Non-Gelatin-Based Capsules
Larry L. Augsburger, Stephen W. Hoag in Pharmaceutical Dosage Forms, 2017
Pullulan is polysaccharide derived by fermentation of starch. It is recognized as safe by the US Food and Drug Administration for use in food and pharmaceutical products (GRAS status). Pullulan has been identified as a suitable polymer for the commercial manufacturing of two-piece capsules using the traditional capsule manufacturing process of the addition of a gelling system.
Synthesis and characterization of polyethyleneimine-terminated poly(β-amino esters) conjugated with pullulan for gene delivery
Published in Pharmaceutical Development and Technology, 2022
Atena Farahpour, Navid Ramezanian, Leila Gholami, Saeedeh Askarian, Arsham Banisadr, Reza Kazemi Oskuee
Pullulan is a linear glucosic polysaccharide with the chemical structure of {→6)-α-d-glucopyranosyl-(1→4)-α-d-glucopyranosyl-(1→4)-α-d-glucopyranosyl-(1→}n. Due to its properties such as non-toxicity, non-carcinogenic, non-mutagenic, non-immunogenic, and high flexibility in aqueous solutions, as well as biocompatibility and biodegradability, it has been investigated in different biomedical applications comprising of gene delivery, targeted drug delivery, and tissue engineering (Kaneo et al. 2001; Na and Bae 2002; Singh et al. 2008; Cheng et al. 2011; Prajapati et al. 2013). Moreover, gene delivery is the main field in which pullulan application is being explored. Another point which is mentioned in various studies in regard to pullulan benefits is that liver which consists of many asialglycoprotein receptors (ASGPRs) that could be used as a target for pullulan in liver targeting (Yamaoka et al. 1993; Na and Bae 2002; Weigel and Yik 2002; Mehvar 2003). Polyethyleneimine (PEI) has held great promise for gene delivery. In most cases, only the high molecular weight PEIs enable to form bind with nucleic acids and lead to a high gene transfection efficiency. However, high molecular weight PEIs because of their intense cytotoxicity are not a good option for gene delivery application. In this study, pBAE was exploited as the basic polymer for gene carrier development, and low molecular weight PEI (MW 1800 Da) acts as a cationic polymer modifier with low toxicity to improve the water solubility and charge of the basic polymer.
Assessing the viability of carbamoylethyl pullulan-g-stearic acid based smart polymeric micelles for tumor targeting of raloxifene
Published in Drug Development and Industrial Pharmacy, 2021
Sheshank Sethi, Sachin Bhatia, Sunil Kamboj, Ram Sarup Singh, Vikas Rana
Among the smart polymers, pullulan is a microbial polysaccharide that has been widely used in tissue engineering and biological medicine owing to its non-toxicity, good biocompatibility, and biodegradability. In addition, the derivatization of polysaccharides enhances their anti-oxidant activity by attaining higher scavenging effect of the derivative at lower IC50 value [10,11]. However, no attempt has been made to explore the imide derivative of pullulan as a drug carrier in diseased or healthy animal models.
Pullulan based derivatives: synthesis, enhanced physicochemical properties, and applications
Published in Drug Delivery, 2022
Surendra Agrawal, Divya Budhwani, Pravina Gurjar, Darshan Telange, Vijay Lambole
Pullulan is a highly biocompatible and biodegradable polymer that can be used as a carrier to deliver macromolecules. It is a water-soluble polymer with hydrophilic properties, making it difficult to encapsulate hydrophobic and charged protein (Bruneel & Schacht, 1994). To overcome this issue, hydrophobic or charged segments were introduced in pullulan. Succinylation results in the incorporation of the carboxylic group into pullulan [Pullulan acetate (PLAc), pullulan propionate (PLPr), and pullulan butylate (PLBu)] by reaction with negatively charged succinic anhydride (acetic anhydride, propionic anhydride, and butyric anhydride) that makes it appropriate for drug delivery of positively charged protein (Niu et al., 2019). As shown in Figure 3, succinylation occurs in the presence of catalyst DMSO (4-dimethylaminopyridine) at 40 °C for 24 h. The preferred site of succinic anhydride in pullulan is C-6. Succinylated pullulan requires activation of COOH group by N,N′-carbonyldiimidazol. The resulting derivative can be coupled with the amine (Bruneel & Schacht, 1994). A microsphere was prepared using SPA (succinylated pullulan acetate) to carry protein. In the microsphere, PLGA [poly(dl-lactic acid-co-glycolic acid)] was replaced with SPA and loaded with lysozyme (Lys) as a model protein drug using the double emulsion method. This microsphere resulted in long-term protein stability and three times higher protein loading efficiency. Therefore, protein can be delivered with long-term stability using SPA (Woo et al., 2011). A film to extend the shelf life of fruit was also prepared. They packed strawberries with pullulan acetate film, which showed reduced weight loss percentage and enhanced shelf life of strawberries with its antioxidant property and by exhibiting high water contact angle. This indicated the pullulan as a promising material for the edible coating to extend the shelf life (Niu et al., 2019).