“…The morphology of the films was studied using SEM. Like other LBL films, the PEG-sCT/TA films also present a rough surface 34 (Figure S2A). The thickness of an 8-bilayer film was measured to be ~20 nm.Figure 1( A ) Chemical structure of TA.…”
Peptides have great potential as therapeutic agents, however, their clinic applications are severely hampered by their instability and short circulation half-life. Zero-order release carriers could not only extend the circulation lifetime of peptides, but also maintain the plasma drug level constant, and thus maximize their therapeutic efficacy and minimize their toxic effect. Here using PEGylated salmon calcitonin (PEG-sCT)/tannic acid (TA) film as an example, we demonstrated that hydrogen-bonded layer-by-layer films of a PEGylated peptide and a polyphenol could be a platform for zero-order peptide release. The films were fabricated under mild conditions. The second component, TA, is a natural product and presents potential therapeutic activities itself. Unlike common carriers, the new carrier releases the peptide via gradual disintegration of the film because of its dynamic nature. The release of PEG-sCT follows a perfect zero-order kinetics without initial burst release. In addition the release rate could be tuned via external stimuli, such as pH and temperature. When implanted in rats, the films could remain the plasma level of PEG-sCT constant over an extended period. Accordingly, the serum calcium level was reduced and maintained constant over the same period, suggesting an improved therapeutic efficacy of the released drug.
“…The morphology of the films was studied using SEM. Like other LBL films, the PEG-sCT/TA films also present a rough surface 34 (Figure S2A). The thickness of an 8-bilayer film was measured to be ~20 nm.Figure 1( A ) Chemical structure of TA.…”
Peptides have great potential as therapeutic agents, however, their clinic applications are severely hampered by their instability and short circulation half-life. Zero-order release carriers could not only extend the circulation lifetime of peptides, but also maintain the plasma drug level constant, and thus maximize their therapeutic efficacy and minimize their toxic effect. Here using PEGylated salmon calcitonin (PEG-sCT)/tannic acid (TA) film as an example, we demonstrated that hydrogen-bonded layer-by-layer films of a PEGylated peptide and a polyphenol could be a platform for zero-order peptide release. The films were fabricated under mild conditions. The second component, TA, is a natural product and presents potential therapeutic activities itself. Unlike common carriers, the new carrier releases the peptide via gradual disintegration of the film because of its dynamic nature. The release of PEG-sCT follows a perfect zero-order kinetics without initial burst release. In addition the release rate could be tuned via external stimuli, such as pH and temperature. When implanted in rats, the films could remain the plasma level of PEG-sCT constant over an extended period. Accordingly, the serum calcium level was reduced and maintained constant over the same period, suggesting an improved therapeutic efficacy of the released drug.
“…The in vitro release of calcitonin from poly(ethylene glycol)-terephthalate and poly(butylene terephthalate) delivery systems was incomplete as a result of peptide aggregation caused by sodium that was used in the in vitro release test (van Dijkhuizen-Radersma et al, 2002). Three chitosan-based oral delivery systems could demonstrate prolonged release over 4 hours in vitro, but when tested in rats, only one was able to decrease significantly plasma calcium levels in a sustained manner (12 hours) (Guggi et al, 548 Kovalainen et al 2003).…”
Section: A Development Challenges Of Peptide Delivery Formulationsmentioning
“…In aqueous solutions, calcitonin has a pronounced tendency to aggregate into long, thin fibrillar aggregates, yielding a viscous and turbid dispersion (Bauer et al, 1995). A calcitonin solution stored for 20 h at room temperature also indicated the early onset of aggregation (Dijkhuizen-Radersma et al, 2002). Commercial injectable dosage forms of sCT must be formulated with suitable excipients to protect the drug in the formulation and in the biologic environment (Lee et al, 1992).…”
Peptides and polypeptides have important pharmacological properties but only a limited number have been exploited as therapeutics because of problems related to their delivery. Most of these drugs require a parenteral delivery system which introduces the problems of pain, possible infection, and expertise required to carry out an injection. The aim of this study was to develop a transdermal patch containing microneedles (MNs) coated with a peptide drug, salmon calcitonin (sCT), as an alternative to traditional subcutaneous and nasal delivery routes. Quantitative analysis of sCT after coating and drying onto microneedles was performed with a validated HPLC method. In vivo studies were carried out on hairless rats and serum levels of sCT were determined by ELISA. The AUC value of MNs coated with a trehalose-containing formulation (250 ± 83 ng/mL.min) was not significantly different as compared to subcutaneous injections (403 ± 253 ng/mL.min), but approximately 13 times higher than nasal administration (18.4 ± 14.5 ng/mL.min). Tmax (7.5 ± 5 min) values for MN mediated administration were 50% shorter than subcutaneous injections (15 min), possibly due to rapid sCT dissolution and absorption by dermal capillaries. These results suggest that with further optimization of coating formulations, microneedles may enable administration of sCT and other peptides without the need for hypodermic injections.
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