Biocompatible microgels

Biocompatible microgels for the delivery of protein and DNA biomolecules were developed using acrylamide monomer, a bisacrylamide acetal crosslinker and potassium persulphate initiator. Encapsulation was shown to provide protection from enzymatic degradation of the protein or DNA. These particles demonstrated pH sensitivity such that in an acidic environment, as in the lysosome, the polymeric carrier degraded and released the encapsulated biomolecule. 9 refs. 

As carriers for proteins and enzymes biocompatible reactive microgels must be synthesized which are soluble in the serum at 37 °C. Moreover they should be hydrophilic enough that no ionic monomers are needed but they should not be soluble in water. An inert comonomer should serve as a spacer as well as a reactive solvent that may dissolve solid comonomers. The coupling reaction should be possible under mild reaction conditions. 

As mentioned above, the preparation of nanogels by addition reactions of functional macromolecular precursors is mainly used for biomedical applications. Thus, the choice of synthetic precursors for microgel formation is restricted to biocompatible materials. Moreover, as most applications are in drug delivery, the molecular weight of the gel precursors should be below the threshold for renal clearance, a value that depends on the molecular architecture and chemical nature of the polymer but that is usually smaller than 30kDa, which is set as the limit for linear PEG [97], Polymers that are mostly used and thus presented in more detail here are PEG, poly(glycidol) (PG), and polyethylene imine) (PEI). 

Zhang, H. Mardyani, S. Chan, W.C.W. Kumacheva, E. Design of biocompatible chitosan microgels for targeted pH-mediated intracellular release of cancer therapeutics. Biomacromolecules 2006, 7 (5), 1568-1572. 

Chastek, T., A. Wadajkar, et al. (2010). Polyglycol-templated synthesis of poly(N-isopropyl acrylamide) microgels with improved biocompatibility. Colloid Polymer Science 288(1) 105-114. 

Sisson, A. L., D. Steinhilber, et al. (2009). Biocompatible functionalized polyglycerol microgels with cell penetrating properties. Angew Chem IntEd Engl 48(41) 7540— 7545. 

Q. Yang, K. Wang, J. Nie, B. Du, cuid G. TcUig, Poly(N-vinylpyrrolidtnone) microgels preparation, biocompatibility cuid potenticd application as drug Ccurier, Biomacromolecules, 15 (6), 2285-2293, 2014. 

Dhar N, Akhlaghi SP, Tam KC. Biodegradable and biocompatible polyampholyte microgels derived from chitosan, carboxymethyl cellulose and modified methyl cellulose. Carbohydr Polym 2012 87 101-109. 

Thermally sensitive polymers under colloidal nano and microgels are also started to be used in drug delivery and the most examined polymers are poly(A-alkylacrylamide) derivatives. Unfortunately, such polymers are biocompatible but not biodegradable, and they are mainly used... 

In order to verily that the microgel samples are in general biocompatible we used a cell proliferation assay. AU microgel samples were proven cytocompatible throughout the 6-day cell culture experiment, with no significant effect on cell proliferation. These results demonstrate that ES12 microgels may be used for further in vitro or in vivo experiments. 

Hollow silica gels were prepared using PNlPAAm by Liu et al. Rhodamine B was taken as the model drug, it was observed that the LCST of the PNlPAAm was increased to 40.6°C, which indicates a good performance of temperature-dependent phase transition. To further confirm the temperature responsiveness of the system, the release study was carried out at 25°C and 40°C. it was observed that 82.5% of the RHB was released for 12 h at 25°C while 86.5% was released at 40°C in 12 h. Thus, this indicates the prepared microgels achieve thermoresponsive controlled release behavior and were also found to be biocompatible [36]. Some of the applications of thermoresponsive polymers in drug delivery are summarised in Table 20.1. 

The release study at 25°C and at 40°C indicates the RHB release of 82.5% for 12 h at 25°C while 86.5% was released at 40°C in 12 h. Thus, this indicates the prepared microgels achieve thermoresponsive controlled release behavior and were also found to be biocompatible. 

Biocompatibility refers to the inertness of microgels and the absence of undesirable physiological reactions, including reaction with plasma proteins, immune response, toxicity, and vascular damage. The high water content of microgels makes them soft and flexible, and, thus, these networks... 

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