Gold nanorod embedded reduction responsive block copolymer micelle-triggered drug delivery combined with photothermal ablation for targeted cancer therapy.

BACKGROUND: Gold nanorods, by virtue of surface plasmon resonance, convert incident light energy (NIR) into heat energy which induces hyperthermia. We designed unique, multifunctional, gold nanorod embedded block copolymer micelle loaded with GW627368X for targeted drug delivery and photothermal therapy. METHODS: Glutathione responsive diblock co-polymer was synthesized by RAFT process forming self-assembled micelle on gold nanorods prepared by seed mediated method and GW627368X was loaded on to the reduction responsive gold nanorod embedded micelle. Photothermal therapy was administered using cwNIR laser (808nm; 4W/cm2). Efficacy of nanoformulated GW627368X, photothermal therapy and combination of both were evaluated in vitro and in vivo. RESULTS: In response to photothermal treatment, cells undergo regulated, patterned cell death by necroptosis. Combining GW627368X with photothermal treatment using single nanoparticle enhanced therapeutic outcome. In addition, these nanoparticles are effective X-ray CT contrast agents, thus, can help in monitoring treatment. CONCLUSION: Reduction responsive nanorod embedded micelle containing folic acid and lipoic acid when treated on cervical cancer cells or tumour bearing mice, aggregate in and around cancer cells. Due to high glutathione concentration, micelles degrade releasing drug which binds surface receptors inducing apoptosis. When incident with 808nm cwNIR lasers, gold nanorods bring about photothermal effect leading to hyperthermic cell death by necroptosis. Combination of the two modalities enhances therapeutic efficacy by inducing both forms of cell death. GENERAL SIGNIFICANCE: Our proposed treatment strategy achieves photothermal therapy and targeted drug delivery simultaneously. It can prove useful in overcoming general toxicities associated with chemotherapeutics and intrinsic/acquired resistance to chemo and radiotherapy.

Spontaneous vesicle formation by γ-aminobutyric acid derived steroidal surfactant: Curcumin loading, cytotoxicity and cellular uptake studies.

Cholesterol (Chol) is a ubiquitous steroidal component of cell membrane and is known to modulate the packing of phospholipids within the bilayer. Thus, Chol has been frequently used in the formulation and study of artificial "model membranes" like vesicles and liposomes. In this work, we have developed a novel anionic surfactant by conjugating two biomolecules, cholesterol and γ-aminobutyric acid via a urethane linkage. We have studied its physicochemical behavior in aqueous buffer. The surfactant has been shown to spontaneously form small unilamellar vesicles above a very low critical concentration in aqueous neutral buffer at room temperature. The vesicle phase was characterized by use of fluorescence probe, transmission electron microscopy and dynamic light scattering (DLS) techniques. The vesicle bilayer was found to be much less polar as well as more viscous compared to the bulk water. The vesicle stability with respect to change of temperature, pH, and ageing time was investigated by fluorescence probe and DLS techniques. The loading efficiency of the vesicles for the hydrophobic drug, curcumin, was determined and its release under physiological condition was studied. The in vitro cellular uptake of curcumin-loaded vesicles to human breast cancer cell line (MDA-MB-231) also was investigated. The MTT assay showed that the surfactant was non-cytotoxic up to a relatively high concentration.

Natal and neonatal teeth among cleft lip and palate infants.

OBJECTIVE: Natal/neonatal teeth are reported to be more common among clefts and congenital anomalies. Data exclusively among clefts is sparse. The aim was to evaluate prevalence of natal teeth among cleft lip and palate neonates and review the causes, presentation, associated anomalies, complications and management. MATERIALS AND METHODS: Out of 641operated patients, records of 151 infants with cleft lip and palate with less than three months of age presented to the department of plastic and reconstructive surgery from 2005 to 2011 were reviewed. Out of which 107 were unilateral complete lip and palate (ULCP), 15 bilateral cleft lip and isolated cleft palate constituted 29. RESULTS: Three patients among the studied records showed neonatal teeth. Two had paired central mandibular incisor teeth along with associated other anomalies and one had a single maxillary neonatal tooth. All were present in unilateral cleft lip and none of the bilateral or isolated cleft palate infants showed neonatal teeth. The overall incidence of neonatal teeth was 1.98% and 2.8% in unilateral Cleft lip. CONCLUSION: Our study supports the incidence of 2% natal teeth among UCLP. Involvement of mandibular central incisors in contrast to the notion that maxillary alveolus is more commonly affected suggest that it is not only the anatomical disturbance but also all those possible common multifactorial etiological factors contributing to the congenital anomalies as such. Natal/neonatal teeth are rather under-diagnosed and reported than a rare phenomenon and the prevalence is higher in certain population. Riga-Fede disease unlikely to be seen in clefts with neonatal teeth due to anatomical factors. The extraction of non mobile tooth if necessary can be done during the primary surgery for the cleft lip.