scholarly journals Effect of Process Parameters on the Initial Burst Release of Protein-Loaded Alginate Nanospheres

2019 ◽  
Vol 10 (3) ◽  
pp. 42 ◽  
Author(s):  
Farhana Yasmin ◽  
Xiongbiao Chen ◽  
Brian Eames

The controlled release or delivery of proteins encapsulated in micro/nanospheres is an emerging strategy in regenerative medicine. For this, micro/nanospheres made from alginate have drawn considerable attention for the use as a protein delivery device because of their mild fabrication process, inert nature, non-toxicity and biocompatibility. Though promising, one key issue associated with using alginate micro/nanospheres is the burst release of encapsulated protein at the beginning of the release, which may be responsible for exerting toxic side effects and poor efficiency of the delivery device. To address this issue, this study aimed to investigate the effect of process parameters of fabricating protein-loaded alginate nanospheres on the initial burst release. The alginate nanospheres were prepared via a combination of water-in-oil emulsification and the external gelation method and loaded with bovine serum albumin (BSA) as a model protein. The examined process parameters included alginate concentration, ionic cross-linking time and drying time. Once fabricated, the nanospheres were then subjected to the examination of BSA release, as well as the characterization of their morphology, size, and encapsulation efficiency. Our results revealed that by properly adjusting the process parameters, the initial burst release can be reduced by 13%. Taken together, our study demonstrates that regulating process parameters of fabricating alginate nanospheres is a possible means to reduce the initial burst release.

Pharmaceutics ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 305 ◽  
Author(s):  
Bishweshwar Pant ◽  
Mira Park ◽  
Soo-Jin Park

Electrospinning has emerged as one of the potential techniques for producing nanofibers. The use of electrospun nanofibers in drug delivery has increased rapidly over recent years due to their valuable properties, which include a large surface area, high porosity, small pore size, superior mechanical properties, and ease of surface modification. A drug loaded nanofiber membrane can be prepared via electrospinning using a model drug and polymer solution; however, the release of the drug from the nanofiber membrane in a safe and controlled way is challenging as a result of the initial burst release. Employing a core-sheath design provides a promising solution for controlling the initial burst release. Numerous studies have reported on the preparation of core-sheath nanofibers by coaxial electrospinning for drug delivery applications. This paper summarizes the physical phenomena, the effects of various parameters in coaxial electrospinning, and the usefulness of core-sheath nanofibers in drug delivery. Furthermore, this report also highlights the future challenges involved in utilizing core-sheath nanofibers for drug delivery applications.


Pharmaceutics ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 683
Author(s):  
Jebun Nessa Diana ◽  
Ying Tao ◽  
Qiran Du ◽  
Meng Wang ◽  
Chinta Uday Kumar ◽  
...  

The challenges of formulating recombinant human growth hormone (rhGH) into sustained-release polymeric microspheres include two mutual causal factors, protein denaturing by the formulation process and severe initial burst release related with relative high dose. The stabilizers to protect the proteins must not evoke osmotic pressure inside the microspheres, and the contact of the protein with the interface between water and organic solution of the polymer must be minimized. To meet these criteria, rhGH was pre-formulated into polysaccharide particles via an aqueous–aqueous emulsion in the present study, followed by encapsulating the particles into microspheres through a self-regulated process to minimize the contact of the protein with the water–oil interface. Polysaccharides as the protein stabilizer did not evoke osmotic pressure as small sugar stabilizers, the cause of severe initial burst release. Reduced initial burst enabled reduced protein loading to 9% (from 22% of the once commercialized Nutropin depot), which in turn reduced the dosage form index from 80 to 8.7 and eased the initial burst. A series of physical chemical characterizations as well as biologic and pharmacokinetic assays confirmed that the present method is practically feasible for preparing microspheres of proteins.


2017 ◽  
Vol 65 (7) ◽  
pp. 653-659 ◽  
Author(s):  
Mai Hazekawa ◽  
Honami Kojima ◽  
Tamami Haraguchi ◽  
Miyako Yoshida ◽  
Takahiro Uchida

Drug Research ◽  
2017 ◽  
Vol 67 (08) ◽  
pp. 458-465 ◽  
Author(s):  
Alireza Nomani ◽  
Hamed Nosrati ◽  
Hamidreza Manjili ◽  
Leila Khesalpour ◽  
Hossein Danafar

AbstractBiodegradable copolymeric polymersomes have been used for controlled drug delivery of proteins. These polymersomes important areas to overcome formulation associated problems of the proteins. The aim of this study was to develop polymersomes using biodegradable copolymers for delivery of bovine serum albumin (BSA) as a model protein. Encapsulated BSA by mPEG-PCL polymersomes led to formation of BSA-loaded mPEG-PCL polymersomes. The polymersomes synthesized with the protein-polymer ratio of 1:4 at 15 000 rpm gave maximum loading, minimum polydispersion with maximally sustained protein release pattern, among the prepared polymersomes. Investigation on FTIR and DSC results revealed that such a high encapsulation efficiency is due to strong interaction between BSA and the copolymer.The particles size and their morphology of polymersomes were determined by DLS and AFM.The encapsulation efficiency of BSA was 91.02%. The results of AFM showed that the polymersomes had spherical shapes with size of 49 nm.The sizes of BSA-loaded polymersomes ranged from 66.06 nm to 84.97 nm. The results showed that polymersomes exhibited a triphasic release, for BSA. Overall, the results indicated that mPEG–PCL polymersomes can be considered as a promising carrier for proteins.


2012 ◽  
Vol 1418 ◽  
Author(s):  
Chong Wang ◽  
Min Wang ◽  
Xiao-Yan Yuan

ABSTRACTElectrospinning is a versatile technique for fabricating three-dimensional (3D) nanofibrous scaffolds and the scaffolds have been found to elicit desirable cellular behavior for tissue regeneration because the nanofibrous structures mimic the nanofibrous extracellular matrix (ECM) of biological tissues. From the material point of view, the ECM of bone is a nanofibrous nanocomposite consisting of an organic matrix (mainly collagen) and inorganic bone apatite nanoparticles. Therefore, for bone tissue engineering scaffolds, it is natural to construct nanofibrous nanocomposites having a biodegradable polymer matrix and nanosized bioactive bioceramics. Our previous studies demonstrated: (1) electrospun nanocomposite fiber loaded with calcium phosphate (Ca-P) were osteoconductive and could promote osteoblastic cell proliferation and differentiation better than pure polymer fibers; (2) The controlled release of recombinant human bone morphogenetic protein (rhBMP-2) from scaffolds provided the scaffolds with desired osteoinductivity. In the current investigation, novel bicomponent scaffolds for bone tissue engineering were produced using our established dual-source dual-power electrospinning technique to achieve both osteoconductivity and osteoinductivity. In the bicomponent scaffolds, one fibrous component was electrospun Ca-P/PLGA nanocomposite fibers and the other component was emulsion electrospun PDLLA nanofibers incorporated with rhBMP-2. Through electrospinning optimization, both fibers were evenly distributed in bicomponent scaffolds. The mass ratio of rhBMP-2/PDLLA fibers to Ca-P/PLGA fibers in bicomponent scaffolds could be controlled using multiple syringes. The structure and morphology of mono- and bicomponent scaffolds were examined. The in vitro release of rhBMP-2 from mono- and bicomponent scaffolds showed different release amount but similar release profile, exhibiting an initial burst release. Blending PDLLA with polyethylene glycol (PEG) could reduce the initial burst release of rhBMP-2.


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