Indeed, our uptake data indicate that LNP typically associate with the membranes in T-cells and this interaction may be responsible for the increased drug effects observed in our system.
While more complex classes of receptor binding kinetics are possible, Eq. 2 illustrates a fundamental principle of PD: as Kd is a constant, it can be seen that increasing drug concentration reduces [ R] and increases [DR], hence increasing drug effect.
Figure 1b shows increasing synergism (CI<1) with increasing drug effects (Fa); at 50% Annexin V-positive cells (Fa=0.5), the calculated CI=0.57 suggested strong synergistic cytotoxicity.
The management of a TB and HIV co-infected individual is challenging because of pill burden [ 8], increased drug adverse effects [ 9], drug interaction [ 10] and the immune reconstitution inflammatory syndrome (IRIS) [ 11].
Unnecessary antibiotic use, however, is associated with increased drug expenditure, side effects and antibiotic resistance.
There was no difference in lapatinib uptake between the baseline and day 8 scans, suggesting no effect of increased drug access by inhibition of the drug efflux proteins by therapeutic doses of lapatinib.
The release rate of drug in the various compartments may also have a modest effect, although increased drug release will be countered by the faster clearance of free drug relative to liposomal drug.
27 As a result, older patients will often have increased drug exposure and consequently increased adverse effects.
As expected, increased drug efflux also had a potent effect on decreasing overall exposure.
When compared with standard administration, drug incorporation into nanoparticles shows a variety of advantages such as high stability, protection of incorporated labile drugs from degradation, controlled and sustained drug release, increased drug therapeutic efficacy, and reduced side effects [3, 4].
