Stability issues and approaches to stabilised nanoparticles based drug delivery system.

Nanoparticles form the fundamental building blocks for many exciting applications in various scientific disciplines due to its unique features such as large surface to mass ratio, targeting potential, ability to adsorbed and carry other compound which makes them suitable for biomedical applications. However, the problem of the large-scale synthesis of nanoparticles remains challenging due to physical instability associated with nanoparticles which lead to generation of aggregates particles with high polydispersity index (PDI) indicating low particle homogeneity and eventually loss of their special nanoscale properties. The stabilisation concept can be generated by repulsive electrostatic force, which nanoparticles experience, when they are surrounded by a double layer of electric charges. Selection of proper stabiliser will govern the stability of NPs and ultimately development of optimised drug delivery system. This review summarises mechanism of physical instability issues likely to be encountered during the development of nanoformulations. It also discusses potential stabilising agents used so far and their mechanism in achieving stable nanosystems.

Endothelin-1 gene variants and levels associate with adaptation to hypobaric hypoxia in high-altitude natives.

High-altitude natives are adapted to hypobaric hypoxia, suggestive of genetic basis of adaptation. Since endothelin-1 (ET-1) is of prime importance in high-altitude disorders in sojourners, we envisaged the role of allelic variants of ET-1 in high-altitude adaptation. Four ET-1 polymorphisms, viz., (CT)(n)-(CA)(n) repeat, -3A/-4A, G2288T, and Lys198Asn, were investigated in 426 highlanders (HLs) and 236 lowlanders (LLs). The plasma ET-1 levels, SBP and BMI were significantly lower in the HLs than those in LLs (p<0.0001). The Longer-repeats (31-45), G allele, Longer-repeats/GG, and Longer-repeats/Lys198Lys combinations were overrepresented in the HLs (p<0.0001, p=0.03, p<0.0001, and p<0.0001, respectively). The Longer-repeats, -3A/-3A, GG and Lys198Lys genotypes associated with significantly lower ET-1 levels in the HLs (p<0.0001, p=0.001, p<0.0001, and p<0.0001, respectively). Combinations of Longer-repeats with -3A/-3A, GG, and Lys198Lys genotypes, and -3A/-3A/Lys198Lys combination revealed association with lower ET-1 levels in the HLs (p<0.001). The study reports over-representation of Longer-repeats, G allele, and wild-type genotype combinations in high-altitude natives. Interaction between these alleles and association with lower ET-1 levels strengthen their association with high-altitude adaptation. Presence of such alleles in sojourners may help in acclimatization.