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A hollow cylinder intravitreal implant was developed to achieve sustained release of protein to the retina for the treatment of retinal diseases. Hollow cylinders were fabricated by molding and cross-linking hyaluronic acid, the major component of the vitreous humor. Hollow cylinders were filled with a concentrated protein solution, and the properties of the cylinder walls were tested. Cross-linked hyaluronic acid hydrogels with swelling degrees as low as 2.7 were achieved as a means to extend the release of protein. Hollow cylinders were capable of releasing an antigen-binding fragment for over 4 months at a maximum release rate of 4 μg per day. Protein release from hollow cylinders was modeled using COMSOL Multiphysics ® software, and diffusion coefficients between 1.0 × 10 -11 and 3.0 × 10 -11 cm 2 /s yielded therapeutically effective levels of protein. Cylinders with a 1 mm outer radius were capable of loading >1 mg of protein while releasing at least 2.5 μg a day for over 4.5 months. Although smaller cylinders facilitate intravitreal placement, decreasing the cylinder radius severely limited drug loading. Design of hollow cylinder intravitreal implants must balance high drug loading to reduce device size with control of the diffusion coefficient to sustain protein release., (Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Thermally associating polymers, including gelatin, cellulose ethers (e.g., Methocels and poloxamers (e.g., Pluronics) have a long history of use in pharmacy. Over the past 20 years, significant advances in genetic engineering and the understanding of protein secondary and tertiary structures have been made. This has led to the development of a variety of polypeptides that do not occur naturally but can be expressed in recombinant cells and have useful properties that lend themselves to novel applications where current materials cannot perform. The most intensively studied motifs are derived from the consensus repeats of elastin and silk, as well as coiled-coil helices. Many of these designed polypeptides or 'artificial proteins' are thermally associating materials. This property can be exploited to develop solid dosage forms, injectable drug delivery systems, micro- or nanoparticle drug carriers, triggered or targeted release systems, or as a means of simplifying the purification process and thus reducing costs of production of these materials. This review focuses on the development and characterization of this novel class of biomaterials and examines their potential for pharmaceutical applications., (2006 Wiley-Liss, Inc. and the American Pharmacists Association)

Polymer erosion of matrices of similarly substituted hydroxypropyl methylcellulose (HPMC) polymers was examined, and drug release in terms of diffusion and erosion contributions was characterized, focusing on matrices containing either polymer alone or a drug content of 25% level with no added excipients. A novel approach was utilized to separate diffusional and erosional contributions to drug release. Diffusional drug release was determined by fitting release data versus (time)0.45, and the drug release due to erosion was quantified by subtracting the percent predicted for diffusional drug release from the total drug release at each specific time point. Drug release resulting from polymer erosion was linear versus time and was found to be a function of the number average molecular weight of the polymer. In contrast, diffusional release rates were comparable for all HPMC grades studied and, thus, were independent of number average molecular weight of the polymers studied. Under stirring conditions of 10-100 rpm as well as static condition, the detachment of individual polymer chains at the matrix surface occurred at a faster rate relative to diffusion away from the matrix surface. The erosion study indicated that polymer diffusion of the HPMC polymer chains through the aqueous diffusion layer was the rate-limiting step for polymer erosion. In general, polymer erosion was found to be inversely related to the polymer number average molecular weight. A scaling law was used to relate polymer erosion rate with the respective polymer number average molecular weight. Similar relationships were obtained for matrices with and without drug at a stirring rate of 100 rpm.