Owing to their tunable properties, controllable degradation, and ability to protect labile drugs, hydrogels are increasingly investigated as local drug delivery systems. However, a lack of standardized methodologies used to characterize and evaluate drug release poses significant difficulties when comparing findings from different investigations, preventing an accurate assessment of systems. Here, we review the commonly used analytical techniques for drug detection and quantification from hydrogel delivery systems. The experimental conditions of drug release in saline solutions and their impact are discussed, along with the main mathematical and statistical approaches to characterize drug release profiles. We also review methods to determine drug diffusion coefficients and in vitro and in vivo models used to assess drug release and efficacy with the goal to provide guidelines and harmonized practices when investigating novel hydrogel drug delivery systems.

https://www.mdpi.com/1999-4923/12/12/1188/pdf

Hydrogels as Drug Delivery Systems: A Review of Current Characterization and Evaluation Techniques.

Modulating angiogenesis with integrin-targeted nanomedicines.

5-Fluorouracil (5-FU) is an antimetabolite widely used in the treatment of a variety of solid tumors. However, its clinical applications are greatly hindered by a very short residence time in blood circulation and non-specific distribution in the body. In order to overcome these challenges, 1-alkylcarbonyloxymethyl 5-FU was designed and linked with a maleimide group to form an albumin-binding 5-FU prodrug, named EMC-5-FU. In vitro incubation with bovine serum albumin (BSA) and fresh rat blood proved that the prodrug bound rapidly to cysteine-34 to form the drug–albumin conjugate nanomedicine. The conjugate BSA–EMC-5-FU was stable under acidic and neutral conditions but an unstable compound to release 5-FU in alkaline solution, and such a property was used for the determination of total 5-FU concentration in plasma. The t1/2 and AUC values of total 5-FU after an intravenous injection of EMC-5-FU to SD rats were significantly increased, about 43-fold and 93-fold higher than those of 5-FU following 5-FU intravenous administration, respectively. In vivo fluorescence images of EMC-Cy5 indirectly demonstrated the selective tumor accumulation of EMC-5-FU. In H22 tumor-bearing mice models, treatment with EMC-5-FU was more efficacious in tumor inhibition compared to 5-FU intravenous administration. In conclusion, a rapid albumin-binding prodrug strategy addresses concerns related to the poor circulation half-life and non-specific distribution of anticancer drugs, and paves the way for the development of in vivo-forming nanomedicines in clinical cancer therapy.

A rapid albumin-binding 5-fluorouracil prodrug with a prolonged circulation time and enhanced antitumor activity

Biodegradable brush-type copolymer modified with targeting peptide as a nanoscopic platform for targeting drug delivery to treat castration-resistant prostate cancer.

Increasing the anticancer performance of bufalin (BUF) by introducing an endosome-escaping polymer and tumor-targeting peptide in the design of a polymeric prodrug.

We report on the fabrication of a multifunctional polymeric prodrug covalently linked with an anticancer drug (bufalin, BUF) and tumor-targeting peptide (RGD) and investigate its anticancer performance against colon cancer in mice. The polymerizable monomer, 3-((2-(methacryloyloxy)ethyl) thio)propanoic acid (BSMA), was synthesized first. Atom radical transfer polymerization (ATRP) of BSMA and oligo(ethylene glycol) monomethyl ether methacrylate (OEGMA) afforded random copolymers, P(OEGMA-co-BSMA). The polymeric prodrug of BUF, P(OEGMA-co-BUF), was obtained by an esterification reaction between the carboxyl groups of P(OEGMA-co-BSMA) and the hydroxyl group of BUF. Finally, a tumor-targeting polymeric prodrug, P(OEGMA-co-BUF-co-RGD), was obtained via an aminolysis reaction of P(OEGMA-co-BUF) in the presence of RGD and the final drug content was determined to be ∼32.9 wt%. In aqueous media, P(OEGMA-co-BUF-co-RGD) self-assembles into micelles and the hydrodynamic diameter (Dh) of the micelles was determined to be ∼33.0 (±2.5) nm by dynamic laser light scattering (LLS). It was demonstrated that the tumor-targeting polymeric prodrug showed improved anticancer performance both in vitro and in vivo in comparison with that of free BUF.

Esterase-responsive polymeric prodrug-based tumor targeting nanoparticles for improved anti-tumor performance against colon cancer

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Esterase-responsive polymeric prodrug-based tumor targeting nanoparticles for improved anti-tumor performance against colon cancer