Rubiana Mara Mainardes

Pharmacokinetics of curcumin-loaded PLGA and PLGA-PEG blend nanoparticles after oral administration in rats.

The aim of this study was to assess the potential of nanoparticles to improve the pharmacokinetics of curcumin, with a primary goal of enhancing its bioavailability. Polylactic-co-glycolic acid (PLGA) and PLGA-polyethylene glycol (PEG) (PLGA-PEG) blend nanoparticles containing curcumin were obtained by a single-emulsion solvent-evaporation technique, resulting in particles size smaller than 200 nm. The encapsulation efficiency was over 70% for both formulations. The in vitro release study showed that curcumin was released more slowly from the PLGA nanoparticles than from the PLGA-PEG nanoparticles. A LC-MS/MS method was developed and validated to quantify curcumin in rat plasma. The nanoparticles were orally administered at a single dose in rats, and the pharmacokinetic parameters were evaluated and compared with the curcumin aqueous suspension. It was observed that both nanoparticles formulations were able to sustain the curcumin delivery over time, but greater efficiency was obtained with the PLGA-PEG nanoparticles, which showed better results in all of the pharmacokinetic parameters analyzed. The PLGA and PLGA-PEG nanoparticles increased the curcumin mean half-life in approximately 4 and 6h, respectively, and the C(max) of curcumin increased 2.9- and 7.4-fold, respectively. The distribution and metabolism of curcumin decreased when it was carried by nanoparticles, particularly PLGA-PEG nanoparticles. The bioavailability of curcumin-loaded PLGA-PEG nanoparticles was 3.5-fold greater than the curcumin from PLGA nanoparticles. Compared to the curcumin aqueous suspension, the PLGA and PLGA-PEG nanoparticles increased the curcumin bioavailability by 15.6- and 55.4-fold, respectively. These results suggest that PLGA and, in particular, PLGA-PEG blend nanoparticles are potential carriers for the oral delivery of curcumin.

Colloidal Carriers for Ophthalmic Drug Delivery

To achieve effective drug concentration at the intended site for a sufficient period of time is a requisite desired for many drug formulations. For drugs intended to ocular delivery, its poor bioavailability is due to pre-corneal factors. Most ocular diseases are treated by topical drug application in the form of solution, suspension and ointment. However, such dosage forms are no longer sufficient to combat some ocular diseases. Intravitreal drug injection is the current therapy for disorders in posterior segment. The procedure is associated with a high risk of complications, particularly when frequent, repeated injections are required. Thus, sustained-release technologies are being proposed, and the benefits of using colloidal carriers in intravitreal injections are currently under investigation for posterior drug delivery. This review will discuss recent progress and specific development issues relating to colloidal drug delivery systems, such as liposomes, niosomes, nanoparticles, and microemulsions in ocular drug delivery.

Zidovudine-loaded PLA and PLA–PEG blend nanoparticles: Influence of polymer type on phagocytic uptake by polymorphonuclear cells

Mononuclear (macrophages) and polymorphonuclear leucocytes cells play an important role in the immunopathogenesis of acquired immunodeficiency syndrome. Zidovudine is a broad-spectrum drug used in current antiretroviral therapy. The development of controlled drug delivery systems for the treatment of chronic diseases is of great interest since these systems can act as vectors, carrying the drug only to the target, and the adverse effects can be reduced. In this study, PLA and PLA/PEG blend nanoparticles containing zidovudine were developed and their uptake by polymorphonuclear leucocytes were studied in vitro. The influence of polymer type on particle size, Zeta potential and particle uptake by polymorphonuclear leucocytes was investigated. The cells were isolated from rat peritoneal exudate and their activation by nanoparticles was measured by luminol-dependent chemiluminescence and microscopical analysis. The PEG in the blend modified the Zeta potential suggested the formation of a PEG coat on the particle surface. The phagocytosis depended on the PEG and its ratio in the blend, the results showed that the PLA nanoparticles were more efficiently phagocytosed than PLA/PEG blends. The blend with the highest PEG proportion did not prevent phagocytosis, indicating that the steric effect of PEG was concentration dependent.

Liposomes and Micro/Nanoparticles as Colloidal Carriers for Nasal Drug Delivery

The use of the nasal route for drug delivery has attracted much interest in recent years in the pharmaceutical field. Local and principally systemic drug delivery can be achieved by this route of administration. But the nasal route of delivery is not applicable to all drugs. Polar drugs and some macromolecules are not absorbed in sufficient concentration due to poor membrane permeability, rapid clearance and enzymatic degradation into the nasal cavity. Thus, alternative means that help overcome these nasal barriers are currently in development. Absorption enhancers such as phospholipids and surfactants are constantly used, but care must be taken in relation to their concentration. Drug delivery systems including liposomes, cyclodextrins, micro- and nanoparticles are being investigated to increase the bioavailability of drugs delivered intranasally. This review article discusses recent progress and specific development issues relating to colloidal drug delivery systems in nasal drug delivery.

Thermoanalytical study of praziquantel-loaded PLGA nanoparticles

Polymeric nanoparticles have received great attention as potential controlled drug delivery systems. Biodegradable polymers has been extensively used in the development of these drug carriers, and the polyesters such as polylactic acid, polyglycolic acid and their copolymers as poly-lactide-co-glycolide are the most used, considering its biocompatibility and biodegradability. Thermal analysis techniques have been used for pharmaceutical substances for more than 30 years and are routine methods for screening drug-excipient interactions. The aim of this work is to use thermal analysis to characterize PLGA nanoparticles containing a hydrophobic drug, praziquantel. The results show that the drug is in an amorphous state or in disordered crystalline phase of molecular dispersion in the PLGA polymeric matrix and that the microencapsulation process did not interfere with the chemical structure of the polymer, mantaining the structural drug integrity.

PHBV/PCL Microparticles for Controlled Release of Resveratrol: Physicochemical Characterization, Antioxidant Potential, and Effect on Hemolysis of Human Erythrocytes

Microparticles of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) and poly(ε-caprolactone) (PCL) containing resveratrol were successfully prepared by simple emulsion/solvent evaporation. All formulations showed suitable encapsulation efficiency values higher than 80%. PHBV microparticles revealed spherical shape with rough surface and presence of pores. PCL microparticles were spherically shaped with smooth surface. Fourier-transformed infrared spectra demonstrated no chemical bond between resveratrol and polymers. X-ray powder diffraction patterns and differential scanning calorimetry analyses indicated that microencapsulation led to drug amorphization. These PHBV/PCL microparticles delayed the dissolution profile of resveratrol. Release profiles were better fitted to biexponential equation. The hypochlorous-acid-scavenging activity and 2,2-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) radical cation discoloration assay confirmed that the antioxidant activity of PHBV/PCL microparticles was kept, but was dependent on the microparticle morphology and dissolution profile. Resveratrol-loaded PHBV/PCL microparticles showed no cytotoxic effect on red blood cells.

Intranasal delivery of zidovudine by PLA and PLA–PEG blend nanoparticles

This study describes the preparation and evaluation of biodegradable poly(l-lactide) (PLA) and poly(l-lactide)-poly(ethylene glycol) (PLA-PEG) blend nanoparticles containing zidovudine as model drug. The prepared nanoparticles were characterized in terms of size, zeta potential, morphology and drug entrapment efficiency. The pharmacokinetics of zidovudine following intranasal administration in mice was assessed. The results showed that although PLA and blend nanoparticles had the same morphology, the particle size and zeta potential were changed by the PEG. The drug entrapment efficiency was increased by PEG presence. The pharmacokinetic study showed that all the nanoparticles were able to sustain zidovudine delivery over time, but greater efficiency was obtained with PLA-PEG blend nanoparticles, whose T(max) was twice that of PLA nanoparticles. The PLA and PLA-PEG nanoparticles formulations increased the zidovudine mean half-life by approximately 5.5 and 7h, respectively, compared to zidovudine aqueous solution. The relative bioavailability of zidovudine-loaded PLA-PEG blend nanoparticles was 2.7, relative to zidovudine-loaded PLA nanoparticles and 1.3 relative to aqueous solution formulation. Thus, the PLA nanoparticles were unable to increase the zidovudine bioavailability compared to aqueous solution formulation. The results obtained in this study indicate the potential of the PLA-PEG blend nanoparticles as carriers for zidovudine delivery by the intranasal route.

Improved neuroprotective effects of resveratrol-loaded polysorbate 80-coated poly(lactide) nanoparticles in MPTP-induced Parkinsonism.

AIM This study investigated the neuroprotective effects of resveratrol (RVT)-loaded polysorbate 80 (PS80)-coated poly(lactide) nanoparticles in a mouse model of Parkinsons disease (PD), and compared these effects with those from bulk RVT. METHODS C57BL/6 mice received for 15 days RVT intraperitoneally (nanoparticulate or non-nanoparticulate), as well as single intranasal administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a neurotoxin that damages dopaminergic neurons and induces PD-related symptoms. RESULTS MPTP induced significant impairments on olfactory discrimination and social recognition memory, as well as caused striatal oxidative stress and reduced the expression of tyrosine hydroxylase in striatum. RVT-loaded nanoparticles (but not bulk) displayed significant neuroprotection against MPTP-induced behavioral and neurochemical changes. CONCLUSION These results point to RVT-loaded poly(lactide)-nanoparticles coated with PS80 a promising nanomedical tool and adjuvant therapy for PD.

Tamoxifen-loaded poly(L-lactide) nanoparticles: Development, characterization and in vitro evaluation of cytotoxicity.

In this study, poly(L-lactide) (PLA) nanoparticles containing Tamoxifen (Tmx) were developed using an emulsion/solvent evaporation method, observing the influence of surfactants and their concentrations on mean particle size and drug entrapment. Nanoparticles were characterized in terms of size, morphology, polydispersity, interaction drug-polymer and in vitro drug release profile. Cytotoxicity over erythrocytes and tumor cells was assessed. The optimized formulation employed as surfactant 1% polyvinyl alcohol. Mean particle size was 155±4 nm (n=3) and Tmx encapsulation efficiency was 85±8% (n=3). The in vitro release profile revealed a biphasic release pattern diffusion-controlled with approximately 24% of drug released in 24 h followed by a sustained release up to 120 h (30% of Tmx released). PLA nanoparticles containing Tmx presented a very low index of hemolysis (less than 10%), in contrast to free Tmx that was significantly hemolytic. Tmx-loaded PLA nanoparticles showed IC50 value 2-fold higher than free Tmx, but considering the prolonged Tmx release from nanoparticles, cytotoxicity on tumor cells was maintained after nanoencapsulation. Thus, PLA nanoparticles are promising carriers for controlled delivery of Tmx with potential application in cancer treatment.

Colloidal polymeric nanoparticles and brain drug delivery.

The blood brain barrier protects the brain from harmful substances in the blood stream and has stopped the development of many powerful and interesting drugs candidates for central nervous system due to the low poor distribution and by efflux mechanisms. Many different approaches have been developed in order to overcome this barrier and the drug gain access to the brain. The polymeric nanoparticles are efficient colloidal systems that have been investigated to the brain drug delivery. This review will focus on the current strategies for brain drug delivery emphasizing the properties and characteristics of polymeric nanoparticles for this purpose.