Poly (lactic-co-glycolic acid) has received much academic attention for developing nanotherapeutics and FDA has approved it for several applications. An important parameter that dictates the bioavailability and hence the biological effect of the drug is drug release from its delivering system. This study offers a comparative mathematical analysis of drug release from Poly (lactic-co-glycolic acid)-based nanoparticles to suggest a general model explaining multi-mechanistic release they provide. Eight release models, zero order, first order, Higuchi, Hixson-Crowell, the square root of mass, the three-second root of mass, Weibull and Korsmeyer-Peppas, as well as the second degree polynomial equation were applied to 60 data sets. The models analysed regarding several types of errors, regression parameters and average Akaike information criterion. Most of the data sets present the highest R2, the lowest overall error and AIC for the Weibull model. Weibull model with the mean AIC = -36.37 and mean OE = 7.24 and the highest NE less than 5, 10, 15 and 20 % in most of the cases best fits the release data from various PLGA-based drug delivery systems that are studied. Weibull model seems to show enough flexibility to describe various release patterns PLGA provides.

Pegylation, generally described as the molecular attachment of polyethylene glycols (PEGs) with different molecular weights to active drug molecules or surface treatment of drug-bearing particles with PEGs, is one of the most promising and extensively studied strategies with the goal of improving the pharmacokinetic behavior of the therapeutic drugs. A variety of PEGs, both linear and branched, with different molecular weights have been exploited successfully for use in this procedure in the form of reactive PEG species. Both reversible and irreversible PEG-drug conjugates have been prepared with relative advantages/disadvantages. The main pharmacokinetic outcomes of pegylation are summarized as changes occurring in overall circulation life-span, tissue distribution pattern, and elimination pathway of the parent drug/particle. Based on these favorable pharmacokinetic consequences leading to desired pharmacodynamic outcomes, a variety of proteins/peptides as well as small molecule drugs have been pegylated and evaluated successfully. Also a number of corresponding products have been approved by the U.S. FDA for specific clinical indications and some others are underway. In this article, the chemistry, rationale, strategies, pharmacokinetic outcomes, and therapeutic possibilities of pegylated drugs are reviewed with pharmacokinetic aspects presented with more details.

Alzheimer’s disease (AD) is one of the most common neurodegenerative diseases and is caused by accumulation of amyloid-β (Aβ) peptide and is associated with neurological abnormalities in learning and memory. The protective role of curcumin on nerve cells, along with a potent antioxidant and free radical scavenging activity, has been widely studied. However, its low bioavailability and limited transport ability across the blood-brain barrier are two major drawbacks of its application in the treatment of different neurodegenerative diseases. The present study was designed to improve the effectiveness of curcumin in the treatment of Aβ-induced cognitive deficiencies in a rat model of AD by loading it into nanostructured lipid carriers (NLCs). The accumulation rate of curcumin (505.76±38.4 ng/g ^–1 h) in rat brain, as well as its serum levels, were significantly increased by using curcumin-loaded NLCs. The effective role of NLCs for brain delivery of curcumin was confirmed by reduced oxidative stress parameters (ROS formation, lipid peroxidation, and ADP/ATP ratio) in the hippocampal tissue and improvement of spatial memory. Also, histopathological studies revealed the potential of Cur–NLCs in decreasing the hallmarks of Aβ in AD in the animal model. The result of studying the neuroprotective potential of Cur-NLC in both pre-treatment and treatment modes showed that loading curcumin in NLCs is an effective strategy for increasing curcumin delivery to the brain and reducing Aβ-induced neurological abnormalities and memory defects and that it can be the basis for further studies in the area of AD prevention and treatment.