Cubosomes: Design, Development, and Tumor-Targeted Drug Delivery Applications.

Because of the extraordinary advancements in biomedical nanotechnology over the last few decades, traditional drug delivery systems have been transformed into smart drug delivery systems that respond to stimuli. These well-defined nanoplatforms can boost therapeutic targeting efficacy while reducing the side effects/toxicities of payloads, which are crucial variables for enhancing patient compliance by responding to specific internal or external triggers. Cubosomes are lipid-based nano systems that are analogous to well-known vesicular systems, such as lipo- and niosomes. They could be used as part of a unique drug delivery system that includes hydro-, lipo-, and amphiphilic drug molecules. In this review, we critically analyze the relevant literature on cubosomesregarding theories of cubosomeself-assembly, composition, and manufacturing methods, with an emphasis on tumor-targeted drug delivery applications. Due to the bioadhesive and -compatible nature of cubosome dispersion, this review also focuses on a variety of drug delivery applications, including oral, ophthalmic and transdermal.

Clinical variability of CYP1B1 gene variants in Pakistani primary congenital glaucoma families.

OBJECTIVE: To explore the spectrum of Cytochrome P450 1B1 gene variants and genotype-phenotype correlations in families affected with primary congenital glaucoma. METHODS: The cross-sectional study was performed at the Department of Biotechnology, Lahore College for Women University, Lahore, and the School of Biological Sciences, University of the Punjab, Lahore, Pakistan, from February 2015 to October 2016. Six consanguineous families having individuals affected with primary congenital glaucoma were recruited from different hospitals of the city. Sanger sequencing of coding exon of Cytochrome P450 1B1 gene was performed in order to identify the variants segregating with the disorder. RESULTS: All six families had multiple individuals affected with primary congenital glaucoma. Five out of six families (83%, 5/6) showed CYP1B1 mutations upon Sanger sequencing.All eighteen patients of five families with homozygous Cytochrome P450 1B1 gene variants had different degrees of severity of the phenotypes. Clinical evaluation of the affected members revealed congenital glaucoma with a severe phenotype of corneal oedema, photophobia and corneal scarring. The onset of the phenotype was reported to be congenital but the clinical diagnosis was delayed in four cases since medical help was not sought by the families till much later. CONCLUSIONS: The different degrees of severe phenotypes even in individuals with the same Cytochrome P450 1B1 gene mutation suggested the involvement of modifiers in reducing or increasing the disease severity.

Homozygous p.G61E mutation in a consanguineous Pakistani family with co-existence of juvenile-onset open angle glaucoma and primary congenital glaucoma.

Glaucoma is one of the primary causes of visual impairment and blindness in the world. It is characterized by the damage to the optic nerve head and visual field loss. Variants in CYP1B1 are the most common cause of glaucoma in different world populations. We studied a consanguineous Pakistani family in which three affected individuals had a severe form of glaucoma with members in one generation diagnosed with juvenile-onset open angle glaucoma at 27 years of age, while the members of the next generation were affected with primary congenital glaucoma with onset at birth. Sequencing of CYP1B1 revealed a homozygous transition variant, c.182G>A, p.G61E which co-segregated with the disease phenotype. This variant has been previously reported to cause both recessively and dominantly inherited PCG and JOAG in different populations. However, this reported for the first time in Pakistani PCG and JOAG patients in a homozygous state. This is also the first ever report of a CYP1B1 variant segregating in a consanguineous family with co-existence of JOAG and PCG in two subsequent generations. This observation of different phenotypes due to an identical mutation suggests that primary congenital glaucoma and juvenile-onset open angle glaucoma can both be caused by homozygosity for the same mutation. It also indicates the reduced penetrance of the variant in those affected due to p.G61E mutation and further implies that modifiers have a role in controlling the time of onset of the disorder.