Formulation of venlafaxine for once daily administration using polymeric material hybrids.

OBJECTIVE: Controlled release venlafaxine for once daily administration. METHODS: Drug resin complexation followed by polymer encapsulation. A 4(1).2(1) factorial design was used to study the effect of polymer type and core: coat ratio on the release profile and kinetics. Polymer combinations were tried for optimisation adapting the desIMNCility function. The optimised formula was tested in rabbits against commercial extended release capsules. RESULTS: Poly-epsilon-caprolactone, poly(d, l-lactide-co-glycolide) ester and poly(d, l-lactide) ester polymers were more efficient in lowering the release rate and the initial burst release than Eudragit(®)RS100. Encapsulation at 1:1 ratio ensured complete coats and drug release sustainment. Formula prepared using 50:50 PLA/Eudragit at 1:1 ratio sustained the drug release up to 24 h with low burst release. This formula had higher venlafaxine absorption in rabbits compared to the commercial capsules. CONCLUSIONS: The optimised formula is superior to the available once-daily trials regarding enhanced bioavailability, dosage form versatility and ease of scaling up.

Synthesis, characterisation and drug release properties of microspheres of polystyrene with aliphatic polyester side-chains.

A series of graft copolymers consisting of polystyrene backbone with biocompatible side chains based on (co)polymers of l-lactic acid and glycolic acid were synthesised by combination two controlled polymerisations, namely, nitroxide mediated radical polymerisation (NMRP) and ring opening polymerisation (ROP) with "Click" chemistry. The main goal of this work was to design new biodegradable microspheres using obtained graft copolymers for long-term sustained release of imatinib mesylate (IMM) as a model drug. The IMM loaded microspheres of the graft copolymers, polystyrene-g-poly(lactide-co-glycolide) (PS-g-PLLGA), polystyrene-g-poly(lactic acid) (PS-g-PLLA) and poly(lactic-coglycolic acid) (PLLGA) were then prepared by a modified water-in-oil-in-water (w1/o/w2) double emulsion/solvent evaporation technique. The optimised microspheres were characterised by particle size, encapsulation efficiency, and surface morphology also; their degradation and release properties were studied in vitro. The degradation studies of three different types of microspheres showed that the PS backbone of the graft copolymers slows down the degradation rate compared to PLLGA.

Preparation and in vitro evaluation of surface-modified poly (lactide-co-glycolide) microparticles as biodegradable drug carriers for pulmonary peptide and protein delivery.

The present study reports the preparation and physicochemical characterization of surface-modified poly(lactide-co-glycolide) (PLGA) microparticles containing interleukin-2 (rhIL-2) for pulmonary delivery. The surface of the microparticles was modified with mucoadhesive polymers such as chitosan and Carbopol 971P. The feasibility of this surface modification was confirmed by measuring the zeta potential. Chitosan-modified PLGA microparticles showed a positive zeta potential, while Carbopol-modified PLGA microparticles were negatively charged. The mucin binding efficiency values have shown that the positively charged chitosan coated microparticles showed a higher adhesive percent to the mucin than the negatively charged un-coated or Carbopol 971P coated microparticles. Furthermore, surface modification of microparticles with chitosan and Carbopol 971P has yielded a slight decrease in the amount of protein initially released. These findings suggest the suitability of surface-modified PLGA microparticles as an efficient carrier system for delivery peptides and proteins to the respiratory tract.

Non-aggregated protamine-coated poly(lactide-co-glycolide) nanoparticles of cisplatin crossed blood-brain barrier, enhanced drug delivery and improved therapeutic index in glioblastoma cells: in vitro studies.

BACKGROUND AND OBJECTIVES: Non-aggregated protamine impregnated poly(lactide-co-glycolide) nanoparticles of cisplatin (Pt-PLGA NPs) were synthesized to augment brain delivery. METHODS AND RESULTS: The mean particle size of Pt-PLGA NPs and PLGA NPs were observed to be 173.2 ± 7.9 nm and 140 ± 10.2 nm, respectively. The Pt-PLGA NPs significantly (p < 0.05, one-way analysis of variance; ANOVA) delivered higher amount (172.41 ± 15.04 µg) of cisplatin in comparison to 110.48 ± 4.71 µg by PLGA NPs and 20.83 ± 1.65 µg by cisplatin solution across in vitro bovine brain microvessel endothelial cells. Cisplatin bearing Pt-PLGA NPs was found to be highly cytotoxic to U87 glioblastoma cells with an IC50 of 2.1 µM as compared (one-way ANOVA, p < 0.05) to PLGA NPs (3.9 µM) and cisplatin alone (13.33 µM). Impregnation with Pt enhanced the uptake of PLGA NPs in U87 glioblastoma cells as compared to PLGA NPs by following endocytosis mechanism. CONCLUSION: Cisplatin-loaded Pt-PLGA NPs compel preclinical tumour regression study to further improve its utility against glioblastoma.

Treating colon cancer with injectable PLGA-PEG-PLGA as a carrier for iodine-125.

PURPOSE OF WORK: Provide a safer way for treating various cancers with PLGA-PEG-PLGA (PPP)-embedded iodine-125. To improve the safety of iodine treatment for colon cancer, iodine-125 solution was embedded into PLGA-PEG-PLGA (PPP) (synthesized by bulk co-polymerization of DL-polylactide glycolide and PEG). Xenograft-carrying nude mice were then treated with iodine-125-PPP. Proliferating cell nuclear antigen and Terminal Transferase dUTP Nick-End Labeling were used to measure proliferation and apoptosis in the tumors, respectively. Simultaneously, immunohistochemistry SP was used to detect the expression levels of p53. In addition, the microvessel density (MVD) of the tumors was recorded. PPP-embedded iodine-125 induced apoptosis by increasing the expression of p53, and by decreasing the levels of VEGF and MVD in the colon cancer tumors (P < 0.01). Significant inhibition of tumor growth is seen with iodine-125 from 0.4 to 0.8 mCi. PPP-embedded iodine-125 has a similar inhibitory efficiency to using the iodine-125 seeds for the treatment of colon tumors (P > 0.05). The findings therefore provide a potentially safer method for treating various tumors with radioactive iodine.

Long-circulating poly(ethylene glycol)-coated poly(lactid-co-glycolid) microcapsules as potential carriers for intravenously administered drugs.

The intrinsic advantages of microcapsules with regard to nanocapsules as intravenous drug carrier systems are still not fully exploited. Especially, in clinical situations where a long-term drug release within the vascular system is desired, if large amounts of drug have to be administered or if capillary leakage occurs, long-circulating microparticles may display a superior alternative to nanoparticles. Here, microcapsules were synthesised and parameters such as in vitro tendency of agglomeration, protein adsorption and in vivo performance were investigated. Biocompatible poly(ethylene glycol) (PEG)-coated poly(DL-lactide-co-glycolide) (PLGA) as wall material, solid and perfluorodecalin (PFD)-filled PEG-PLGA microcapsules (1.5 µm diameter) were manufactured by using a modified solvent evaporation method with either 1% poly(vinyl alcohol) (PVA) or 1.5% cholate as emulsifying agents. Compared to microcapsules manufactured with cholate, the protein adsorption (albumin and IgG) was clearly decreased and agglomeration of capsules was prevented, when PVA was used. The intravenous administration of these microcapsules, both solid and PFD-filled, in rats was successful and exhibited a circulatory half-life of about 1 h. Our data clearly demonstrate that PEG-PLGA microcapsules, manufactured by using PVA, are suitable biocompatible, long-circulating drug carriers, applicable for intravenous administration.

Capillary electrophoresis of bone marrow stromal cells with uptake of heparin-functionalized poly(lactide-co-glycolide) nanoparticles during differentiation towards neurons.

This study analyzes the varying electrophoretic mobility and zeta potential of bone marrow stromal cells (BMSCs) during their differentiation towards neurons. Electrophoresis of primary BMSCs and neuron growth factor (NGF)-induced neuron-like cells with the uptake of heparin-functionalized poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) are also investigated. Immunofluorescent images revealed that a high concentration of NGF accelerated the differentiation of BMSCs into neurons. When the concentration of NGF increased, the absolute values of electrophoretic mobility and zeta potential of the differentiating BMSCs increased. In addition, a longer inductive period yielded higher charge of the differentiating BMSCs and a smaller uptake amount of heparin-functionalized PLGA NPs. However, an increase in the loading efficiency of heparin on PLGA NPs enhanced the uptake and reduced the electrical characteristics of the primary and differentiating BMSCs. Hence, a general rule is drawn that an increase in the uptake of heparin-functionalized PLGA NPs decreased the electrophoretic mobility and zeta potential of BMSCs during differentiation towards neurons.

Effects of poloxamer 188 on the characteristics of poly(lactide-co-glycolide) nanoparticles.

We tested the effects of poloxamer 188 on the preparation and characteristics of poly(lactice-co-glycolide) (PLGA) nanoparticles containing all-trans retinoic acid (ATRA). Spherical nanoparticles incorporated ATRA were prepared by an emulsification-diffusion method increasing concentrations of poloxamer 188 decreased nanoparticle size. The endothermic peak of ATRA at 183 degrees C disappeared in the nanoparticles and X-ray diffraction measurements showed the disappearance of characteristics of ATRA suggesting the change of the crystallinity of ATRA in the nanoparticles to an amorphous state. ATRA release in vitro increased as the concentration of poloxamer increased. The mean residence time of ATRA-loaded nanoparticles after the administration of a single intravenous dose to rats was longer than that of the sodium ATRA solution. The anti-cancer activity of ATRA-loaded nanoparticles in the human leukemia-60 cell line was similar to free ATRA. Thus, PLGA/poloxamer nanoparticles can provide a sustained release preparation of ATRA.

Engineering red-emitting multi-functional nanocapsules for magnetic tumour targeting and imaging.

In this work we describe the formulation and characterisation of red-emitting polymeric nanocapsules (NCs) incorporating superparamagnetic iron oxide nanoparticles (SPIONs) for magnetic tumour targeting. The self-fluorescent oligomers were synthesised and chemically conjugated to PLGA which was confirmed by NMR spectroscopy, FT-IR spectroscopy and mass spectrometry. Hydrophobic SPIONs were synthesised through thermal decomposition and their magnetic and heating properties were assessed by SQUID magnetometry and calorimetric measurements, respectively. Magnetic nanocapsules (m-NCs) were prepared by a single emulsification/solvent evaporation method. Their in vitro cytotoxicity was examined in CT26 colon cancer cells. The formulated fluorescent m-NCs showed good stability and biocompatibility both in vitro and in vivo in CT 26 colon cancer models. Following intravenous injection, accumulation of m-NCs in tumours was observed by optical imaging. A higher iron content in the tumours exposed to a magnetic field, compared to the contralateral tumours without magnetic exposure in the same animal, further confirmed the magnetic tumour targeting in vivo. The overall results show that the engineered red-emitting m-NCs have great potential as multifunctional nanocarriers for multi-model bioimaging and magnetic-targeted drug delivery.

A thermo-responsive and self-healing liposome-in-hydrogel system as an antitubercular drug carrier for localized bone tuberculosis therapy.

Isoniazid (INH) is a first-line therapy for bone tuberculosis (TB), but its clinic benefits are limited by severe side-effects after long-time administration. While nano-drug delivery systems present as promising strategies for INH delivery, the therapeutic efficacies are usually suboptimal due to ineffective drug accumulation at diseased sites. Local delivery system can achieve high drug concentration at focus sites with minimal systemic exposure, and herein we aimed to employ this strategy to develop a novel liposome-in-hydrogel system for localized treatment of bone TB. To achieve sustainable drug release, a derivative of INH called DINH was loaded because of its hydrophobicity, as well as its better activity and higher biosafety than INH. The hybrid system was demonstrated for thermo-responsive and self-healing properties via phase transition test and rheological studies, which were particularly useful for intra-articular administration. In vivo microdialysis studies revealed that the system can rapidly release drug into synovial fluid to reach effective inhibitory concentrations after localized injection, followed by a steady-state drug release. The optical image studies were performed to study its long-term behavior in vivo, which suggested a sustained drug release profile for several days. This work provides a promising drug delivery system for bone TB therapy.

Morphological changes of poly(DI-lactide-co-glycolide) nano-particles containing ascorbic acid during in vitro degradation process.

Poly(DL-lactide-co-glycolide) powder composed of uniform particles with the mean particle size in the range of 110-170 nm was obtained from commercial granules. Ascorbic acid in different concentrations was encapsulated into the poly(DL-lactide-co-glycolide) particles. Degradation of the latter in terms of morphological changes in the physiological solution was followed. Within a period of 2 months, the particles completely degrade and all the ascorbic acid is released. The samples were characterized by ultraviolet spectroscopy and scanning electron microscopy.

Comparative study of polyglactin 910 and simple catgut in the formation of intraperitoneal adhesions.

PURPOSE: To compare polyglactin 910 and simple catgut sutures for the incidence of intraperitoneal adhesions. METHODS: Twenty female Wistar rats were placed into two groups. Group 1 received ischemic sutures and Group 2 received polyglactin 910. Five sutures inductive of adhesions in each rat were made. After 14 days, the rats were euthanized with an assessment of the presence of adhesions, the number of sutures involved and classification according to the Granat et al. scale described by Ozel et al17. RESULTS: In total, 19 of the 20 rats presented adhesions, with nine from Group 1 and ten from Group 2. There was a smaller number of affected sutures in Group 1, while in Group 2 the majority of the sutures formed adhesions (p=0.0197). According to the Granat et al. scale, Group 1 predominately developed fine, filamentous adhesions or thickening in a restricted area. Group 2 mainly presented extensive, thick adhesions with the involvement of the viscera (p=0.0055). CONCLUSION: Polyglactin 910 sutures formed more adhesions that were more extensive and thicker than the simple catgut sutures.

In situ low-immunogenic albumin-conjugating-corona guiding nanoparticles for tumor-targeting chemotherapy.

Nanoparticles (NPs) are unavoidably covered by a layer of immunogenic proteins upon injection into blood, such as immunoglobins and complements, which buries the active-targeting ligands and triggers the rapid clearance of NPs by the mononuclear phagocytic system. Low antifouling polyethylene glycol is used to inhibit the formation of the immunogenic corona but it leads to poor cellular uptake and the immunogen-related accelerated blood clearance (ABC) phenomenon in multiple administrations. Here, we develop surface maleimide-modified NPs that covalently conjugate in vivo plasma albumin in its corona upon exposure to blood. The in situ recruited low-immunogenic albumin-enriching corona is capable of protecting maleimide-decorated NPs from phagocytosis in the bloodstream, preventing the ABC phenomenon in the second administration, facilitating NP accumulation in the tumor site/cells by the passive EPR effect and albumin receptor-mediated active targeting, and finally improving the antitumor activity. Such findings suggest that the facile strategy, based on the in situ anchored albumin-enriching corona, is efficient at enabling maleimide-decorated NPs to acquire stealth and tumor-targeting ability.

Development of a non-toxic and non-denaturing formulation process for encapsulation of SDF-1α into PLGA/PEG-PLGA nanoparticles to achieve sustained release.

Chemokines are known to stimulate directed migration of cancer cells. Therefore, the strategy involving gradual chemokine release from polymeric vehicles for trapping cancer cells is of interest. In this work, the chemokine stromal cell-derived factor-1α (SDF-1α) was encapsulated into nanoparticles composed of poly-(lactic-co-glycolic acid) (PLGA) and a polyethylene glycol (PEG)-PLGA co-polymer to achieve sustained release. SDF-1α, and lysozyme as a model protein, were firstly precipitated to promote their stability upon encapsulation. A novel phase separation method utilising a non-toxic solvent in the form of isosorbide dimethyl ether was developed for the individual encapsulation of SDF-1α and lysozyme precipitates. Uniform nanoparticles of 200-250 nm in size with spherical morphologies were successfully synthesised under mild formulation conditions and conveniently freeze-dried in the presence of hydroxypropyl-ß-cyclodextrin as a stabiliser. The effect of PLGA carboxylic acid terminal capping on protein encapsulation efficiency and release rate was also explored. Following optimisation, sustained release of SDF-1α was achieved over a period of 72 h. Importantly, the novel encapsulation process was found to induce negligible protein denaturation. The obtained SDF-1α nanocarriers may be subsequently incorporated within a hydrogel or other scaffolds to establish a chemokine concentration gradient for the trapping of glioblastoma cells.

Physicochemical stability and transfection efficiency of cationic amphiphilic copolymer/pDNA polyplexes for spinal cord injury repair.

Multiple age-related and injury-induced characteristics of the adult central nervous system (CNS) pose barriers to axonal regeneration and functional recovery following injury. In situ gene therapy is a promising approach to address the limited availability of growth-promoting biomolecules at CNS injury sites. The ultimate goal of our work is to develop, a cationic amphiphilic copolymer for simultaneous delivery of drug and therapeutic nucleic acids to promote axonal regeneration and plasticity after spinal cord injury. Previously, we reported the synthesis and characterization of a cationic amphiphilic copolymer, poly (lactide-co-glycolide)-graft-polyethylenimine (PgP) and its ability to efficiently transfect cells with pDNA in the presence of serum. We also demonstrated the efficacy of PgP as a therapeutic siRhoA carrier in a rat compression spinal cord injury model. In this work, we show that PgP/pDNA polyplexes provide improved stability in the presence of competing polyanions and nuclease protection in serum relative to conventional branched polyethylenimine control. PgP/pDNA polyplexes maintain bioactivity for transfection after lyophilization/reconstitution and during storage at 4 °C for up to 5 months, important features for commercial and clinical application. We also demonstrate that PgP/pDNA polyplexes loaded with a hydrophobic fluorescent dye are retained in local neural tissue for up to 5 days and that PgP can efficiently deliver pß-Gal in a rat compression SCI model.

Ultrasound-induced mild hyperthermia improves the anticancer efficacy of both Taxol® and paclitaxel-loaded nanocapsules.

We study the influence of ultrasound on paclitaxel-loaded nanocapsules in vitro and in vivo. These nanocapsules possess a shell of poly(dl-lactide-co-glycolide)-poly(ethylene glycol) (PLGA-PEG) and a liquid core of perfluorooctyl bromide (PFOB). In vitro experiments show that mechanical effects such as cavitation are negligible for nanocapsules due to their small size and thick and rigid shell. As the mechanical effects were unable to increase paclitaxel delivery, we focused on the thermal effects of ultrasound in the in vivo studies. A focused ultrasound sequence was therefore optimized in vivo under magnetic resonance imaging guidance to obtain localized mild hyperthermia with high acoustic pressure. Ultrasound-induced mild hyperthermia (41-43°C) was then tested in vivo in a subcutaneous CT-26 colon cancer murine model. As hyperthermia is applied, an inhibition of tumor growth for both paclitaxel-loaded nanocapsules and the commercial formulation of paclitaxel, namely Taxol® have been observed (p<0.05). Ultrasound-induced mild hyperthermia at high acoustic pressure appears as an interesting strategy to enhance cytotoxic efficacy locally.

Efficacy assessment of self-assembled PLGA-PEG-PLGA nanoparticles: Correlation of nano-bio interface interactions, biodistribution, internalization and gene expression studies.

The aim of our study was to develop and compare the biological performance of two types of biodegradable SN-38 loaded nanoparticles (NPs) with various surface properties, composed of low and high Mw triblock PLGA-PEG-PLGA copolymers, applying rational quality and safety by design approach. Therefore, along with the optimization of crucial physico-chemical properties and in order to evaluate the therapeutical potential and biocompatibility of prepared polymeric nanoparticles, analysis of nano-bio interactions, cell internalization, gene expression and biodistribution studies were performed. The optimized formulations, one of low Mw and one composed of high Mw PLGA-PEG-PLGA copolymer, exhibited different characteristics in terms of surface properties, particle size, zeta potential, drug loading, protein adsorption and biodistribution, which may be attributed to the variations in nano-bio interface interactions due to different NP building blocks length and Mw. On the contrary to protein adsorption and biodistribution studies, both types of NPs exhibited similar results during cell internalization and gene expression studies performed in cell culture medium containing serum proteins. This pool of useful data for internalization and efficacy as well as the notable advance in the circulation time of low Mw NPs may be further employed for shaping the potential of the designed nanocarriers.

Impact of chromic catgut versus polyglactin 910 versus fast-absorbing polyglactin 910 sutures for perineal repair: a randomized, controlled trial.

OBJECTIVE: The goal of our study was to compare the impact of 3 suture materials on perineal pain and on resumption of sexual intercourse. STUDY DESIGN: This randomized, controlled trial compared 3 types of suture materials (chromic catgut, polyglactin 910, fast-absorbing polyglactin 910) for second-degree perineal laceration or uncomplicated episiotomy. Patients were enrolled in early labor and assigned randomly to 1 of the 3 suture materials. Pain was evaluated at 48 hours, 6 weeks, and 3 months. The study subjects were questioned about residual perineal pain, resumption of sexual activity, and pain-free sexual intercourse. Logistic regression analyses were undertaken. RESULTS: Of the 192 patients who were assigned randomly to groups, 66 patients had their perineal laceration repaired with chromic catgut; 60 patients had repair with polyglactin 910, and 66 patients had repair with fast-absorbing polyglactin 910. At 48 hours, there was no significant difference according to the pain measurement scores, but the median consumption of analgesics was significantly lower with fast-absorbing polyglactin 910 than with standard polyglactin 910. There was no difference in the resumption of sexual intercourse at 6 weeks after the delivery between chromic catgut (42%) compared with standard polyglactin 910 group (56%; P = .23). However, it was more frequent for women in the fast-absorbing polyglactin 910 group (66%; P = .02). After adjustment for confounding variables, perineal repair with fast-absorbing polyglactin 910 was associated with a higher rate of sexual intercourse (odds ratio, 2.55; 95% CI, 1.07-6.10) and a higher rate of pain-free sexual intercourse (odds ratio, 2.51; 95% CI, 1.03-6.10) at 6 weeks after delivery. CONCLUSION: Fast-absorbing polyglactin 910 for perineal repair is associated with earlier resumption of sexual intercourse when compared with chromic catgut.

Fluorescence imaging enabled poly(lactide-co-glycolide).

Fluorescent biomaterials have attracted significant research efforts in the past decades. Herein, we report a new series of biodegradable, fluorescence imaging-enabled copolymers, biodegradable photoluminescent poly(lactide-co-glycolide) (BPLP-co-PLGA). Photoluminescence characterization shows that BPLP-co-PLGA solutions, films and nanoparticles all exhibit strong, tunable and stable photoluminescence. By adjusting the molar ratios of L-lactide (LA)/glycolide (GA) and (LA+GA)/BPLP, full degradation of BPLP-co-PLGA can be achieved in 8-16 weeks. The fluorescence decay behavior of BPLP-co-PLGA can be used for non-invasive monitoring of material degradation. In vitro cytotoxicity and in vivo foreign body response evaluations demonstrate that BPLP-co-PLGA exhibits similar biocompatibility to poly(lactide-co-glycolide) (PLGA). The imaging-enabled BPLP-co-PLGA was fabricated into porous scaffolds whose degradation can be monitored through non-invasive imaging and nanoparticles that show theranostic potential demonstrated by fluorescent cellular labeling, imaging and sustained 5-fluorouracil delivery. The development of inherently fluorescent PLGA copolymers is expected to impact the use of already widely accepted PLGA polymers for applications where fluorescent properties are highly desired but limited by the conventional use of cytotoxic quantum dots and photobleaching organic dyes. STATEMENT OF SIGNIFICANCE: This manuscript describes a novel strategy of conferring intrinsic photoluminescence to the widely used biodegradable polymers, poly(lactide-co-glycolide) without introducing any cytotoxic quantum dots or photo-bleaching organic dyes, which may greatly expand the applications of these polymers in where fluorescent properties are highly desired. Given the already significant impact generated by the use of PLGA and alike, this work contributes to fluorescence chemistry and new functional biomaterial design and will potentially generate significant impact on many fields of applications such as tissue engineering, molecular imaging and labeling, and drug delivery.

Peptide-derivatized biodegradable nanoparticles able to cross the blood-brain barrier.

Injectable nanoparticulate drug carriers (Np) able to cross the blood-brain barrier (BBB) have important potential applications for the treatment of diseases that affect the central nervous system (CNS). With the aim to create a system able to address Np to the CNS, we synthesized conjugates between a biodegradable copolymer, poly(D,L-lactide-co-glycolide) (PLGA), and five short peptides, by means of an amidic linkage. These peptides, that are similar to synthetic opioid peptides, were synthesized in turn by means of Fmoc solid-phase peptide synthesis. The new five modified copolymers thus obtained turned out to be valuable starting material for the preparation of Np; these were made fluorescent, in order to allow their localization after their administration, by inclusion of a fluorescent probe. The Np thus prepared were characterized (morphology, size and z-potential) and were shown to possess the peptidic moieties on their surface, as evidenced by ESCA spectroscopy. Then, their ability to cross the BBB was assessed by the in vivo Rat Brain Perfusion Technique and, in one case, by means of a systemic administration (rat femoral vein injection). Fluorescent and confocal microscopy studies showed that while PLGA Np are unable to cross the BBB, for the first time these solid Np surface-modified with peptides were shown to be able to cross the BBB.