Preparation, characterization and in vitro evaluation of insulin-PHBV nanoparticles / alginate hydrogel composite system for prolonged delivery of insulin.

PURPOSE: In the present study, biodegradable poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) nanoparticles (NPs) containing insulin were loaded in sodium alginate/jeffamine (ALG/jeff) hydrogel for prolonged delivery of insulin. The main aim of this work was to fabricate an efficient insulin delivery system to improve patient adherence by decreasing the repetition of injections. METHODS: Swelling and morphological properties and crosslinking efficiency of ALG/jeff hydrogel were assessed. The composite hydrogel was prepared by adding PHBV NPs to ALG/jeff hydrogel concurrently with crosslinking process. The morphology and loading capacity of composite hydrogel were analyzed. RESULTS: Circular dichroism measurement demonstrated that insulin remains stable following fabrication process. The release profile exhibited 54.6% insulin release from composite hydrogel within 31 days with minor initial burst release equated to nanoparticles and hydrogels. MTT cell viability analysis was performed by applying L-929 cell line and no cytotoxic effect was observed. CONCLUSIONS: Favorable results clearly introduced fabricated composite hydrogel as an excellent candidate for drug delivery systems and also paves the route for prolonged delivery systems of other proteins.

Chitosan as a machine for biomolecule delivery: A review.

The major role of biomolecules in treatment of different diseases has been proven by several studies. However, the main drawback in successful treatment by these molecules is designing of efficient delivery systems to fulfill all of the delivery purposes. In this regard, many polymeric vehicles have been introduced for protecting and delivery of biomolecules to the target site. Chitosan as a unique biopolymer with special properties has been widely used for biomolecule delivery. Several research groups have focused on developing and applying of chitosan as a versatile machine in biomolecule delivery. In this review the unique properties of chitosan have been discussed at first and then its application as a delivery machine for different types of biomolecules include protein and peptides, nucleic acids and vaccines has been considered. Furthermore, the targeting approach by conjugation of various ligands to the chitosan and also the current challenges for development of chitosan vehicles will be discussed for biomolecule delivery.

Fabrication, Optimization, and In Vitro and In Vivo Characterization of Intra-vitreal Implant of Budesonide Generally Made of PHBV.

Drug delivery to vitreous in comparison with drug delivery to the other parts of the eye is complicated and challenging due to the existence of various anatomical and physiological barriers. Developing injectable intra-vitreal implant could be beneficial in this regard. Herein, poly(hydroxybutyrate-co-valerate) (PHBV) implants were fabricated and optimized using response surface method for budesonide (BZ) delivery. The acquired implants were characterized in regard to the stability of the ingredients during fabrication process, drug loading amount, and drug release pattern (in PBS-HA-A and in vitreous medium). According to this research and statistical analysis performed, first HV% (hydroxyvalerate) then molecular weight and ratio of PEG as pore former affect respectively release rate and burst strength of BZ with different coefficients. Drug release profile in rabbit eye correlated well with that of in vitro (R2 = 0.9861, p Ë‚ 0.0001). No significant changes were seen in ERG waves, intraocular pressure, and histological studies during the in vivo part of the project. Using 8% HV, 20% PEG/PHBV, and higher molecular weight PEG (i.e., 6000), the optimum formulation was achieved. Toxicity and biocompatibility of the optimized formulation, which were evaluated in vivo, indicated the suitability of design implant for intra-vitreal BZ delivery. Grapical abstract.

Novel chitosan based nanoparticles as gene delivery systems to cancerous and noncancerous cells.

The present study aimed to investigate in vitro DNA transfection efficiency of three novel chitosan derivatives: thiolated trimethyl chitosan (TMC-Cys), methylated 4-N,N dimethyl aminobenzyl N,O carboxymethyl chitosan(MABCC) and thiolated trimethyl aminobenzyl chitosan(MABC-Cys). After polymer synthesis and characterization, nanoparticles were prepared using these polymers and their size, zeta potential and DNA condensing ability were measured. After that, cytotoxicity and transfection efficiency of nanocomplexes were carried out in three different cells. The results showed that all polymers could condense DNA plasmid strongly from N/P 2 and nanocomplexes had eligible sizes and zeta potentials. Moreover, the nanocomplexes had negligible cytotoxicity and MABC-Cys was the most effective vehicle for gene delivery in HEK-293T cells. In the two other cell lines, SKOV-3 and MCF-7, TMC-Cys exhibited the highest transfection efficiency. This study indicated that chemical structure of these novel chitosan derivatives in the interaction with the cell type can lead to successful gene delivery.

Targeted poly (L-γ-glutamyl glutamine) nanoparticles of docetaxel against folate over-expressed breast cancer cells.

A novel folate (FA) conjugated poly(l-γ-glutamyl glutamine) (PGG) nanoparticle loaded with docetaxel (DTX) was prepared to take advantage of both targeted drug delivery in breast cancer and reducing the overall side effects due to the adjuvant free formulation in comparison with Taxotere(®). Nanoprecipitation method was employed to prepare nanoparticles (NPs). The chemical structure of PGG synthesized polymers and PGG-FA conjugates and polymeric nanoparticles were characterized by H NMR, FTIR spectroscopy, field emission scanning electron microscopy, and laser scanning confocal microscopy. The average size of optimized nanoparticles with the aid of Box-Behnken experimental design was 131.96 ± 5.34(nm) with polydispersity of 0.089 ± 0.019, zeta potential of -25.8 ± 2.21(mV), and entrapment efficiency of 67.83 ± 3.29(%). In vitro cytotoxicity of the designed NPs was investigated by MTT assay against three chosen cell lines of MCF7, 4T1, and A549 based on their folate receptor expression capacity and was compared with Taxotere(®). Moreover, PGG-FOL NPs were loaded with 6-coumarin for cellular uptake investigation. In order to assess the antitumor efficacy and biodistribution of targeted NPs, 4T1 murine breast tumors were established on the balb/c mice and in vivo studies were performed. The obtained results showed that the novel designed system was highly effective against tumor cells and successfully localized in the tumor site.

Stability studies of chitosan-DNA-FAP-B nanoparticles for gene delivery to lung epithelial cells.

A successful gene delivery system requires efficiency and stability during storage. Stability studies are imperative for nanomedicines containing biotechnological products such as plasmids and targeting peptides. Chitosan-DNA-FAP-B nanoparticles are novel non-viral vectors for specific gene delivery to the lung epithelial cells. In this study, the storage stability of chitosan-DNA-FAP-B nanoparticles at -20, 5 and 24 °C was examined. Size, zeta potential and transfection efficiency of these nano-particles in storage were also evaluated. Stability studies showed that chitosan-DNA-FAP-B nanoparticles were stable after 1 month when stored at -20 °C and retained their initial size, zeta potential and transfection efficiency. However, their stability was not desirable at 5 and 24 °C. Based on these results, it can be concluded that chitosan-DNA-FAP-B nanoparticles can be a promising candidate for gene delivery to lung epithelial cells with good storage stability at -20 °C during 1 month.