HA–EDA–Pt(iv) nanoconjugates were constructed, characterized, and proved as an safe formulation with better blood compatibility and less systemic toxicity.
Ganciclovir (GCV) is one of the most widely used antiviral drugs for the treatment of cytomegalovirus (CMV) retinitis. In this context, the aim of this study was to design in situ thermosensitive hydrogels for GCV ocular delivery by intravitreal injection to achieve sustained drug release behavior and improved ocular bioavailability in the treatment of CMV retinitis. A thermosensitive poly-(β-butyrolactone-co-lactic acid)-polyethylene glycol-poly (β-butyrolactone-co-lactic acid) (PBLA-PEG-PBLA) triblock copolymer was synthesized by ring-opening polymerization and characterization. The GCV-loaded PBLA-PEG-PBLA in situ hydrogels (15%, w/w) were then prepared with drug concentration at 2 mg·mL−1 and the gelation temperatures, rheological properties, in vitro degradation and syringeability of in situ hydrogels for intravitreal injection were also investigated. Membraneless dissolution model was used to explore drug release behavior of PBLA-PEG-PBLA in situ hydrogel. The results indicated that more than 45 and 85% of GCV can be released within 24 and 96 h, respectively, which was verified by a non-Fickian diffusion mechanism. In vivo ocular pharmacokinetics study showed that area under drug-time curve (AUC) and half-life of PBLA-PEG-PBLA in situ hydrogel was higher (AUC was 61.80 μg·mL−1·h (p < .01) and t
1/2 was 10.29 h in aqueous humor; AUC was 1008.66 μg·mL−1·h (p < .01) and t
1/2 was 13.26 h (p < .01) in vitreous) than GCV injection with extended therapeutic activity. Based on obtained results, it was concluded that the thermosenstive PBLA-PEG-PBLA in situ hydrogel is a promising carrier of GCV for intravitreal injection.
As the essential components in formulations, pharmaceutical excipients directly affect the safety, efficacy, and stability of drugs. Recently, safety incidents of pharmaceutical excipients posing seriously threats to the patients highlight the necessity of controlling the potential risks. Hence, it is indispensable for the industry to establish an effective risk assessment system of supply chain. In this study, an AHP-fuzzy comprehensive evaluation model was developed based on the analytic hierarchy process and fuzzy mathematical theory, which quantitatively assessed the risks of supply chain. Taking polysorbate 80 as the example for model analysis, it was concluded that polysorbate 80 for injection use is a high-risk ingredient in the supply chain compared to that for oral use to achieve safety application in clinic, thus measures should be taken to control and minimize those risks.
Purpose: With the increase of population aging and the proportion of overweight and obese, a growing number of people are suffering from diabetes. Insulin (INS) as the most widely used hypoglycemic agent was always chosen as the most effective treatment method of diabetes. In this study, fumaryl diketopiperazine (FDKP) was used as a carrier for the pulmonary delivery of insulin. Patients and methods: The INS-loaded FDKP microspheres (INS@FDKP-MPs) were prepared by spray drying and physicochemical properties (drug loading, particle size, flowability, moisture content, morphology, and crystalline state) were further investigated. Pharmacodynamics was investigated on diabetic model rats administrated by intratracheal insufflation. Results: The INS-loaded FDKP microspheres show satisfied flowability and in vitro deposition with FPF 50.2% and MMAD 3.45 ± 0.13 lm, and the blood glucose level was significantly decreased. Moreover, no inflammatory reaction was observed during the safety study. Conclusion: To sum up, the aim was to develop a non-injection system for insulin, INS@FDKP-MPs powder inhalation with high dose, low toxicity, and good lung deposition inhalation could rapidly decrease the blood glucose level without immune stimulation, which shows remarkably potential on diabetes treatment by pulmonary delivery route.
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