Development and optimization of a novel PLGA-Levan based drug delivery system for curcumin, using a quality-by-design approach.

This study aimed to develop a PLGA, Levan-based drug delivery system (DDS) of Curcumin using a quality-by-design (QbD) approach to reveal how formulation parameters affect the critical quality attributes (CQAs) of this DDS and to present an optimal design. First, a risk assessment was conducted to determine the impact of various process parameters on the CQAs of the DDS (i.e., average particle size, ZP, encapsulation efficiency and polydispersity index). Plackett-Burman design revealed that potential risk factors were Levan molecular weight, PLGA amount and acetone amount. Then, the optimization of the DDS was achieved through a Box-Behnken Design. The optimum formulation was prepared using low molecular weight Levan (134 kDa), 51.51 mg PLGA and 10 ml acetone. The model was validated and the optimized formulation was further characterized using different physic-chemical methods. The study resulted in the most stable NP with a spherical and uniform shape and physical stability tests indicated its stability for at least 60 days at room temperature. In conclusion, this study was an effort for developing a DDS which solubilizes Curcumin in clinically applicable concentrations.

Sugar Based Biopolymers in Nanomedicine; New Emerging Era for Cancer Imaging and Therapy.

Since last decade, sugar based biopolymers are recognized in nanomedicine as promising materials for cancer imaging and therapy. Their durable, biocompatible and adhesive properties enable the fine tuning of their molecular weights (MW) and their miscellaneous nature makes the molecules acquire various conformations. These in turn provide effective endocytosis by cancer cell membranes that have already been programmed for internalization of different kinds of sugars. Therefore, biocompatible sugar based nanoparticles (SBNPs) are suitable for both cell-selective delivery of drugs and imaging through the human body. Recently, well known sugar-based markers have displayed superior performance to overcome tumor metastasis. Thereby, targeting strategies for cancer cells have been broadened to sugar-based markers as noticed in various clinic phases. In these studies, biopolymers such as chitosan, hyaluronic acid, mannan, dextran, levan, pectin, cyclodextrin, chondroitin sulphate, alginates, amylose and heparin are chemically functionalized and structurally designed as new biocompatible nanoparticles (NPs). The future cancer treatment strategies will mainly comprise of these multifunctional sugar based nanoparticles which combine the therapeutic agents with imaging technologies with the aim of rapid monitoring response to therapies. While each individual imaging and treatment step requires a long time period in effective treatment of diseases, these multifunctional sugar based nanoparticles will have the advantage of rapid detection, right drug efficiency evaluation and immediate interfere opportunity to some important diseases, especially rapidly progressing cancers. In this article, we evaluated synthesis, characterization and applications of main sugar based biopolymers and discussed their great promise in nano-formulations for cancer imaging and therapy. However much should be done and optimized prior to clinical applications of these nano-formulations for an efficient drug treatment without overall toxicity for getting most effective clinical results.

Comprehensive characterization of chitosan/PEO/levan ternary blend films.

Ternary blend films of chitosan, PEO (300,000) and levan were prepared by solution casting method and their phase behavior, miscibility, thermal and mechanical properties as well as their surface energy and morphology were characterized by different techniques. FT-IR analyses of blend films indicated intermolecular hydrogen bonding between blend components. Thermal and XRD analysis showed that chitosan and levan suppressed the crystallinity of PEO up to nearly 25% of PEO content in the blend, which resulted in more amorphous film structures at higher PEO/(chitosan+levan) ratios. At more than 30% of PEO concentration, contact angle (CA) measurements showed a surface enrichment of PEO whereas at lower PEO concentrations, chitosan and levan were enriched on the surfaces leading to more amorphous and homogenous surfaces. This result was further confirmed by atomic force microscopy (AFM) images. Cell proliferation and viability assay established the high biocompatibility of the blend films.

Controlled release of 5-aminosalicylicacid from chitosan based pH and temperature sensitive hydrogels.

A series of temperature and pH responsive hydrogels based on chitosan and poly(N-isopropyl acrylamide) (PNIPA) was prepared by redox polymerization. Effect of the composition on swelling behavior of the hydrogels and the release of 5-aminosaylcilic acid (5-ASA) at different temperatures and pHs have been investigated. Ammonium persulphate and TEMED were used as a redox pair at room temperature. As a cross linker, methacrylated chitosan was synthesized through the reaction of chitosan with glycidyl methacrylate (GMA). Introduction of the cross-linker provided the hydrogels with pH and temperature sensitivities. The phase transition temperatures of the hydrogels were determined by derivative differential scanning calorimeter (DDSC). Their phase transition temperatures were increased by chitosan content. Swelling behaviors and the release of 5-ASA varied significantly with pH, temperature and the gel composition. The release of 5-ASA from the hydrogels was followed by UV-Vis and fluorescence spectroscopy.