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Koushik Barman, Shikha P Barman, Kevin Ward; Sustained Release Micro-Encapsulates to Administer Peptides, Proteins and Nucleic Acids for Retinal Diseases. Invest. Ophthalmol. Vis. Sci. 2014;55(13):466.
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Retinal diseases warrants development of receptor-specific molecules targeting cellular mechanisms to arrest further disease progression, thus preventing ultimate blindness. Proteins, peptides and nucleic acids demonstrate immense potential as treatment modalities. These therapies are administered via repeated injections, leading to issues such as endophthalmitis and retinal detachment. Delivery systems releasing predictable levels of intact drug into the vitreous for multiple months can revolutionize treatment of retinal diseases. One advantage of encapsulating drugs is the protection of biologics from rapid in-vivo degradation. Development objectives for these delivery systems include achievement of high encapsulation efficiencies of intact drug, retention of biological potency of the encapsulated drug throughout delivery and precise release of the drug over time. One major issue encountered during the encapsulation process is the loss of the water-soluble drug, resulting in very low encapsulation efficiencies and typically, high "burst" release. We developed encapsulated a highly soluble 39-amino acid peptide as a model compound in poly(lactide-co-glycolide) (PLG) with encapsulation efficiencies greater than 90%, percent "burst" less than 1% and sustained release profiles to 60 days in phosphate buffered saline, pH 7.4.
A water-soluble 39-amino acid peptide of M.W. 4310 Daltons was encapsulated into PLG microparticles. Encapsulation efficiency was measured by dissolution of the microparticles in ethyl acetate, then aqueous extraction of the drug from the PLG polymer prior to analysis. Particle size distribution was measured using a Horiba LA-950. Scanning electron microscopy was used to determine internal microstructure of the microparticles. In-vitro release studies were performed in PBS at 37°C, pH 7.4.
Intact peptide was encapsulated in PLG microparticles with efficiencies of 85-90%. The process produced non-porous microstructures (measured by SEM), leading to bursts < 1% and drug release for ~60-70 days. Microparticle size was ~56 microns, injectable via a 27G needle. The process to fabricate these delivery systems were scaled up to 10L.
Efficient encapsulation and sustained release of peptides from microencapsulates was achieved, warranting further development.
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