Peptide Acylation in Aliphatic Polyesters: a Review of Mechanisms and Inhibition Strategies.

Biodegradable polyesters are widely employed in the development of controlled release systems for peptide drugs. However, one of the challenges in developing a polyester-based delivery system for peptides is the acylation reaction between peptides and polymers. Peptide acylation is an important factor that affects formulation stability and can occur during storage, in vitro release, and after drug administration. This review focuses on the mechanisms and parameters that influence the rate of peptide acylation within polyesters. Furthermore, it discusses reported strategies to minimize the acylation reaction.

Design of experiments approach for the development of a validated method to determine the exenatide content in poly(lactide-co-glycolide) microspheres.

Due to the lack of pharmacopeia guidelines for injectable microspheres based on poly (D, L-lactide-co-glycolide) (PLGA), an internal method validation is a critical prerequisite for quality assurance. One of the essential issues of developing peptide-based drugs loaded PLGA microspheres is the precise determination of the amount of peptide drug entrapped in the microspheres. The aim of this study is the development and optimization of a method for measuring the drug content loading of PLGA microspheres using exenatide as a model peptide drug. Exenatide-loaded PLGA microspheres were prepared by a double emulsion solvent evaporation method. The extraction method to determine exenatide content in microspheres was optimized using Design of Experiments (DoE) approach. After the initial screening of six factors, using Fractional Factorial design (FFD), four of them, including type of organic solvent, buffer/organic solvent ratio (v/v), shaking time and pH, exhibited significant effects on the response, namely the exenatide loading, and a Box-Behnken design (BBD) was subsequently applied to obtain its optimum level. The optimum level for organic solvent volume, buffer/organic solvent ratio, shaking time, and pH were 4 ml, 1, 5.6 hrs, and pH 6, respectively. The exenatide content in microspheres under these conditions was 6.4 ± 0.0 (%w/w), whereas a value of 6.1% was predicted by the derived equation. This excellent agreement between the actual and the predicted value demonstrates that the fitted model can thus be used to determine the exenatide content.

Recent progress in the intranasal PLGA-based drug delivery for neurodegenerative diseases treatment.

One of the most challenging problems of the current treatments of neurodegenerative diseases is related to the permeation and access of most therapeutic agents to the central nervous system (CNS), prevented by the blood-brain barrier (BBB). Recently, intranasal (IN) delivery has opened new prospects because it directly delivers drugs for neurological diseases into the brain via the olfactory route. Recently, PLGA-based nanocarriers have attracted a lot of interest for IN delivery of drugs. This review gathered clear and concise statements of the recent progress of the various developed PLGA-based nanocarriers for IN drug delivery in brain diseases including Alzheimer's, Parkinson's, brain tumors, ischemia, epilepsy, depression, and schizophrenia. Subsequently, future perspectives and challenges of PLGA-based IN administration are discussed briefly.

Effect of Topical Furosemide Efficacy on Reducing Bleeding and Quality of Surgical Field During Endoscopic Sinus Surgery in Patients with Chronic Rhinosinusitis.

Introduction: Bleeding during endoscopic sinus surgery has an unfavorable effect on the surgical field and prolongs the time of surgery. In this study, we assessed the efficacy of topical furosemide on bleeding and the quality of the surgical field during endoscopic sinus surgery. Materials and Methods: In this clinical trial, 76 patients with chronic rhinosinusitis were selected for endoscopic sinus surgery and randomly assigned to two groups, topical furosemide (intervention) and normal saline (control). The intervention group received 20 micrograms of intranasal spray twice daily, and the control group received regular intranasal saline spray, similar to the intervention group. In addition, the quality of the surgical field (scoring by the BOEZAART grading system) and the amount of bleeding during surgeries were measured. All data were analyzed. Results: In the intervention and control groups, the mean surgical bleeding volume was 187.70± 24.79 and 229.21± 28.18 ml (P <0.001), the mean of Boezaart scale 2 and 3 (P <0.001) and the mean of surgical time were 106.53±14.67 and 126.63 ± 15.42 minutes (P <0.001), respectively. In patients of the intervention group with and without polyps, the mean surgery time was 99.56± 12.15 and 118.84 ±10.03 minutes (P <0.001), and the mean bleeding volume during endoscopic sinus surgery was 176.46 ± 22.58, 208.46 ±12.14 ml (P <0.001) respectively. Conclusions: Our findings showed that nasal, topical furosemide spray significantly reduced the amount of bleeding during endoscopic sinus surgery and time of the surgery and improved the quality of the surgical field.

Effect of Topical Furosemide on Rhinosinusal Polyposis Relapse After Endoscopic Sinus Surgery: A Randomized Clinical Trial.

Importance: Evidence from previous studies suggests that furosemide may be effective in reducing the recurrence of polyps after sinus surgery. However, the evidence is limited and insufficient, and further investigations are required. Objective: To assess the effect of topical furosemide on recurrence rate of rhinosinusal polyposis after endoscopic sinus surgery. Design, Setting, and Participants: Triple-blind randomized clinical trial of patients aged 18 to 60 years with chronic rhinosinusitis associated with polyposis who did not respond to medical treatment and were candidates for endoscopic sinus surgery at Besat Hospital, Hamadan University of Medical Sciences, from April 2014 to June 2015. Interventions: Patients were randomly assigned to receive postoperative nasal spray, 2 puffs twice a day for 2 months, either 300 µg of furosemide per day or placebo. Main Outcomes and Measures: Six months after surgery, the patients were examined for nasal and paranasal sinus polyposis using Meltzer endoscopic grading, computed tomographic (CT) scan of paranasal sinuses (PNS) scoring, Sino-Nasal Outcome Test (SNOT-22) scoring, and visual analog scale (VAS). Results: Of 110 patients enrolled, 84 patients remained for analysis (53 men and 31 women; mean age in the furosemide group, 37.02 years, range, 18-58 years; mean age in the placebo group, 36.30 years, range, 18-60 years). Six months after the intervention, the grade of polyposis decreased in both groups, but this reduction was substantial in the furosemide group vs the placebo group. The severity of polyposis was significantly lower in the furosemide group vs the placebo group based on SNOT-22 scoring (difference, 8.05; 95% CI, 3.24-12.85) and VAS (difference, 0.81; 95% CI, 0.22-1.39) but not significantly different based on CT scan of PNS scoring (difference, 2.52; 95% CI, -0.35 to 5.39). The incidence of adverse effects (nasal irritation, headache, and constipation) were not significantly different between the 2 groups. Conclusions and Relevance: These findings indicate that topical furosemide is a safe drug, with no important adverse effects, that can substantially reduce the severity of polyposis after endoscopic sinus surgery. Trial Registration: Iranian Registry of Clinical Trials registration number: IRCT201403143186N5.