A Comprehensive Review on Novel Lipid-Based Nano Drug Delivery.

Novel drug delivery system opens the doors towards nano/micro formulation strategies to overcome the challenges associated with the poorly soluble and permeable drugs. Lipid based nanoparticles are widely accepted that includes liposomes, niosomes and micelles which are FDA approved. Such lipid based drug delivery allows delivery for natural phytoconstituents, biopharmaceutical classification system (BCS) class II and class IV drugs are effectively delivered to improve its solubility, permeability and bioavailability. The article provides the recent advances and application of lipid based dosage form for improvement of therapeutic efficacy.

Long-term study of functional outcomes of robotic assisted medial UKA using mid-vastus approach in a high-volume centre.

Robotic UKA is one of the recent advancement in surgical management for medial compartment knee osteoarthritis. Over the years, there have been many studies which have showed results of various conventional UKA, high tibial osteotomy and even robotic uka for medial OA of knee all over the world. But still there is very less work on long-term outcome-based analysis of functional outcomes of robotic assisted medial UKA using mid-vastus approach, which was the aim of the study. A total of 680 patients with medial OA knee that were undergone robotic assisted UKA. The study was done at tertiary teaching institute and hospital from November 2016 to October 2022. The assessment of pain, clinical-functional assessment, walking ability, range of motion were assessed by KSS, SF-12 at pre-operatively, mid-term follow-ups and at final follow-up -5.03(± 0.52) years after surgery. 680 patients suited for medial UKA in our study with mean age of 65 ± 10.6 years. Average operating time was 42 ± 4.7 min. The mean postoperative KSS was 93 ± 4.3, the mean SF-12 was 49 ± 9.1, 55 ± 8.7 for PS and MS, respectively. The patient had better KSS and SF-12 when compared pre-operatively and final follow-up (p -0.012 and -9.320, p -0.017 and -7.475, p -0.014 and -5.196, p -0.021 and -7.418, respectively). Complications were also very less. Robotic UKA using mid-vastus approach is effective treatment for medial compartmental OA knee. On short/long-term follow-up of patients, functional and radiological outcomes were good with few complications rates.

Advances in the colon-targeted chitosan based multiunit drug delivery systems for the treatment of inflammatory bowel disease.

Chitosan is the polymer of choice for delivery of the active moieties to the colon due to its cationic nature that enables strong mucosal attachment. Chitosan is explored for formulations such as pellets, beads, microspheres, nanoparticles and drug-polymer conjugates for colon targeting of various therapeutic agents in inflammatory bowel disease (IBD). The major challenge in the colonic delivery of drugs in IBD is altered physiological pH, which can be addressed via chitosan containing multiparticulate drug delivery systems owing to their biodegradability in the colon. Its ionic interaction with anionic polymers forms gastro-resistant multi-unit systems that ensures safe delivery of payloads to the colon. In contrast to commercial grade gastro-resistant polymers, chitosan has GRAS (generally regarded as safe) status that ensures safety for long-term therapy in case of chronic diseases such as IBD. Here, we review in detail essential properties of chitosan and chitosan based multiunit formulations for treatment/mitigation of IBD.

Is There a Lower Size Limit for Superconductivity?

The ultimate lower size limit for superconducting order to exist is set by the "Anderson criterion"-arising from quantum confinement-that appears to be remarkably accurate and universal. We show that carefully grown, phase-pure, nanocrystalline bcc-Ta remains superconducting (with ordering temperature, TC ≈ 0.9 K) down to sizes 40% below the conventional estimate of the Anderson limit of 4.0 nm. Further, both the TC and the critical magnetic field exhibit an unusual, nonmonotonic size dependence, which we explain in terms of a complex interplay of quantum size effects, surface phonon softening, and lattice expansion. A quantitative estimation of TC within first-principles density functional theory shows that even a moderate lattice expansion allows superconductivity in Ta to persist down to sizes much lower than the conventional Anderson limit, which can be traced to anomalous softening of a phonon due to its coupling with electrons. This appears to indicate the possibility of bypassing the Anderson criterion by suitable crystal engineering and obtaining superconductivity at arbitrarily small sizes, an obviously exciting prospect for futuristic quantum technologies. We take a critical look at how the lattice expansion modifies the Anderson limit, an issue of fundamental interest to the study of nanoscale superconductivity.

Preparation, Evaluation and Optimization of Multiparticulate System of Mebendazole for Colon Targeted Drug Delivery by Using Natural Polysaccharides.

PURPOSE: A Multiparticulate system of Mebendazole was developed for colon targeted drug delivery by using natural polysaccharides like Chitosan and Sodium-alginate beads. METHODS: Chitosan microspheres were formulated by using Emulsion crosslinking method using Glutaraldehyde as crosslinking agent. Sodium-alginate beads were formulated by using Calcium chloride as gelling agent. Optimization for Chitosan microspheres was carried out by using 2(3) full factorial design. 3(2) full factorial design was used for the optimization of Sodium-alginate beads. The formulated batches were evaluated for percentage yield, particle size measurement, flow properties, percent entrapment efficiency, Swelling studies. The formulations were subjected to Stability studies and In-vitro release study (with and without rat caecal content). Release kinetics data was subjected to different dissolution models. RESULTS: The formulated batches showed acceptable particle size range as well as excellent flow properties. Entrapment efficiency for optimized batches of Chitosan microspheres and sodium alginate beads was found to be 74.18% and 88.48% respectively. In-vitro release of drug for the optimized batches was found to be increased in presence of rat caecal content. The best-fit models were koresmeyer-peppas for Chitosan microspheres and zero order for sodium-alginate beads. CONCLUSION: Chitosan and Sodium-alginate was used successfully for the formulation of Colon targeted Multiparticulate system.

Development of floating chitosan-xanthan beads for oral controlled release of glipizide.

INTRODUCTION: The aim of the present work was to develop controlled release, floating and mucoadhesive beads of glipizide by using the polyionic complexation technique. Plasma half-life of glipizide being 2-4 h was selected for development of controlled release dosage form. METHODS: Formulation batches were designed by employing chitosan as cationic and xanthan gum as anionic polymers. In vitro drug release was evaluated for the period of 24 h in phosphate buffer pH 7.4. RESULTS: Sustained release of drug was observed in all formulation batches with % drug release ranging from 87.50% to 100.67%, no significant effect on the drug release was observed after varying chitosan to xanthan gum ratio. Encapsulation efficiency was found to be in the range of 79.48 ± 1.10-94.48 ± 1.52. In vitro bioadhesion studies showed that beads had satisfactory bioadhesive strength ranging from 67.11% ± 1.73% to 93.12% ± 1.56%. Buoyancy studies revealed that beads possess comparable floating capacity in the gastric fluids. Swelling kinetics was carried in pH 1.2 and 7.4 buffers. Significant difference (P < 0.05) in swelling kinetics was observed. Drug to polymer interaction was analyzed by Fourier transform infrared spectroscopy and differential scanning calorimetry studies. Scanning electron microscopy studies revealed that formed beads were discrete with rough and wrinkled surfaces. CONCLUSIONS: In conclusion, beads were successfully formed by employing chitosan and xanthan gum and showed to possess sustained release effect. Beads also showed pH dependent swelling kinetics, this property can also be applied for the drugs which are susceptible to the acidic environment in the stomach, and comparable bioadhesive and floating properties were also observed.

Improvement of water solubility and in vitro dissolution rate of aceclofenac by complexation with beta-cyclodextrin and hydroxypropyl-beta-cyclodextrin.

The present study deals with the inclusion complexation of aceclofenac with beta-cyclodextrin by grinding, microwave and spray-drying techniques. A derivative of beta-cyclodextrin, hydroxypropyl-beta-cyclodextrin, was also subjected to the complexation process with aceclofenac by spray-drying technique. The samples were subjected to in-vitro dissolution studies, fourier transform infra-red spectroscopy, differential scanning calorimetry, nuclear magnetic resonance spectroscopy and x-ray diffraction studies. The in-vitro dissolution of aceclofenac-hydroxypropyl-beta-cyclodextrin complex was faster as compared to the aceclofenac- beta-cyclodextrin complex and aceclofenac alone. Spray-dried aceclofenac-beta-cyclodextrin complex were subjected to anti-inflammatory and analgesic activity and showed significant anti-inflammatory and analgesic activity.

Optimal enhancement of immune response.

MOTIVATION: Therapeutic enhancement of innate immune response to microbial attack is addressed as the optimal control of a dynamic system. Interactions between an invading pathogen and the innate immune system are characterized by four non-linear, ordinary differential equations that describe rates of change of pathogen, plasma cell, and antibody concentrations, and of an indicator of organic health. Without therapy, the dynamic model evidences sub-clinical or clinical decay, chronic stabilization, or unrestrained lethal growth of the pathogen; the response pattern depends on the initial concentration of pathogens in the simulated attack. In the model, immune response can be augmented by therapeutic agents that kill the pathogen directly, that stimulate the production of plasma cells or antibodies, or that enhance organ health. A previous paper demonstrated open-loop optimal control solutions that defeat the pathogen and preserve organ health, given initial conditions that otherwise would be lethal (Stengel et al. (2002)). Therapies based on separate and combined application of the agents were derived by minimizing a quadratic cost function that weighted both system response and control usage, providing implicit control over harmful side effects. RESULTS: We demonstrate the ability of neighboring-optimal feedback control to account for a range of unknown initial conditions and persistent input of pathogens by adjusting the therapy to account for perturbations from the nominal-optimal response history. We examine therapies that combine open-loop control of one agent with closed-loop control of another. We show that optimal control theory points the way toward new protocols for treatment and cure of human diseases. CONTACT: stengel@princeton.edu; rghiglia@princeton.edu; nkulkarn@princeton.edu