interactions with DPPC than stigmasterol. The results of this study will play an important role in optimizing the formulation of paeonol-loaded liposomes.

Regional cooperativity in the phase transitions of dipalmitoylphosphatidylcholine bilayers: the lipid tail triggers the isothermal crystallization process.

We have a long-standing interest to explore the answer of the question: Which part of the amphiphilic molecule triggers the phase transition of the self-assembled aggregates consisting of these amphiphiles? This is an important issue regarding the phase transition kinetics of amphiphiles. To this end, we studied the phase transition behaviors of dipalmitoylphosphatidylcholine (DPPC) by differential scanning calorimetry, synchrotron X-ray scattering, Fourier transform infrared spectroscopy, and image analysis. We found that different parts (head, interface, and tail) of DPPC molecules all exhibit nonsynchronous changes during the sub-, pre-, and main transitions. Particular efforts have been devoted to studying the isothermal subgel (L(c')) formation process. It was found that only the lipid interface and tail regions change, and only when the rearrangement of the lipid hydrocarbon chain packing reaches a certain extent can the interfacial C═O groups be induced to undergo vibrational environment changes. The result means that the hydrocarbon tail is the part that triggers the gel (L(ß')) to L(c') phase transition. The present work deepens our understanding on the phase transition mechanisms of DPPC and may shed light on those of other phospholipids and other types of amphiphiles.