Ceramic nanovector based on layered double hydroxide: Attributes, physiologically relevant compositions and surface activation

Drug delivery platforms based on nano sized geometries are nanovectors which promise a revolutionary impact on the diagnosis and therapy of various types of cancers and diseases. To date, various polymeric platforms have been the focus of intense research, but the development of inorganic biohybrid nanoparticles for therapeutics and molecular imaging are at a stage of infancy. A unique inorganic ceramic, based on layered double (Mg²⁺,Al ³⁺) hydroxide nanoparticles (or LDHN; 50-150 nm), has positively charged layers that can be ionically bonded to negatively charged anions or biomolecular agents within the interlayer space. Since 2001, these intercalated or biohybridised LDHN have been evaluated as a passive vector for drug and non-viral gene delivery. The focus of this paper is on identifying the attributes of LDHN as a passive delivery platform, judicious selections of physiologically relevant compositions and issues in synthesis, and surface activation of LDHN; the latter being a critical first step in the LDHN surface functionalisation process, with all covalent linkages. After a brief description of the LDH structure and unique attributes of LDHN as a passive delivery platform, the issues and advantages of a robust LDHN surface functionalisation process for active targeting are identified. Next, to ascertain safety and biocompatibility, and dictated by physiological relevance with respect to essentialness and toxicity, the judicious selection of (Mg²⁺,Fe ³⁺) and (Zn²⁺,Fe³⁺) LDH compositions is made. A preliminary precipitation synthesis of these compositions affirms that while phase pure and crystalline precipitates of (Mg²⁺,Fe³⁺) LDHN readily form under high supersaturation at constant pH (>12), the same may be achieved for (Zn²⁺,Fe³⁺) LDHN by circumventing the formation of ZnO and polymerisation of Fe(OH)₃ at constant pH (6-7) but low supersaturation. Finally, the surface activation of (Mg ²⁺,Al³⁺) LDHN is demonstrated by a bimolecular, nucleophilic substitution type reaction using acryloyl chloride; a process which will facilitate the covalent conjugations of linkers and targeting ligands.