Key Engineering Materials Vol. 819

Abstract: The aim of this study was to prepare the pectin film-based different types of Eudragit^® polymer blends using glycerine as a plasticizer and to study the mechanical properties of these films. The mixing of polymer mixture was carried out using distilled water as a solvent throughout the experiment. The polymer mixture was poured into Petri dish and transferred to hot air oven for solvent evaporation. The maximum positive force and percentage of elongation at break were found at the range of 63.58-409.94 g and 74.92-145.42%, respectively for pectin film-based Eudragit^® RL 30D polymer blends, 87.12-409.94 g and 74.42-145.42%, respectively for pectin film-based Eudragit^® RS 30D polymer blends, 76.50-409.94 g and 72.68-145.42%, respectively for pectin film-based Eudragit^® NM 30D polymer blends, and 137.12-409.94 g and 44.42-145.42%, respectively for pectin film-based Eudragit^® NE 40D polymer blends. The results indicated that the mechanical properties of the pectin film decreased with inclusion of various types of Eudragit^® (p < 0.05). However, it was found that the pectin film-based different types of Eudragit^® polymer blends has high potential to be used in pharmaceutical applications. Further investigation related to the incorporation of drugs or herbal extracts and the in vitro evaluation are recommended.

Abstract: Bone tissue engineering is an alternative approach to generate bone using biomaterials and cells. Hydroxyapatite (HA) has good biocompatibility, osteoinductivity, and osteoconductivity. However, it has limited utility due to poor mechanical properties and slow degradation rate. To improve mechanical properties and to modify degradation profile, hydroxyapatite was tethered in chitosan (CS) and carboxymethyl cellulose (CMC) complex. Gelatin was incorporated to promote cell attachment and polyvinyl alcohol (PVA) was used to improve mechanical strength of this scaffold. The physico-mechanical and biological properties of these scaffolds were investigated. Fourier transform infrared (FTIR) analysis and X-ray diffraction (XRD) showed the incorporation of hydroxyapatite in polymer matrix. The scaffolds had density, compressive strength, and Young’s modulus in the range of 0.24-0.30 g/cm³, 0.028-0.035 MPa, 0.178-0.560 MPa, respectively. The scaffolds had porosity of 69-91 percent. Higher content of PVA decreased porosity of scaffolds. Scanning electron microscope showed porous microstructure with pore size in the range of 60-183 μm. In vitro test on MC3T3-E1 preosteoblast cells showed negligible cytotoxicity of scaffolds. The data suggested that HA/CS/CMC/gelatin/PVA scaffold has potential applications in bone tissue engineering.

Abstract: A site-specific drug delivery system of anticancer agents has been delveloped to enhance the therapeutic efficacy and reduce toxicity to the normal tissue. Semi-synthetic andrographolide analogue 3A.1 (19-tert-butyldiphenylsilyl-8,17-epoxy andrographolide) is one of the potential natural anticancer compounds against many types of cancer including colorectal cancer cells. However, the clinical applications of this compound are limited because of low water solubility and lack of suitable delivery carriers. This study aimed to increase the aqueous solubility and improve the anticancer efficacy of 3A.1 via active targeting approaches. In this study, 3A.1 was loaded into the polymeric micelles self-assembled from N-naphthyl-N,O-succinyl chitosan (NSC). The micelles were conjugated with folate moiety (Fol-NSC) for targeting to the cancer cells. All of the 3A.1-loaded micelles were prepared by dropping method, and the physicochemical properties (size, charge, morphology, encapsulating efficiency, loading capacity), in vitro release behavior and in vitro anticancer activities against HT29 colorectal cancer cells were investigated. The 3A.1-loaded micelles were successfully formulated by dropping method using NSC or Fol-NSC. The micelles loaded with 40% initial 3A.1 showed the maximum encapsulating efficiency and loading capacity. The micelles were in the nanometer range, having a negative surface charge and a spherical structure. The colon site-specific release of the 3A.1 from the 3A.1-loaded micelles was obtained. The release of 3A.1 from the Fol-NSC micelles was slower than that from the NSC micelles. Moreover, the Fol-NSC micelles exhibited superior anticancer efficacy than that of the NSC micelles and free 3A.1. In conclusions, the 3A.1-loaded Fol-NSC micelles developed in the present study had suitable physicochemical properties. These nanocarriers may be a potential delivery system for targeted delivery of the 3A.1 to colorectal cancer cells.

Abstract: The objective of this research was to synthesized and evaluated a mucoadhesive catechol-bearing succinyl chitosan (Cat-SCS) as an innovative mucoadhesive substance for a mucoadhesive drug delivery system. Succinyl chitosan (SCS) was synthesized via ring-opening reactions with succinic anhydride. The Cat-SCS was then synthesized by reacting SCS with dopamine with the existence of N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDAC) and N-hydroxysulfosuccinimide (NHS). The successful functionalization of catechol onto chitosan backbone was verified using nuclear magnetic resonance spectroscopy (NMR) and Fourier transform infrared spectroscopy (FT-IR). Mucoadhesion studies were performed using rheology measurement and ex-vivo mucoadhesion test. The findings exposed that the synthesized Cat-SCS exhibited excellent mucoadhesive properties which was better than the intact CS. Further indirect studies verified the occurrence of polymer-mucin glycoproteins interactions. The catechol content of catechol moiety on the Cat-SCS was determined to be 0.377 using the ¹H NMR. The cytotoxicity test indicated the biocompatibility of the obtained polymer on human gingival fibroblast cells (HGF cells). Therefore, these results could advocate the capacity to use of Cat-SCS as an innovative mucoadhesive platform for mucoadhesive drug delivery.

Abstract: Electrostatic interactions of polymeric charges become one of the important factors to form the polyelectrolyte complexes (PECs). In this work, PECs has successfully created through the interaction between positive charges of chitosan (CS) and negative charges of pectin (PE) based on the effect of pH and pKa of the polymers. The formation of PECs provides small particle size, positive surface charge, and high %entrapment efficiency (%EE) after loaded metronidazole (MTZ). Dropwise addition of PE solution into CS solution was carried out to form PECs. A certain concentration of chitosan and pectin fixed at ratio 3:1 while the pH of both polymers varied as pH 1, 3, 5, and 9. The alterations after forming PECs observed particle size, zeta potential, and turbidity of the solution along with FTIR, DSC, and TAG. Precipitation of PECs solution was found in the fixed pH 5 of PE solution dropwise into pH 7 and 9 CS solution, which referred to the unstable of the PECs system. The pH 1 and 9 of PE and CS obtained the large size which about 600-1200 nm, while zeta potential found a low positive charge of 5.54-11.90 mV. Thus, only the fixed pH 5 of CS solution and pH 3, 5, or 7 of PE solution to form PECs were used to load MTZ. After loaded MTZ, the particle size of the PECs was about 400-500 nm and the zeta potential was about 20-50 mV. Electrostatic interactions resulted from FTIR detected the changes in amino groups of CS and carboxyl groups of PE. Thermal analysis on DSC for determinations of melting points or transition temperatures and TGA to monitor weight loss by heat were confirmed the PECs and MTZ-PECs formation. The pH 5 of PE interacts with pH 5 of CS offered the smallest particle size as 438 nm, zeta potential about 23.5 mV, and the highest percentage of EE as about 50% of the drug-loaded. The pH 5 of PE and CS were the pH-responsive to the pKa, thus, the acidity of the polymers may provide a suitable condition to form the appropriate polyelectrolyte complexes. Keywords: Polyelectrolyte complex, polycation, polyanion, charge density

Abstract: The purpose of this study was to design an enteric release tablet by a simple method of tableting and avoiding the coating process. Polymers which had a protection ability against acid were required for tablet formulation. Bleached shellac was selected as an excipient due to colorless property, a protection ability against acid in upper gastrointestinal tract and release ability in lower gastrointestinal tract. Bleached shellacs in salt and acid forms were dissolved in 12 ml of 95% ethanol and used as a binding agent to get a concentration of 5, 7.5, 10, 12.5, 15, 17.5 and 20 %w/w of total formulation. 60% lactose, 30% Avicel pH 102 and 10% paracetamol (model drug) were mixed and tablets were prepared by wet granulation method with the weight of 550 mg and hardness of 8-10 kg. The tablets were evaluated for their disintegration and drug release at pH 1.2 and 6.8 and kept at 40 °C, 75%RH for 6 months. The findings showed that the disintegration and amount of release were dependent on type and concentration of bleached shellac. Only the bleached shellac in salt form could protect the release of drug at pH 1.2 for 2 h and could release completely at pH 6.8 but not in acid form. After 6 months of storage, 15% bleached shellac in salt form could still protect against acid and complete release at pH 6.8 for 4 h. Although the bleached shellac showed protection ability against acid, it could not comply with the required criteria of enteric release tablet. Further study is hence required. However, the stability test of tablets prepared with bleached shellacs in salt form could show protection against acid and complete release at pH 6.8 after 6 months of storage. Bleached shellacs in salt form as a binding agent showed a good approach for the fabrication of enteric release tablets without coating process by using a proper concentration of bleached shellac. Therefore, the attempt to design an enteric tablet by a simple method and avoiding the coating process is achieved.

Abstract: The objective of this study was to optimize fabrication variables that affected desirable properties of dressings. Boesenbergia rotunda extract incorporated PVA hydrogels for wound dressings were fabricated by freeze-thaw method. The fabrication variables including PVA concentration (15, 17.5 and 20 % w/w), freeze-thaw cycle (2, 3 and 4 cycles) and extract loading (30, 40 and 50 % w/w) were studied and optimized. Effects of variables on the hydrogel wound dressing properties were determined by using Box-Behnken design and response surface method. Hydrogel properties such as tensile strength, elongation at break, Young’s Modulus, water content, swelling and erosion were measured and used as the designed responses. From statistical data analysis (p <0.05), the polynomial quadratic equation which indicated the significant effects of fabrication variables on the hydrogel properties was generated. In conclusion, desirable B. rotunda extract loaded PVA hydrogel dressing was favorably designed. The optimized PVA concentration, freeze-thaw cycle and extract loading were 17.07 % w/w, 3.86 cycles and 50 % w/w, respectively.

Abstract: This study aimed to evaluate the optimal conditions for crosslinked of PAMA/PVA microneedle (MN) arrays. Poly (acrylic acid-co-maleic acid) (PAMA)/poly (vinyl alcohol) (PVA) MN arrays were fabricated for the first time using the micromolding technique. The PAMA/PVA MN arrays at the polymer ratio of 1:4 were sharp, homogenous and perfectly formed with an elegant appearance. The successfully crosslinking MN arrays were determined using FTIR and water insolubilization. The results showed that increasing the crosslinking temperature and time, the degree of crosslinking also improved, which results in a decline in water uptake. The optimal crosslinking condition for PAMA/PVA MN arrays was 130°C for 1 h. Moreover, the highest swelling was observed from crosslinked PAMA/PVA MN arrays at 90°C for 0.5 h. These studies suggest that the combination of PAMA and PVA for fabrication of MN arrays could have a great potential to develop both hydrogel and dissolving MN devices for transdermal drug delivery.

Abstract: Polymethacrylates polymeric film formation in patches containing α-mangostin and resveratrol were developed using solvent casting method. Eudragit^® E100 (E) and Eudragit^® L100 (L) were dissolved in ethanol and the plasticizer (propylene glycol (PG) and polyethylene glycol (PEG) 400) was individual added and followed with the drying process. The dried films were evaluated for the morphology and flexibility. After the stable film was achieved, the α-mangostin and resveratrol were incorporated into the film. The variation of weight and thickness, swelling property, pH surface, mechanical properties and drug content of patches was evaluated. Fourier transform infrared spectrophotometry (FT-IR) was also conducted to confirm that drugs were qualitatively loaded into the patches. The results indicated that patch of L and PG was found to be stable. PG enhanced the flexibility of patch. The patches were less variation in weight and thickness. This patch did not effect to the physiological pH in the human body. In addition, patch had a tensile strength high enough to withstand tearing during handing. The qualitative and quantitative analysis indicated the α-mangostin and resveratrol was well incorporated in this patch. These results suggest that polymethacrylate polymer could be a promising polymeric film formation in patches for drug delivery.