Polymeric microparticles (MPs) are recognized as very popular carriers to increase the bioavailability and bio-distribution of both lipophilic and hydrophilic drugs. Among different kinds of polymers, poly-(lactic-co-glycolic acid) (PLGA) is one of the most accepted materials for this purpose, because of its biodegradability (due to the presence of ester linkages that are degraded by hydrolysis in aqueous environments) and safety (PLGA is a Food and Drug Administration (FDA)-approved compound). Moreover, its biodegradability depends on the number of glycolide units present in the structure, indeed, lower glycol content results in an increased degradation time and conversely a higher monomer unit number results in a decreased time. Due to this feature, it is possible to design and fabricate MPs with a programmable and time-controlled drug release. Many approaches and procedures can be used to prepare MPs. The chosen fabrication methodology influences size, stability, entrapment efficiency, and MPs release kinetics. For example, lipophilic drugs as chemotherapeutic agents (doxorubicin), anti-inflammatory non-steroidal (indomethacin), and nutraceuticals (curcumin) were successfully encapsulated in MPs prepared by single emulsion technique, while water-soluble compounds, such as aptamer, peptides and proteins, involved the use of double emulsion systems to provide a hydrophilic compartment and prevent molecular degradation. The purpose of this review is to provide an overview about the preparation and characterization of drug-loaded PLGA MPs obtained by single, double emulsion and microfluidic techniques, and their current applications in the pharmaceutical industry.Graphic abstract

The growing demand for patient-compliance therapies in recent years has led to the development of transdermal drug delivery, which possesses several advantages compared with conventional methods. Delivering protein through the skin by transdermal patches is extremely difficult due to the presence of the stratum corneum which restricts the application to lipophilic drugs with relatively low molecular weight. To overcome these limitations, microneedle (MN) patches, consisting of micro/miniature-sized needles, are a promising tool to perforate the stratum corneum and to release drugs and proteins into the dermis following a non-invasive route. This review investigates the fabrication methods, protein delivery, and translational considerations for the industrial scaling-up of polymeric MNs for dermal protein delivery.

Transdermal drug delivery represents an appealing alternative to conventional drug administration systems. In fact, due to their high patient compliance, the development of dissolvable and biodegradable polymer microneedles has recently attracted great attention. Although stamp-based procedures guarantee high tip resolution and reproducibility, they have long processing times, low levels of system engineering, are a source of possible contaminants, and thermo-sensitive drugs cannot be used in conjunction with them. In this work, a novel stamp-based microneedle fabrication method is proposed. It provides a rapid room-temperature production of multi-compartmental biodegradable polymeric microneedles for controlled intradermal drug release. Solvent casting was carried out for only a few minutes and produced a short dissolvable tip made of polyvinylpyrrolidone (PVP). The rest of the stamp was then filled with degradable poly(lactide-co-glycolide) (PLGA) microparticles (μPs) quickly compacted with a vapor-assisted plasticization. The outcome was an array of microneedles with tunable release. The ability of the resulting microneedles to indent was assessed using pig cadaver skin. Controlled intradermal delivery was demonstrated by loading both the tip and the body of the microneedles with model therapeutics; POXA1b laccase from Pleurotus ostreatus is a commercial enzyme used for the whitening of skin spots. The action and indentation of the enzyme-loaded microneedle action were assessed in an in vitro skin model and this highlighted their ability to control the kinetic release of the encapsulated compound.

Doxorubicin is a highly active antineoplastic agent, but its clinical use is limited because of its cardiotoxicity. Although nutraceuticals endowed with anti-inflammatory properties exert cardioprotective activity, their bioavailability and stability are inconsistent. In an attempt to address this issue, we evaluated whether bioavailable nanoemulsions loaded with nutraceuticals (curcumin and fresh and dry tomato extracts rich in lycopene) protect cardiomyoblasts (H9C2 cells) from doxorubicin-induced toxicity. Nanoemulsions were produced with a high-pressure homogenizer. H9C2 cells were incubated with nanoemulsions loaded with different nutraceuticals alone or in combination with doxorubicin. Cell viability was evaluated with a modified MTT method. The levels of the lipid peroxidation products malondialdehyde (MDA) and 4-hydroxy-2-butanone (4-HNA), and of the cardiotoxic-related interleukins IL-6, IL-8, IL-1β and IL-10, tumor necrosis factor-alpha (TNF-α), and nitric oxide were analyzed in cardiomyoblasts. The hydrodynamic size of nanoemulsions was around 100 nm. Cell viability enhancement was 35–40% higher in cardiomyoblasts treated with nanoemulsion + doxorubicin than in cardiomyoblasts treated with doxorubicin alone. Nanoemulsions also protected against oxidative stress as witnessed by a reduction of MDA and 4-HNA. Notably, nanoemulsions inhibited the release of IL-6, IL-8, IL-1β, TNF-α and nitric oxide by around 35–40% and increased IL-10 production by 25–27% versus cells not treated with emulsions. Of the nutraceuticals evaluated, lycopene-rich nanoemulsions had the best cardioprotective profile. In conclusion, nanoemulsions loaded with the nutraceuticals described herein protect against cardiotoxicity, by reducing inflammation and lipid oxidative stress. These results set the stage for studies in preclinical models.