36 research outputs found
Development and validation of novel ultraviolet spectrophotometric method for estimation of antileishmanial drug buparvaquone
A novel, simple, accurate, precise, economical and reliable ultraviolet spectrophotometric method has been developed for the estimation of buparvaquone in bulk and in pharmaceutical dosage form. The drug shows maximum absorption at 251 nm by using acetonitrile as solvent. The method was validated as stated in International Council for Harmonisation Q2 (R1) guidelines. It obeys Beer's law in the concentration range of 2-20 ”g/ml with correlation coefficient of 0.998. The drug shows great accuracy close to 100 %. The method was found to be robust and precise as the relative standard deviation are less than 2 %. Limit of detection and limit of quantitation were found to be 0.60 ”g/ml and 1.83 ”g/ml respectively. From the results of specificity, the drug was found to be more degraded under alkaline, oxidative and photolytic conditions. The proposed method can be employed for the reliable quantification of buparvaquone in bulk and routine analysis of pharmaceutical formulations
Lomustine Nanoparticles Enable Both Bone Marrow Sparing and High Brain Drug Levels â A Strategy for Brain Cancer Treatments
Purpose The blood brain barrier compromises glioblastoma chemotherapy. However high blood concentrations of lipophilic, alkylating drugs result in brain uptake, but cause myelosuppression. We hypothesised that nanoparticles could achieve therapeutic brain concentrations without dose-limiting myelosuppression. Methods Mice were dosed with either intravenous lomustine Molecular Envelope Technology (MET) nanoparticles (13 mg kg-1) or ethanolic lomustine (6.5 mg kg-1) and tissues analysed. Efficacy was assessed in an orthotopic U-87 MG glioblastoma model, following intravenous MET lomustine (daily 13 mg kg-1) or ethanolic lomustine (daily 1.2 mg kg-1 - the highest repeated dose possible). Myelosuppression and MET particle macrophage uptake were also investigated. Results The MET formulation resulted in modest brain targeting (brain/ bone AUC0-4h ratios for MET and ethanolic lomustine = 0.90 and 0.53 respectively and brain/ liver AUC0-4h ratios for MET and ethanolic lomustine = 0.24 and 0.15 respectively). The MET formulation significantly increased mice (U-87 MG tumours) survival times; with MET lomustine, ethanolic lomustine and untreated mean survival times of 33.2, 22.5 and 21.3 days respectively and there were no material treatment-related differences in blood and femoral cell counts. Macrophage uptake is slower for MET nanoparticles than for liposomes. Conclusions Particulate drug formulations improved brain tumour therapy without major bone marrow toxicity
Oral particle uptake and organ targeting drives the activity of amphotericin B nanoparticles
There are very few drug delivery
systems that target key organs
via the oral route, as oral delivery advances normally address gastrointestinal
drug dissolution, permeation, and stability. Here we introduce a nanomedicine
in which nanoparticles, while also protecting the drug from gastric
degradation, are taken up by the gastrointestinal epithelia and transported
to the lung, liver, and spleen, thus selectively enhancing drug bioavailability
in these target organs and diminishing kidney exposure (relevant to
nephrotoxic drugs). Our work demonstrates, for the first time, that
oral particle uptake and translocation to specific organs may be used
to achieve a beneficial therapeutic response. We have illustrated
this using amphotericin B, a nephrotoxic drug encapsulated within <i>N</i>-palmitoyl-<i>N</i>-methyl-<i>N</i>,<i>N</i>-dimethyl-<i>N</i>,<i>N</i>,<i>N</i>-trimethyl-6-<i>O</i>-glycol chitosan
(GCPQ) nanoparticles, and have evidenced our approach in three separate
disease states (visceral leishmaniasis, candidiasis, and aspergillosis)
using industry standard models of the disease in small animals. The
oral bioavailability of AmB-GCPQ nanoparticles is 24%. In all disease
models, AmB-GCPQ nanoparticles show comparable efficacy to parenteral
liposomal AmB (AmBisome). Our work thus paves the way for others to
use nanoparticles to achieve a specific targeted delivery of drug
to key organs via the oral route. This is especially important for
drugs with a narrow therapeutic index
3D printing technologies in personalized medicine, nanomedicines, and biopharmaceuticals
3D printing technologies enable medicine customization adapted to patients' needs. There are several 3D printing techniques available, but majority of dosage forms and medical devices are printed using nozzle-based extrusion, laser-writing systems, and powder binder jetting. 3D printing has been demonstrated for a broad range of applications in development and targeting solid, semi-solid and locally applied or implanted medicines. 3D printed solid dosage forms allow the combination of one or more drugs within the same solid dosage form to improve patient compliance, facilitate deglutition, tailor the release profile, or fabricate new medicines for which no dosage form is available. Sustained release 3D-printed implants, stents and medical devices have been used mainly for joint replacement therapies, medical prostheses, and cardiovascular applications. Locally applied medicines such as wound dressing, microneedles, and medicated contact lenses have also been manufactured using 3D printing techniques. The challenge is to select the 3D printing tech-nique most suitable for each application and the type of pharmaceutical ink that should be devel-oped that possesses the required physicochemical and biological performance. The integration of biopharmaceuticals and nanotechnology-based drugs along with 3D printing ("Nanoprinting") brings printed personalized nanomedicines within the most innovative perspectives for the coming years. Continuous manufacturing through the use of 3D-printed microfluidic chips facilitates their translation into clinical practice
BiochemicalÂÂâ and biophysicalâinduced barriergenesis in the blood brain barrier: a review of barriergenic factors for use in in vitro models
Central nervous system (CNS) pathologies are a prevalent problem in aging populations, creating a need to understand the underlying events in these diseases and develop efficient CNSâtargeting drugs. The importance of the bloodâbrain barrier (BBB) has become evident, acting both as a physical barrier to drug entry into the CNS, and potentially as the cause or aggravator of CNS diseases. The development of a biomimetic BBB in vitro model is required for the understanding of BBBârelated pathologies and in the screening of drugs targeting the CNS. There is currently a great interest in understanding the influence of biochemical and biophysical factors, as these have the potential to greatly improve the barrier function of brain microvascular endothelial cells (BMECs). Recent advances in understanding how these may regulate barriergenesis in BMECs can help promote the development of improved BBB in vitro models, and therefore novel interventional therapies for pathologies related to its disruption. This review provides an overview of specific biochemical and biomechanical cues in the formation of the BBB, with a focus on in vitro models and how these might recapitulate BBB function
Delivery of Peptides to the Blood and Brain after Oral Uptake of Quaternary Ammonium Palmitoyl Glycol Chitosan Nanoparticles
The clinical development of therapeutic peptides has been restricted to peptides for non-CNS diseases and parenteral dosage forms due to the poor permeation of peptides across the gastrointestinal mucosa and the blood-brain barrier. Quaternary ammonium palmitoyl glycol chitosan (GCPQ) nanoparticles facilitate the brain delivery of orally administered peptides such as leucine(5)-enkephalin, and here we examine the mechanism of GCPQ facilitated oral peptide absorption and brain delivery. By analyzing the oral biodistribution of radiolabeled GCPQ nanoparticles, the oral biodistribution of the model peptide leucine(5)-enkephalin and coherent anti-Stokes Raman scattering microscopy tissue images after an oral dose of deuterated GCPQ nanoparticles, we have established a number of facts. Although 85-90% of orally administered GCPQ nanoparticles are not absorbed from the gastrointestinal tract, a peak level of 2-3% of the oral GCPQ dose is detected in the blood 30 min after dosing, and these GCPQ particles appear to transport the peptides to the blood. Additionally, although peptide loaded nanoparticles from low (6 kDa) and high (50 kDa) molecular weight GCPQ are taken up by enterocytes, polymer particles with a polymer molecular weight greater than 6 kDa are required to facilitate peptide delivery to the brain after oral administration. By examining our current and previous data, we conclude that GCPQ particles facilitate oral peptide absorption by protecting the peptide from gastrointestinal degradation, adhering to the mucus to increase the drug gut residence time and transporting GCPQ associated peptide across the enterocytes and to the systemic circulation, enabling the GCPQ stabilized peptide to be transported to the brain. Orally administered GCPQ particles are also circulated from the gastrointestinal tract to the liver and onward to the gall bladder, presumably for final transport back to the gastrointestinal tract.Peer reviewe
Folic acid-modified and functionalized CuS nanocrystal-based nanoparticles for combined tumor chemo- and photothermal therapy
Polymeric Nanoparticles
Self-assembling polymers, which are either amphiphilic block copolymers with hydrophobic and hydrophilic blocks, hydrophilic polymer backbones substituted with hydrophobic units or polymers with a low aqueous solubility, may all be used to prepare aqueous dispersions of polymeric nanoparticles. The amphiphilic variants form polymeric micelles and polymeric bilayer vesicles. The hydrophobic polymers form dense amorphous polymeric particles. Polymeric particles, of whichever nature, may be loaded with hydrophobic and hydrophilic drugs, and the bioavailability of the drug compound is altered by this encapsulation within a polymeric nanoparticle. This simple concept has been exploited heavily to yield enhancements in oral, tumour and brain bioavailability and some of these polymeric nanoparticle formulations have undergone clinical testing and even been commercialised, e.g. the nanoparticle paclitaxel formulation AbraxaneNon peer reviewe