Ultrasound-Triggered Controlled Drug Delivery and Biosensing Using Silica Nanotubes

Silica nanotubes (SNTs) have been demonstrated here as a versatile host for controlled drug delivery and biosensing. The sol-gel template synthesized SNTs have a slow rate of drug release. Application of an external stimulus in the form of ultrasound to or chemical functionalization of synthesized SNT results in higher yield of drug release as well as yield of drug release varying linearly with time. In case of controlled drug delivery triggered by ultrasound, drug yield as function of time is found to be heavily dependent on the ultrasound impulse protocol. Impulses of shorter duration (similar to 0.5 min) and shorter time intervals between successive impulses resulted in higher drug yields. Confinement of hemoglobin (Hb) inside nanometer sized channels of SNT does not have any detrimental effect on the native protein structure and function. Observance of significant enhancement in direct electron transfer of Hb makes the SNTs also promising for application in biosensors

Small-Molecule Modulation of Lipid-Dependent Cellular Processes against Cancer: Fats on the Gunpoint

Lipid cell membrane composed of various distinct lipids and proteins act as a platform to assemble various signaling complexes regulating innumerous cellular processes which are strongly downregulated or altered in cancer cells emphasizing the still-underestimated critical function of lipid biomolecules in cancer initiation and progression. In this review, we outline the current understanding of how membrane lipids act as signaling hot spots by generating distinct membrane microdomains called rafts to initiate various cellular processes and their modulation in cancer phenotypes. We elucidate tangible drug targets and pathways all amenable to small-molecule perturbation. Ranging from targeting membrane rafts organization/reorganization to rewiring lipid metabolism and lipid sorting in cancer, the work summarized here represents critical intervention points being attempted for lipid-based anticancer therapy and future directions

Influence of surface chemistry of mesoporous alumina with wide pore distribution on controlled drug release

The crucial role of the drug carrier surface chemical moeities on the uptake and in vitro release of drug is discussed here in a systematic manner. Mesoporous alumina with a wide pore size distribution (2-7 nm) functionalized with various hydrophilic and hydrophobic surface chemical groups was employed as the carrier for delivery of the model drug ibuprofen. Surface functionalization with hydrophobic groups resulted in low degree of drug loading (approximately 20%) and fast rate of release (85% over a period of 5 h) whereas hydrophilic groups resulted in a significantly higher drug payloads (21%-45%) and slower rate of release (12%-40% over a period of 5 h). Depending on the chemical moiety, the diffusion controlled (proportional to time(-0.5)) drug release was additionally observed to be dependent on the mode of arrangement of the functional groups on the alumina surface as well as on the pore characteristics of the matrix. For all mesoporous alumina systems the drug dosages were far lower than the maximum recommended therapeutic dosages (MRTD) for oral delivery. We envisage that the present study would aid in the design of delivery systems capable of sustained release of multiple drugs

Structure and Function of Hemoglobin Confined Inside Silica Nanotubes

Investigations on the structure and function of hemoglobin (Hb) confined inside sol-gel template synthesized silica nanotubes (SNTs) have been discussed here. Immobilization of hemoglobin inside SNTs resulted in the enhancement of direct electron transfer during an electrochemical reaction. Extent of influence of nanoconfinement on protein activity is further probed via ligand binding and thermal stability studies. Electrochemical investigations show reversible binding of n-donor liquid ligands, such as pyridine and its derivatives, and predictive variation in their redox potentials suggests an absence of any adverse effect on the structure and function of Hb confined inside nanometer-sized channels of SNTs. Immobilization also resulted in enhanced thermal stability of Hb. The melting or denaturation temperature of Hb immobilized inside SNTs increase by approximately 4 degrees C as compared with that of free Hb in solution

Effects of surface acidity and pore size of mesoporous alumina on degree of loading and controlled release of ibuprofen

We report here the simultaneous influence of surface functionality and pore size of mesoporous alumina (Al2O3) host on ibuprofen (IBU) loading and release. Variation in surface acidity is due to the changes in surface density of OH group. Most importantly density variation of OH did not affect the morphological parameters such as surface area, pore size and distribution. Through a novel synthesis method, high degree of IBU loading was possible into Al2O3(X) (X: acidic (A), basic (B), neutral (N)). IBU content as high as 26% (w/w Al2O3(A)–IBU) could be impregnated into Al2O3(A) while Al2O3(B) had the lowest IBU content of 22% (w/w Al2O3(A)–IBU). The in vitro IBU release kinetics are heavily influenced by the varying Al2O3 surface acidity. Systematic observation showed release of IBU from Al2O3(B) taking place at a significantly faster rate compared to Al2O3(A). The release kinetics was also observed to be dependent on concentration ratio of Al2O3 to IBU and pH of the release medium. We envisage that the present study will be beneficial for design of better mesoporous materials for controlled drug delivery systems

Comparative study of different doses of clonidine as an adjuvant with isobaric levobupivacaine for spinal anaesthesia in patients undergoing caesarean section

Background: Various techniques of central neuraxial blockade have been tried and successfully used for caesarean section surgeries. Nowadays it is must and essential to know the possible effective dose of clonidine to overcome its known side effect like bradycardia, hypotension and sedation for better outcome of mother as well as foetus in lower segment caesarean section. We have conducted such study to compare different doses of clonidine as an adjuvant to intrathecal isobaric levobupivacaine. The plain levobupivacaine has been shown to truly isobaric with respect to CSF of pregnant women and this property got advantage over hyperbaric bupivacaine in its predictable spread. Materials and Methods: There were about 90 cases of emergency caesarean section of more than 37 weeks gestation with ASA physical status class 2 under spinal anaesthesia were randomly divided into three groups of 30 patients each. In all groups we assessed onset, two segment regression and requirement of analgesic in post-operative period, level of motor block by modified bromage scale [Table 1] and sedation by Campbell sedation score [Table 2]. Maternal and foetal hemodynamic was monitored as well. Group A (n = 30) 10 mg of 0.5% (2 ml) isobaric levobupivacaine + 15 mcg clonidine (0.5 ml). Group B (n = 30) 10 mg of 0.5% (2 ml) isobaric levobupivacaine + 30 mcg clonidine (0.5 ml). Group C (n = 30) 10 mg of 0.5% (2 ml) isobaric levobupivacaine + 45 mcg clonidine (0.5 ml). Normal saline was used to make volume of clonidine upto 0.5 ml. Result: Onset of sensory block was highest in group A with significant difference (P value <0.0001) in all three groups. Two segment regression time (in minutes) was highest in group C with significant difference (P value <0.0001) in all three groups. There was fall in systolic blood pressure (SBP) <80% of baseline was found in 0 (0.00%), 10 (33.33%) and 22 (73.33%) patients in group A, B and C respectively while fall in HR <80% of baseline was found in 0 (0.00%), 1 (3.33%) and 19 (63.33%) patients. Sedation score was 1 in 30 (100%) patients in group A, it was 1 in 10 (33.33%), 2 in 20 (66.67%) in group B while it was 1 in 5 (16.77%), 2 in 10 (33.33%) and 3 in 15 (50%) patients in group C. Conclusion: Spinal anaesthesia performed with isobaric 0.5% levobupivacaine with 30 mcg clonidine (Group B) provides better haemodynamic stability, early onset of sensory and motor blockade, decreased requirement of post-operative analgesia