The Use of Polymer Blends in the Treatment of Ocular Diseases.

The eye is an organ with limited drug access due to its anatomical and physiological barriers, and the usual forms of ocular administration are limited in terms of drug penetration, residence time, and bioavailability, as well as low patient compliance. Hence, therapeutic innovations in new drug delivery systems (DDS) have been widely explored since they show numerous advantages over conventional methods, besides delivering the content to the eye without interfering with its normal functioning. Polymers are usually used in DDS and many of them are applicable to ophthalmic use, especially biodegradable ones. Even so, it can be a hard task to find a singular polymer with all the desirable properties to deliver the best performance, and combining two or more polymers in a blend has proven to be more convenient, efficient, and cost-effective. This review was carried out to assess the use of polymer blends as DDS. The search conducted in the databases of Pubmed and Scopus for specific terms revealed that although the physical combination of polymers is largely applied, the term polymer blend still has low compliance.

Field-flow fractionation for molecular-interaction studies of labile and complex systems: A critical review.

Asymmetrical flow field-flow fractionation (AF4) has attracted considerable attention as a size-based separation technique, due to its mild separation conditions, broad working range (from approximately 103 to 109 Da molecular mass or from 1 nm to 1 µm particle diameter), and versatility. AF4 is primarily being used to measure particle size, polydispersity, and physical stability of various systems, such as (bio)-macromolecules and nanoparticles. In comparison with size-exclusion chromatography (packed column), AF4 (open channel) allows separation while preserving labile structures. Monitoring of interactions between different compounds and in very complex matrices is possible. Preservation of the structure and correlation of structural characteristics with activity and functionality can bolster the development of new therapeutic strategies for diseases and new materials with improved properties. In this review, a detailed overview is presented of developments in AF4 for interaction studies between various systems, such as protein-protein, polymer-polymer, nanoparticle-drug, and nanoparticle-protein. The prospects and obstacles for AF4, and other less-commonly used types of FFF, for studying interactions within complex and fragile systems are covered. Coupling AF4 to a variety of detection systems can greatly contribute to the understanding of the interaction/association processes and provide information on the interaction kinetics. This review is intended to provide comprehensive documentation on the types of information (structural, morphological, chemical) on molecular interactions that can be retrieved by AF4.

A novel soluble supramolecular system for sustained rh-GH delivery.

Methoxy-poly(ethylene glycol)s bearing a terminal cholanic moiety (mPEG(5kDa)-cholane, mPEG(10kDa)-cholane and mPEG(20kDa)-cholane) were physically combined with recombinant human growth hormone (rh-GH) to obtain supramolecular assemblies for sustained hormone delivery. The association constants (Ka) calculated by Scatchard analysis of size exclusion chromatography (SEC) data were in the order of 10(5)M(-1). The complete rh-GH association with mPEG(5kDa)-cholane, mPEG(10kDa)-cholane and mPEG(20kDa)-cholane was achieved with 7.5 ± 1.1, 3.9 ± 0.4 and 2.6 ± 0.4 w/w% rh-GH/mPEG-cholane, respectively. Isothermal titration calorimetry (ITC) yielded association constants similar to that calculated by SEC and showed that rh-GH has 21-25 binding sites for mPEG-cholane, regardless the polymer molecular weight. Dialysis studies showed that the mPEG-cholane association strongly delays the protein release; 80-90% of the associated rh-GH was released in 200 h. However, during the first 8h the protein formulations obtained with mPEG(10kDa)-cholane and mPEG(20kDa)-cholane showed a burst release of 8 and 28%, respectively. Circular dichroism (CD) analyses showed that the mPEG(5kDa)-cholane association does not alter the secondary structure of the protein. Furthermore, mPEG(5kDa)-cholane was found to enhance both the enzymatic and physical stability of rh-GH. In vivo pharmacokinetic and pharmacodynamic studies were performed by subcutaneous administration of rh-GH and rh-GH/mPEG(5kDa)-cholane to normal and hypophysectomised rats. The study showed that mPEG(5kDa)-cholane decreases the maximal concentration in the blood but prolongs the body exposure of the protein, which resulted in 55% bioavailability increase. Finally, rh-GH formulated with mPEG(5kDa)-cholane yielded prolonged weight increase of hypophysectomised rats as compared to rh-GH in buffer or formulated with mPEG(5kDa)-OH. After the second administration the weight of the animals treated with rh-GH formulated with mPEG(5kDa)-cholane was about 2 times higher than that obtained with equal dose of non-formulated rh-GH.