Inflammation-Targeted Drug Delivery Strategies via Albumin-Based Systems.

Albumin, being the most abundant serum protein, has the potential to significantly enhance the physicochemical properties of therapeutic payloads, thereby improving their pharmacological effects. Apart from its passive transport via the enhanced permeability and retention effect, albumin can actively accumulate in tumor microenvironments or inflammatory tissues via receptor-mediated processes. This unique property makes albumin a promising scaffold for targeted drug delivery. This review focuses on exploring different delivery strategies that combine albumin with drug payloads to achieve targeted therapy for inflammatory diseases. Also, albumin-derived therapeutic products on the market or undergoing clinical trials in the past decade have been summarized to gain insight into the future development of albumin-based drug delivery systems. Given the involvement of inflammation in numerous diseases, drug delivery systems utilizing albumin demonstrate remarkable advantages, including enhanced properties, improved in vivo behavior and efficacy. Albumin-based drug delivery systems have been demonstrated in clinical trials, while more advanced strategies for improving the capacity of drug delivery systems with the help of albumin remain to be discovered. This could pave the way for biomedical applications in more effective and precise treatments.

An Albumin-Enriched Nanocomplex Achieves Systemic Delivery of Clopidogrel Bisulfate to Ameliorate Renal Ischemia Reperfusion Injury in Rats.

Herein, an albumin-enriched nanocomplex was developed for the solubilization and intravascular administration of clopidogrel bisulfate (CLP). In particular, CLP nanoparticles (HS-CLP-NPs) were synthesized via an improved nab-technology method using Solutol HS-15, and bovine serum albumin (BSA) was further enriched on the nanoparticle surface forming a protein corona (BH-CLP-NPs). BH-CLP-NPs displayed an average size of 163.4 ± 10.5 nm, a zeta potential of 1.85 ± 0.03 mV, an encapsulation efficiency of 99.9%, and a drug loading capacity of 32.9%. The cumulative release of CLP from BH-CLP-NPs reached about 60% within 168 h. The pharmacokinetic study on the CLP metabolite indicated that the BSA-enriched nanoparticle showed greater in vivo exposure. Pharmacodynamic studies in the renal ischemia/reperfusion injury rat model further demonstrated the renal protective effect of systemically administered BH-CLP-NPs against acute kidney injury with significantly downregulated blood urea nitrogen and creatinine levels. Overall, the albumin-enriched nanocomplexes offer a neat and efficient strategy for the development of poorly water-soluble drugs to achieve intravascular administration.

[Preparation and Characterization of Clopidogrel Bisulfate Liposomes].

OBJECTIVE: To prepare encapsulated clopidogrel bisulfate (CLP) liposomes so as to deal with the poor water solubility of CLP, and to provide the experimental basis for the development of CLP formulations for intravascular injection. METHODS: CLP-loaded liposomes were prepared using thin film hydration/sonication method and pH gradient active drug loading technology. Then, the morphology, particle size, encapsulation efficiency, drug loading capacity, Zeta potentials and in vitro release behavior were characterized. Bilateral renal arteries of Sprague-Dawley (SD) rats were clamped with micro-artery clamps to establish the model of renal ischemia-reperfusion injury (IRI) in male SD rats. The study aimed to preliminarily investigate the therapeutic effect of CLP-loaded liposome pretreatment on renal IRI in rats. RESULTS: It was found that the optimal formulation and preparation technology of CLP liposomes were as follows: the CLP-to-phospholipid weight ratio of 1∶10, phospholipid-to-cholesterol ratio of 6∶1, octadecylamine-to-CLP ratio of 1.2∶1, PEG 400-to-CLP ratio of 1∶1, and incubation at 50 ℃ for 40 min. Then, following ultrasonication of 100 W efficiency at 5-second intervals for 20 times, CLP loading was conducted using 5 mL of 0.1 mol/L citric acid buffer at pH 3.0. Liposome samples were prepared with the film dispersion method, and the pH value was adjusted to 7.5 through pH gradient active drug loading technology. The CLP-loaded liposomes obtained in this way had a rounded shape, good dispersity, an average particle size of (134.13±2.60) nm, polydispersity index (PDI) of 0.25±0.02, and a Zeta potential of (2.12±0.23) mV. The encapsulation efficiency was found to be (98.66±0.14)%, and the drug loading capacity was (7.47±0.01)%. The in vitro release results showed that 66.24% of CLP was released cumulatively within 72 h. Preliminary efficacy experiments showed that animals pretreated with CLP-loaded liposomes had lower serum levels of blood urea nitrogen and creatinine compared to the levels of IRI model rats without any pretreatment. CONCLUSION: CLP-loaded liposomes were successfully prepared, which might provide the experimental foundation for the future development of CLP formulations for injection.

Engineered PLGA microspheres for extended release of brexpiprazole: in vitro and in vivo studies.

OBJECTIVE: To develop poly(d,l-lactide-co-glycolide) (PLGA) microspheres to achieve controlled and sustained release of brexpiprazole in vivo. METHODS: Brexpiprazole microspheres were prepared by oil-in-water emulsion-solvent evaporation method and evaluated for morphology, particle size, encapsulation efficiency, drug loading, conformation and compatibility of drug and polymer, in vitro release, and in vivo pharmacokinetics. By establishing the relationship between in vitro and in vivo release, it helps identify the appropriate in vitro release conditions to explore release profiles of brexpiprazole microspheres. RESULTS: Porous PLGA microspheres with near spherical morphology were obtained displaying an average diameter of 20.43 ± 0.06 µm, a drug loading capacity of 27.24 ± 0.33% and an encapsulation efficiency of 81.87 ± 1.07%. Fourier transform infrared spectroscopy (FTIR), powder X-ray diffraction (PXRD), and differential scanning calorimetry (DSC) analysis showed that some drugs encapsulated in the microspheres remained in the amorphous state and some were in the crystalline state. Different release setups resulted in different release kinetics. The dialysis release setup displayed a cumulative release of about 65% within 60 days, while the sample-and-separate setup showed a cumulative release of about 77% within 35 days. Per pharmacokinetic studies in rats, a burst phase in the plasma concentration-time curve was observed after intramuscular injection in the first 2 h followed by a clear zero-order release phase. Overall, brexpiprazole achieved in vivo sustained release from PLGA microspheres for up to 40 days. CONCLUSION: A PLGA microsphere loaded with brexpiprazole was successfully developed and demonstrated potential for extended-release of therapeutics for schizophrenia treatment.