Systematic Modification and Evaluation of Enzyme-Loaded Chitosan Nanoparticles

Polymeric-based nano drug delivery systems have been widely exploited to overcome protein instability during formulation. Presently, a diverse range of polymeric agents can be used, among which polysaccharides, such as chitosan (CS), hyaluronic acid (HA) and cyclodextrins (CDs), are included. Due to its unique biological and physicochemical properties, CS is one of the most used polysaccharides for development of protein delivery systems. However, CS has been described as potentially immunogenic. By envisaging a biosafe cytocompatible and haemocompatible profile, this paper reports the systematic development of a delivery system based on CS and derived with HA and CDs to nanoencapsulate the model human phenylalanine hydroxylase (hPAH) through ionotropic gelation with tripolyphosphate (TPP), while maintaining protein stability and enzyme activity. By merging the combined set of biopolymers, we were able to effectively entrap hPAH within CS nanoparticles with improvements in hPAH stability and the maintenance of functional activity, while simultaneously achieving strict control of the formulation process. Detailed characterization of the developed nanoparticulate systems showed that the lead formulations were internalized by hepatocytes (HepG2 cell line), did not reveal cell toxicity and presented a safe haemocompatible profile.

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Structural characterization of the 5' regions of the human phenylalanine hydroxylase gene

Biochemistry ◽

10.1021/bi00150a033 ◽

1992 ◽

Vol 31 (35) ◽

pp. 8363-8368 ◽

Cited By ~ 28

Author(s):

David S. Konecki ◽

Yibin Wang ◽

Friedrich K. Trefz ◽

Uta Lichter-Konecki ◽

Savio L. C. Woo

Keyword(s):

Structural Characterization ◽

Phenylalanine Hydroxylase ◽

Hydroxylase Gene ◽

Phenylalanine Hydroxylase Gene ◽

Human Phenylalanine Hydroxylase

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Predicting protein instability in sustained protein delivery systems using spectral-phase interference

Biomaterials ◽

10.1016/j.biomaterials.2011.11.037 ◽

2012 ◽

Vol 33 (6) ◽

pp. 1929-1938 ◽

Cited By ~ 9

Author(s):

Nina Seidel ◽

Johannes Sitterberg ◽

Wolfgang Vornholt ◽

Udo Bakowsky ◽

Michael Keusgen ◽

...

Keyword(s):

Protein Delivery ◽

Delivery Systems ◽

Spectral Phase ◽

Phase Interference ◽

Protein Instability

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Chitosan Based Nanoparticles in Drug Delivery

International Journal of Pharmaceutical Sciences and Nanotechnology ◽

10.37285/ijpsn.2009.2.2.4 ◽

2009 ◽

Vol 2 (2) ◽

pp. 517-522 ◽

Cited By ~ 2

Author(s):

J. K. Patel ◽

N. P. Jivani

Keyword(s):

Drug Delivery ◽

Drug Delivery Systems ◽

Chitosan Nanoparticles ◽

Synthetic Polymers ◽

Delivery Systems ◽

Natural Polymers ◽

Different Characteristics ◽

Hydrophilicity And Hydrophobicity ◽

Nanoparticulate Systems ◽

Natural And Synthetic

Nanoparticles have gained considerable attention in recent years as one of the most promising drug delivery systems owing to their unique potentials via combining the different characteristics of hydrophilicity and hydrophobicity with a nanoparticle (e.g., very small size). Several polymeric nanoparticulate systems have been prepared and characterized in recent years, based on both natural and synthetic polymers, each with its own advantages and drawbacks. Among the natural polymers, chitosan has been studied extensively for preparation of nanoparticles. Chitosan nanoparticles have been reported with different characteristics with respect to drug delivery. This review presents various types of chitosan based nanoparticles in drug delivery.

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Preparation and Characterization of Water-Soluble Chitosan Nanoparticles as Protein Delivery System

Journal of Nanomaterials ◽

10.1155/2010/898910 ◽

2010 ◽

Vol 2010 ◽

pp. 1-5 ◽

Cited By ~ 34

Author(s):

Hong-liang Zhang ◽

Si-hui Wu ◽

Yi Tao ◽

Lin-quan Zang ◽

Zheng-quan Su

Keyword(s):

Delivery System ◽

Protein Delivery ◽

Sodium Tripolyphosphate ◽

Chitosan Nanoparticles ◽

Water Soluble ◽

Preparation Conditions ◽

Model Drug ◽

Size And Morphology

The objective of this study was to investigate the potential of water soluble chitosan as a carrier in the preparation of protein-loaded nanoparticles. Nanoparticles were prepared by ionotropic gelation of water-soluble chitosan (WSC) with sodium tripolyphosphate (TPP). Bovine serum albumin (BSA) was applied as a model drug. The size and morphology of the nanoparticles were investigated as a function of the preparation conditions. The particles were spherical in shape and had a smooth surface. The size range of the nanoparticles was between 100 and 400 nm. Result of the in vitro studies showed that the WSC nanoparticles enhance and prolong the intestinal absorption of BSA. These results also indicated that WSC nanoparticles were a potential protein delivery system.

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Phenylketonuria in China: Identification and characterization of three novel nucleotide substitutions in the human phenylalanine hydroxylase gene

Human Mutation ◽

10.1002/humu.1380030323 ◽

1994 ◽

Vol 3 (3) ◽

pp. 312-314 ◽

Cited By ~ 2

Author(s):

Jia Li ◽

Randy C. Eisensmith ◽

Tao Wang ◽

Wilson H. Y. Lo ◽

Shu-Zhen Huang ◽

...

Keyword(s):

Phenylalanine Hydroxylase ◽

Nucleotide Substitutions ◽

Hydroxylase Gene ◽

Phenylalanine Hydroxylase Gene ◽

Human Phenylalanine Hydroxylase ◽

Identification And Characterization

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Factors Affecting Extracellular Vesicles Based Drug Delivery Systems

Molecules ◽

10.3390/molecules26061544 ◽

2021 ◽

Vol 26 (6) ◽

pp. 1544

Author(s):

Isha Gaurav ◽

Abhimanyu Thakur ◽

Ashok Iyaswamy ◽

Xuehan Wang ◽

Xiaoyu Chen ◽

...

Keyword(s):

Drug Delivery ◽

Extracellular Vesicles ◽

Targeted Delivery ◽

Drug Delivery Systems ◽

Delivery Systems ◽

Factors Affecting ◽

Open Questions ◽

Nano Drug Delivery ◽

Different Origins

Extracellular vesicles (EVs) play major roles in intracellular communication and participate in several biological functions in both normal and pathological conditions. Surface modification of EVs via various ligands, such as proteins, peptides, or aptamers, offers great potential as a means to achieve targeted delivery of therapeutic cargo, i.e., in drug delivery systems (DDS). This review summarizes recent studies pertaining to the development of EV-based DDS and its advantages compared to conventional nano drug delivery systems (NDDS). First, we compare liposomes and exosomes in terms of their distinct benefits in DDS. Second, we analyze what to consider for achieving better isolation, yield, and characterization of EVs for DDS. Third, we summarize different methods for the modification of surface of EVs, followed by discussion about different origins of EVs and their role in developing DDS. Next, several major methods for encapsulating therapeutic cargos in EVs have been summarized. Finally, we discuss key challenges and pose important open questions which warrant further investigation to develop more effective EV-based DDS.

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Identification and characterization of a novel liver-specific enhancer of the human phenylalanine hydroxylase gene

Human Genetics ◽

10.1007/s00439-002-0677-7 ◽

2002 ◽

Vol 110 (3) ◽

pp. 235-243 ◽

Cited By ~ 9

Author(s):

Kuan-Ju Chen ◽

Hung-Kun Chao ◽

Kwang-Jen Hsiao ◽

Tsung-Sheng Su

Keyword(s):

Phenylalanine Hydroxylase ◽

Hydroxylase Gene ◽

Phenylalanine Hydroxylase Gene ◽

Human Phenylalanine Hydroxylase ◽

Identification And Characterization

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Expression and Characterization of the Catalytic Domain of Human Phenylalanine Hydroxylase

Archives of Biochemistry and Biophysics ◽

10.1006/abbi.1997.0435 ◽

1997 ◽

Vol 348 (2) ◽

pp. 295-302 ◽

Cited By ~ 24

Author(s):

S.Colette Daubner ◽

Patrick J. Hillas ◽

Paul F. Fitzpatrick

Keyword(s):

Catalytic Domain ◽

Phenylalanine Hydroxylase ◽

Human Phenylalanine Hydroxylase

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Chitosan Nanoparticles-Insight into Properties, Functionalization and Applications in Drug Delivery and Theranostics

Molecules ◽

10.3390/molecules26020272 ◽

2021 ◽

Vol 26 (2) ◽

pp. 272

Author(s):

Jhanvi Jhaveri ◽

Zarna Raichura ◽

Tabassum Khan ◽

Munira Momin ◽

Abdelwahab Omri

Keyword(s):

Drug Delivery ◽

Drug Release ◽

Drug Delivery Systems ◽

Chitosan Nanoparticles ◽

Controlled Drug Release ◽

Drug Regimen ◽

Delivery Systems ◽

Important Place ◽

Nano Drug Delivery ◽

Insight Into

Nanotechnology-based development of drug delivery systems is an attractive area of research in formulation driven R&D laboratories that makes administration of new and complex drugs feasible. It plays a significant role in the design of novel dosage forms by attributing target specific drug delivery, controlled drug release, improved, patient friendly drug regimen and lower side effects. Polysaccharides, especially chitosan, occupy an important place and are widely used in nano drug delivery systems owing to their biocompatibility and biodegradability. This review focuses on chitosan nanoparticles and envisages to provide an insight into the chemistry, properties, drug release mechanisms, preparation techniques and the vast evolving landscape of diverse applications across disease categories leading to development of better therapeutics and superior clinical outcomes. It summarizes recent advancement in the development and utility of functionalized chitosan in anticancer therapeutics, cancer immunotherapy, theranostics and multistage delivery systems.

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