Surfactant free preparation of biodegradable dendritic polyglycerol nanogels by inverse nanoprecipitation for encapsulation and release of pharmaceutical biomacromolecules

Steinhilber, Dirk; Witting, Madeleine; Zhang, Xuejiao; Staegemann, Michael H.; Paulus, Florian; Frieß, Wolfgang; Küchler, Sarah; Haag, Rainer

doi:10.1016/j.jconrel.2012.12.008

Cited by 137 publications

(132 citation statements)

References 54 publications

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“…Recent examples include a dendritic polyglycerol nanogel system that was used to encapsulate asparaginase under surfactant-free conditions using hydrophilic components 51 . A pH-sensitive benzacetal crosslinking agent enabled the triggered release of payload under acidic conditions with almost 100% recovery of enzymatic activity compared to a control.…”

Section: Advanced Formulations and Chemistrymentioning

confidence: 99%

Overcoming the challenges in administering biopharmaceuticals: formulation and delivery strategies

Mitragotri

Burke

Langer

2014

Nat Rev Drug Discov

1,331

1,037

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The formulation and delivery of biopharmaceutical drugs, such as monoclonal antibodies and recombinant proteins, poses substantial challenges owing to their large size and susceptibility to degradation. In this Review we highlight recent advances in formulation and delivery strategies — such as the use of microsphere-based controlled-release technologies, protein modification methods that make use of polyethylene glycol and other polymers, and genetic manipulation of biopharmaceutical drugs — and discuss their advantages and limitations. We also highlight current and emerging delivery routes that provide an alternative to injection, including transdermal, oral and pulmonary delivery routes. In addition, the potential of targeted and intracellular protein delivery is discussed.

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Section: Advanced Formulations and Chemistrymentioning

confidence: 99%

Overcoming the challenges in administering biopharmaceuticals: formulation and delivery strategies

Mitragotri

Burke

Langer

2014

Nat Rev Drug Discov

1,331

1,037

View full text Add to dashboard Cite

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“…PG has received attention as an antifouling surface coating over the last 10 years. PG has been used to impart stealth properties to a number of nanoparticulate systems, including inorganic nanoparticles, 206,207 liposomes, 208-210 nanogels, 211 and micelles. PG has been affixed to surfaces both as SAMs [194][195][196][197][198][199] and as polymer grafts.…”

Section: Poly(glycerol)mentioning

confidence: 99%

Antibiofouling polymer interfaces: poly(ethylene glycol) and other promising candidates

2015

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Nonspecific protein adsorption and/or microbial adsorption on biomedical materials adversely affects the efficacy of a range of biomedical systems, from implants and biosensors to nanoparticles. To address this problem, antibiofouling polymers can be coated on biomedical devices or built into nanoparticles to confer protein and/or microbial repellent properties. The current review provides an overview of the range of synthetic polymers currently used to this end and explores their biomedical potential. The most widely-used antifouling polymer, poly(ethylene glycol) (PEG) is reviewed alongside several promising alternatives, including zwitterionic polymers, poly(hydroxyfunctional acrylates), poly(2-oxazoline)s, poly (vinylpyrrolidone), poly(glycerol), peptides and peptoids. For each material, notable applications for both nanomedicine and macroscopic surface coatings are highlighted.

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“…29,36,37 As shown in Scheme 1, the crosslinking occurred through the complexation of 1,2-diols in dPG and boronic acids in dPGA-FPBA-CA. 29,36,37 As shown in Scheme 1, the crosslinking occurred through the complexation of 1,2-diols in dPG and boronic acids in dPGA-FPBA-CA.…”

Section: Preparation Of Ngca and Ngca-cc By Inverse Nanoprecipitaionmentioning

confidence: 99%

Multi-stage, charge conversional, stimuli-responsive nanogels for therapeutic protein delivery

Zhang

Haag

2015

Biomater. Sci.

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A boronate ester crosslinked zwitterionic nanogel (NGCA) with ATP/pH-sensitivity has been developed with an inverse nanoprecipitation technique to achieve a two-stage charge conversion that responds to tumor extracellular conditions (pH 6.5-6.8) and an intracellular acidic environment (pH 5-6). Cationic cytochrome C (CC), a therapeutic protein, has been encapsulated into NGCA through inverse nanoprecipitation via electrostatic interactions to form protein-loaded nanogel (NGCA-CC). By adjusting the ratio of the amino and carboxyl groups in the nanogels, negatively charged nanogels that are safer under physiological conditions (pH 7.4) can convert their surface charge to positive at tumor extracellular pH, which enhance their cellular uptake efficiency. The citraconic amide formed from citraconic anhydride and amine can be cleaved in the intracellular acidic organelles to expose more amino groups and facilitate endosomal escape. The release of CC is accelerated in the presence of 5 mM ATP or under acidic conditions. Confocal laser scanning microscopy (CLSM) and flow cytometry have shown that NGCA-CC's cell uptake is higher at pH 6.5 than at pH 7.4. MTT and real-time cell analysis (RTCA) have illustrated that there is more toxicity at pH 6.5 than at pH 7.4. The apoptosis process induced by CC was determined by flow cytometry.

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Surfactant free preparation of biodegradable dendritic polyglycerol nanogels by inverse nanoprecipitation for encapsulation and release of pharmaceutical biomacromolecules

Cited by 137 publications

References 54 publications

Overcoming the challenges in administering biopharmaceuticals: formulation and delivery strategies

Overcoming the challenges in administering biopharmaceuticals: formulation and delivery strategies

Antibiofouling polymer interfaces: poly(ethylene glycol) and other promising candidates

Multi-stage, charge conversional, stimuli-responsive nanogels for therapeutic protein delivery

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