Alginate-chitosan Nanoparticles Research Articles

Exploring Endolysin-Loaded Alginate-Chitosan Nanoparticles as Future Remedy for Staphylococcal Infections.

Endolysins are a novel class of antibacterials with proven efficacy in combating various bacterial infections, in vitro and in vivo. LysMR-5, an endolysin derived from phage MR-5, demonstrated high lytic activity in our laboratory against multidrug-resistant S. aureus (MRSA) and S. epidermidis strains. However, endolysin and proteins in general are associated with instability and short in vivo half-life, consequently limiting their usage as pharmaceutical preparation to treat bacterial infections. Nanoencapsulation of endolysins could help to achieve better therapeutic outcome, by protecting the proteins from degradation, providing sustained release, thus could increase their stability, shelf life, and therapeutic efficacy. Hence, in this study, the feasibility of alginate-chitosan nanoparticles (Alg-Chi NPs) to serve as drug delivery platform for LysMR-5 was evaluated. LysMR-5-loaded nanoparticles were prepared by calcium ion-induced pre-gelation of alginate core and its complexation with chitosan. The formation of nanoparticles was confirmed on the basis of DLS, zeta potential, and electron microscopy imaging. The LysMR-5-loaded nanoparticles presented a hydrodynamic diameter of 276.5 ± 42, a PDI of 0.342 ± 0.02, a zeta potential - 25mV, and an entrapment efficiency of 62 ± 3.1%. The potential ionic interaction between alginate, chitosan, and LysMR-5 was investigated by FT-IR and SEM-EDX analysis. Using scanning electron microscopy (SEM) and transmission electron microscopy (TEM), nano-sized particles with characteristic morphology were seen. Different antibacterial assays and SDS-PAGE analysis showed no change in endolysin's structural integrity and bioactivity after entrapment. A direct antibacterial effect of blank Alg-Chi Nps, showing enhanced bactericidal activity upon LysMR-5 loading, was observed against S. aureus. At physiological pH (7.2), the release profile of LysMR-5 from Alg-Chi NPs showed a biphasic release and followed a non-Fickian release mechanism. The biocompatible nature as revealed by cytocompatibility and hemocompatibility studies endorsed their use as drug delivery system for in vivo studies. Collectively, these results demonstrate the potential of Alg-Chi NPs as nano-delivery vehicle for endolysin LysMR-5 and other therapeutic proteins for their use in various biomedical applications.

Evaluation of amygdalin-loaded alginate-chitosan nanoparticles as biocompatible drug delivery carriers for anticancerous efficacy

Amygdalin, despite possessing anticancerous properties, has been viewed as a controversial choice due to the presence of the cyanide group. Here, we synthesise and investigate the potential of alginate–chitosan nanoparticles (ACNPs) as drug delivery agents for amygdalin encapsulation and its delivery to cancer cells. Amygdalin loaded ACNPs were made with both anionic and cationic outer layer to further investigate charge dependency on drug delivery and cytotoxicity. ACNPs encapsulating amygdalin were monodisperse, colloidally stable with ~90% drug encapsulation efficiency and were entirely made from natural materials. The nanoparticles exhibited sustained drug release for a duration of 10 h and significant swelling rates in neutral and slightly acidic environments. The ACNPs successfully adhered to porcine mucin type II when assessed for its mucoadhesion and shown to transmigrate with an average velocity of 1.68 μm/s in uncoated channels, under biomimicked flow conditions. To investigate charge dependency on drug delivery and cytotoxicity, amygdalin loaded ACNPs were made with both anionic and cationic outer layer and assessed. ACNPs demonstrated greater yet sustained anti-cancerous effect on H1299 cell lines in a dose-dependent manner than free amygdalin suggesting greater cellular uptake of the former. In conclusion, biocompatible and biodegradable alginate–chitosan nanoparticles can be used as an effective drug delivery system for sustained and controlled amygdalin release with its improved cytotoxic effect on cancerous cells while protecting normal cells and tissues.

Interfacial Phenomenon Based Biocompatible Alginate-Chitosan Nanoparticles Containing Isoniazid and Pyrazinamide.

Tuberculosis (TB) is one of the major health challenge in the world. The current treatment of TB needs daily administration of combined drug therapy for six or more months. Sometime non-adherence and less bioavailability from current therapy develops multidrug resistance, as a result, high dose requirement and subsequent intolerable toxicity are seen. Therefore, nanotechnology gained special attention as it has potential to improve patient compliance, bioavailability and reduction in dosing frequency. The aim of this study is to fabricate alginate-chitosan nanoparticles (AL-CS NPs) under appropriate conditions using ionic gelation method. The use of natural polymers in nanoparticle fabrication has a vast application due to their biodegradability, biocompatibility and nontoxic nature. Ionic gelation method involves the interaction between macromolecules with opposite charged ionizable groups forming polyelectrolyte complex. Hence, it is rational to formulate natural polymerbased sustained release nano-particulate matrix to improve patient adherence, reducing dose frequency and drug toxicity. The formulations were based on 32 factorial designs. Nanoparticles of combined drug (Isoniazid- INH and Pyrazinamide-PYZ) were fabricated using natural polymer. Formulation process involved the use of pregelated sodium alginate followed by ionic gelation with chitosan. Pregelation of sodium alginate included calcium chloride. The effects of sodium alginate concentration and chitosan concentration on particle size, zeta potential, entrapment efficiency and in vitro drug release were studied. Optimized Batch-3s showed particle size 539.7 ± 2.33 nm, zeta potential -26.4 ± 0.55 mV, and entrapment efficiency is 70.21 ± 0.24% and 73.45 ± 0.21% of INH and PYZ, respectively. Dissolution release study of Batch-3s in 7.4 pH phosphate buffer exhibited the initial burst of 5.04 ±0.45% and 19.68 ± 0.87% at 0.25 hrs followed by slow, sustained release of drug 74.53 ± 2.53 and 57.87 ± 2.04% at 10 hrs of INH and PYZ, respectively. It concluded that chitosan (CS) and sodium alginate (AL) concentration are rate-limiting factors in formulation development. Natural polymer based combined drug nano-particulate system could be an innovative and optimistic approach in the treatment of TB.

Optimization and characterization of nisin-loaded alginate-chitosan nanoparticles with antimicrobial activity in lean beef

Nanoencapsulation may improve antimicrobial activity of nisin when applied on food systems such as lean beef. Nisin-loaded nanoparticles were prepared by alginate ionic gelation and further complexation with chitosan. A 3-factor, 3-level Box-Behnken experimental design and response surface methodology were used to optimize the formulation. Nanoparticles had an encapsulation efficiency of 36.1 ± 0.6%, a z-average of 66.4 ± 8.9 nm and a zeta potential of −31.7 ± 2.6 mV. Transmission electron microscopy and atomic force microscopy observations confirmed particle size found by dynamic light scattering. Also, Raman spectroscopy analyses and zeta potential measurements showed ionic interactions between nisin and alginate. In vitro assessment of inhibition of Listeria monocytogenes growth at 4 °C indicated sustained antimicrobial activity of nisin-loaded nanoparticles for 21 days. Furthermore, encapsulated nisin was able to inhibit L. monocytogenes growth in vacuum-sealed, refrigerated beef samples for 10 days when applied at 400 IU/g and for 24 days when applied at 800 IU/g, while free nisin controlled microbial growth for only 4 and 17 days respectively. In sum, we describe the application of experimental design tools to produce nisin-loaded nanoparticles that may be used in the food industry to control microbial growth and hence extend the shelf-life of lean beef.

FORMULATION, OPTIMIZATION, AND CHARACTERIZATION OF BIOCOMPATIBLE INHALABLE D-CYCLOSERINE-LOADED ALGINATE-CHITOSAN NANOPARTICLES FOR PULMONARY DRUG DELIVERY

<p>ABSTRACT<br />Objective: To prepare Nanoparticulate dosage form having improved drug bioavailability and reduced dosing frequency of antitubercular drugs<br />which will helps in improving patient compliance in the treatment of multi-drug resistant tuberculosis (MDR-TB).<br />Methods: Ionotropic gelation method was used to prepare D-cycloserine (D-CS)-loaded alginate-chitosan nanoparticles, and the particles are<br />characterized by their particle size and morphology using particle size analyzer and scanning electron microscopy (SEM). X-ray diffraction (XRD),<br />differential scanning calorimetry (DSC), and Fourier-transformed infrared (FTIR) studies were used to determine drug-polymer interactions and drug<br />entrapment. Entrapment efficiency, drug loading (DL), particle size, and zeta potential of nanoparticles were also studied. The 2<br /> factorial designs of<br />experiments by Design-Expert<br />®<br /> V9 were used to optimize the particle size and entrapment efficiency of nanoparticles.<br />Results: The optimized batch had shown the entrapment efficiency of 98.10±0.24% and DL of 69.32±0.44% with particle size and zeta potential<br />as 344±5 nm and −42±11.40 mV, respectively. DSC, FTIR, and XRD studies confirmed the drug entrapment within nanoparticle matrix. SEM results<br />showed spherical-shaped particles. Sustained release of drug from the nanoparticles was observed for 24 hrs period. Respirable fraction up to<br />52.37±0.7% demonstrates the formulation suitability for deep lung delivery. Lung inflammatory study showed a less inflammatory response.<br />Conclusion: Ionotropic gelation method can be used to prepare biocompatible particles with a high entrapment efficiency, DL, optimum particle size,<br />and controlled release characteristics, which can serve as a convenient delivery system for D-CS and could be a potential alternative to the existing<br />conventional therapy in MDR-TB.<br />Keywords: Nanoparticles, Alginate, Chitosan, Inhalation, Sustained release, Tuberculosis.<br />3</p>