Hyaluronan delivery

Upadhyay KK, Bhatt AN, Mishra AK, Dwarakanath BS, Jain S, Schatz C, Le Meins JE, Earooque A, Chandraiah G, Jain AK, Misra A, Lecommandoux S (2010) The intracellular drug delivery and anti tumor activity of doxorubicin loaded poly(y-benzyl L-glutamate)-b-hyaluronan polymersomes. Biomaterials 31(10) 2882... 

Luo, Y., et al. 2002. Targeted delivery of doxorubicin by HPMA copolymer-hyaluronan bioconjugates. Pharm Res 19 396. 

Lim, S.T., et al. 2002. In vivo evaluation of novel hyaluronan/chitosan microparticulate delivery systems for the nasal delivery of gentamicin in rabbits. Int J Pharm 231 73. 

Different drug delivery systems have been proposed for vaginal delivery of peptides and proteins. The first one was a mucoadhesive gel based on polyacrylic acid intended for vaginal administration of insulin [96]. More recently, microparticulate systems such as starch and hyaluronan ester (HYAFF) microspheres have been proposed for vaginal delivery of insulin... 

Abstract Carbohydrates have been investigated and developed as delivery vehicles for shuttling nucleic acids into cells. In this review, we present the state of the art in carbohydrate-based polymeric vehicles for nucleic acid delivery, with the focus on the recent successes in preclinical models, both in vitro and in vivo. Polymeric scaffolds based on the natural polysaccharides chitosan, hyaluronan, pullulan, dextran, and schizophyllan each have unique properties and potential for modification, and these results are discussed with the focus on facile synthetic routes and favorable performance in biological systems. Many of these carbohydrates have been used to develop alternative types of biomaterials for nucleic acid delivery to typical polyplexes, and these novel materials are discussed. Also presented are polymeric vehicles that incorporate copolymerized carbohydrates into polymer backbones based on polyethylenimine and polylysine and their effect on transfection and biocompatibility. Unique scaffolds, such as clusters and polymers based on cyclodextrin (CD), are also discussed, with the focus on recent successes in vivo and in the clinic. These results are presented with the emphasis on the role of carbohydrate and charge on transfection. Use of carbohydrates as molecular recognition ligands for cell-type specific dehvery is also briefly... 

One such application could be delivery of Has2-pDNA, a plasmid that codes for hyaluronan synthase 2 [66]. This enzyme facilitates the synthesis of larger HA molecules and can prevent post-surgical peritoneal adhesions. In one study, DNA-HA films were prepared using previously-described chemistry however, lyophili-zation was replaced with air-drying under sterile conditions and an isopropanol/ H20 mixture was used instead of DMF/H20. The release kinetics of DNA were similar to that from the HA film described previously, but release did not occur until after 7 days. The reason for this delay was not completely clear the authors suggest that a possible way to overcome the delay is to use a crosslinked DNA-HA film sandwiched between two non-crosslinked DNA-HA films. Non-crosslinked film... 

Recently, other approaches and modifications of HA for gene delivery applications have been investigated. Among the most interesting ones are mixed chitosan-hyaluronan based gene delivery systems [68-70] and PEG-HA photocrosslinked hydrogels [71]. HA has also been used to improve the biocompatibility of branched PEI via covalent conjugation [72],... 

Yun YH, Goetz DJ, Yellen P et al (2004) Hyaluronan microspheres for sustained gene delivery and site-specific targeting. Biomaterials 25(1) 147-157... 

Kim AP, Yellen P, Yun YH et al (2005) Delivery of a vector encoding mouse hyaluronan synthase 2 via a crosslinked hyaluronan film. Biomaterials 26 1585-1593... 

Yun YH, Chen W (2005) Microspheres formulated from native hyaluronan for applications in gene therapy. In Mansoor MA (ed) Polymeric gene delivery principles and applications, CRC Press LLC, USA, pp 475 186... 

Research on nasal powder drug delivery has employed polymers such as starch, dextrans, polyacrylic acid derivatives (e.g., carbopol, polycarbophil), cellulose derivatives (microcrystalline cellulose, semicrystalline cellulose, hydroxypropylmethyl cellulose, hydroxypropyl cellulose, carboxymethyl cellulose), chitosan, sodium alginate, hyaluronans, and polyanhydrides such as poly(methyl vinyl ether-co-maleic anhydride) (PVM/MA). Many of these polymers have already been used as excipients in pharmaceutical formulations and are often referred to as first-generation bioadhesives [38-45], In nasal dry powder a single bioadhesive polymer or a... 

Hyaluronan is used therapeutically to treat osteoarthritis in the knee, and is an effective treatment for arthritic pain. Crosslinked hyaluronan gels are used as drug delivery systems. 

Hyaluronan is the most common negatively charged glycosaminoglycan in the human vitreous humor, and is known to interact with polymeric and liposomal DNA complexes, where hyaluronan solutions have been shown to decrease the cellular uptake of complexes.This is useful for enhancing the availability and retention time of drugs administered to the eye. It is immunoneutral, which makes it useful for the attachment of biomaterials for use in tissue engineering and drug delivery... 

Ghezzo E, Beredetti LM, Rochira M, et al. Hyaluronan derivative microspheres as NGF delivery devices preparation methods and in vitro release characterization. Int ] Pharm 1992 29 133-141. 

Microspheres prepared from hyaluronan esters have been evaluated for the vaginal administration of calcitonin in the treatment of postmenopausal osteoporosis. Microspheres prepared from hyaluronan esters have also been used experimentally as delivery devices for nerve growth factors, and as a nasal delivery system for insulin. ... 

The second major role for carbohydrate in skin tissue engineering is in cell delivery. In this respect, the most widely used carbohydrate is hyaluronan. 

D. Hyaluronan-Mediated Enhanced Transdermal Delivery of Chemotherapeutics... 

H. Hyaluronan as a Delivery Vehicle for Cartilage and Bone Repair Applications... 

Gianolio DA, Philbrook M, Avila LZ, MacGregor H, Duan SX, Bernasconi R, Slavsky M, Dethlefsen S, Jarrett PK, Miller RJ. Synthesis and evaluation of hydrolyzable hyaluronan-tethered bupivacaine delivery systems. Bioconjug Chem 2005 16 1512-1518. 

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