Surface-modified PLGA Nanoparticles Research Articles

Surface modified PLGA nanoparticles of gabapentin: Biodistribution and pharmacodynamic investigation via intranasal route

Epilepsy is a chronic condition and is caused by abnormal electrical conduction by nerve cells. It can affect people from different age groups. The prime objective of epilepsy therapeutics is the targeted and sustained release of drugs at the site of action i.e. in the brain. In the present study, PLGA nanoparticles of gabapentin, coated with Polysorbate 80 were prepared with the aim of delivering the drug to the brain through the nasal route. The said nanoparticles were formulated by the method of double emulsion and solvent evaporation. Thereafter, the prepared nanoparticles were characterized for particle size, Zeta potential, and Surface morphology of the nanoparticles was evaluated by SEM &TEM In vitro release in PBS (pH 7.4) and SNF (pH 5.5). In addition, FTIR and DSC techniques were used to confirm the P80 coating around the nanoparticle's surface. In vitro, cell assays like Cytotoxicity studies, and quantitative and qualitative cell uptake studies were studied on Neuro-2a cells. The nasal mucosa of the goat was used to perform histopathological studies to evaluate the toxicity of nanoparticles. A biodistribution study was performed on Swiss albino mice and the results showed that the concentration of the drug reaching the brain in the case of P80 modified nanoparticles was maximum as compared to Plain PLGA nanoparticle, and aqueous solution of the drug. Pharmacodynamic studies were performed to assess the delay in different phases of convulsion and the results showed that the modified nanoparticles of gabapentin were able to significantly delay the episodes of convulsion. Overall, results demonstrate that modified nanoparticles are potential drug carriers in the brain for the management of epilepsy.

Coloaded Surface–Modified PLGA Nanoparticles for Sustained Ocular Delivery of Levofloxacin and Flurbiprofen

Coloaded Surface–Modified PLGA Nanoparticles for Sustained Ocular Delivery of Levofloxacin and Flurbiprofen

Surface modified biodegradable nanoparticles of Gabapentin. An approach to increase cell uptake

Improving delivery to the regions of Central Nervous System has been a long-explored quest for scientists. Delivery through nanocarriers provide potential solution but it is also important to choose material which is biodegradable in nature. Further once administered inside body these nanocarriers get cleared from the system very fast leading to poor bioavailability. It is important to modify surfaces of nanoparticles with materials which can improve the residence time as well as cellular uptake of drugs at the site of action. In the present study poly (lactic-co-glycolic acid) (PLGA) was used as a biodegradable polymer wherein the surface of the nanoparticles was modified with a cationic polymer, chitosan. Chitosan has been widely used in drug delivery via nasal route as it imparts mucoadhesive property to the nanoparticle there by increasing its mean residence time. Gabapentin was encapsulated in PLGA nanoparticles as it belongs to BCS class III, with low solubility and low permeability thus make it a suitable choice for delivering via surface modified nanoparticles so as to increase bioavailability. Chitosan coated PLGA nanoparticle loaded with gabapentin were prepared by nanoprecipitation method. Surface modified nanoparticles were optimized and developed to obtain smaller particle size (180.7 nm), zetapotential (36.7 mV) and maximum entrapment efficiency (75.6%). Optimized chitosan coated PLGA nanoparticle was further evaluated for its surface morphology by FTIR & DSC. Spherical nature of the nanoparticles was evaluated by SEM & TEM. Biphasic release pattern was observed for surface modified nanoparticles with sustained release up to 72 h. Optimized formulation was evaluated for % cell viability in comparison with uncoated nanoparticles and drug solution alone via MTT assay on Neuro-2a cells. Nanoparticle localization in neuro-2a cells was assessed by Confocal Laser Microscopy when treated with Rhodamine123 labelled Chitosan coated PLGA nanoparticles. These findings suggest a significant enhanced uptake of surface modified PLGA nanoparticles was observed as compared to uncoated nanoparticles.

Chitosan Surface-Modified PLGA Nanoparticles Loaded with Cranberry Powder Extract as a Potential Oral Delivery Platform for Targeting Colon Cancer Cells

Nutraceutical cranberry powder extract (CBPE) has distinct polyphenols inhibiting colon cancer growth and proliferation. However, its oral therapeutic efficacy is hindered because of its low permeability. This study aims to formulate chitosan surface-modified PLGA nanoparticles (CS-PLGA NPs) for encapsulating CBPE and modulating its release rate, permeation, cell targeting, and, therefore, its cytotoxicity. A full 23 factorial design is employed to scrutinize the effect of lactide/glycolide ratio, PLGA weight, and stabilizer concentrations on entrapment efficiency percentage (EE%), particle size (PS), polydispersity index (PDI), and zeta potential (ZP). The optimum formula (F4) shows spherical particles with a relatively high EE% (72.30 ± 2.86%), an appropriate size of 370.10 ± 10.31 nm, PDI; 0.398 ± 0.001, and ZP; -5.40 ± 0.21 mV. Alongside the ATR-FTIR outcomes, the chitosan surface-modified formula (CS-F4) demonstrates a significant increase in particle size (417.67 ± 6.77 nm) and a shift from negative to positive zeta potential (+21.63 ± 2.46 mV), confirming the efficiency of surface modification with chitosan. The intestinal permeability of F4 and CS-F4 is significantly increased by 2.19- and 3.10-fold, respectively, compared to the CBPE solution, with the permeability coefficient (Papp) being 2.05 × 10-4 cm/min and 2.91 × 10-4 cm/min, for F4 and CS-F4, respectively, compared to the CBPE solution, 9.36 × 10-5 cm/min. Moreover, CS-F4 evidences significant caspase-3 protein level expression stimulation and significant inhibition of vascular endothelial growth factor (VEGF) and signal transducer and activator of transcription-3 (STAT-3) protein expression levels, confirming the superiority of CS-F4 for targeting HT-29 cells. Briefly, CS-PLGA NPs could be regarded as a prosperous delivery system of CBPE with enhanced permeation, cell targeting, and antitumor efficacy.

Surface functionalization of PLGA nanoparticles for potential oral vaccine delivery targeting intestinal immune cells

This study aimed to develop surface modified PLGA nanocarriers protecting a protein-based antigen in the stomach to enable potential release of the antigen at target intestinal sites. PLGA nanoparticles (NPs) were prepared by double emulsion and solvent evaporation techniques while surface functionalization was performed using polyethylene glycol (PEG), sodium alginate (ALG) and Eudragit L100 (EUD) with ovalbumin (OVA) as a model protein antigen. Nanoparticles were characterized by dynamic light scattering (DLS), scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), gel permeation chromatography (GPC), and stability in simulated gastric fluid (SGF)/simulated intestinal fluid (SIF). Structural integrity of released OVA was analyzed by circular dichroism (CD) and sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), while cytotoxicity against Jurkat cells was determined using MTT assay. Surface functionalized PLGA NPs protected the protein in SGF and SIF better than the non-functionalized NPs. Average size of OVA encapsulated NPs was between 235 and 326 nm and were spherical. FTIR band change was observed after surface modification and the surface modified NPs showed sustained OVA release compared with the uncoated NPs. The secondary structure of OVA released after 96 h remained intact and MTT assay showed >80 % cell viability after 72 h while unmodified and surface modified NPs achieved 17 % and 48 % mucin binding respectively. In conclusion, surface modified PLGA NPs have been shown to be safe for potential oral protein-based vaccine delivery.

Immunological Assessment of Chitosan or Trimethyl Chitosan-Coated PLGA Nanospheres Containing Fusion Antigen as the Novel Vaccine Candidates Against Tuberculosis.

The crucial challenge in tuberculosis (TB) as a chronic infectious disease is to present a novel vaccine candidate that improves current vaccination and provides efficient protection in individuals. The present study aimed to evaluate the immune efficacy of multi-subunit vaccines containing chitosan (CHT)- or trimethyl chitosan (TMC)-coated PLGA nanospheres to stimulate cell-mediated and mucosal responses against Mycobacterium Tuberculosis (Mtb) in an animal model. The surface-modified PLGA nanoparticles (NPs) containing tri-fusion protein from three Mtb antigens were produced by the double emulsion technique. The subcutaneously or nasally administered PLGA vaccines in the absence or presence of BCG were assessed to compare the levels of mucosal IgA, IgG1, and IgG2a production as well as secretion of IFN-γ, IL-17, IL-4, and TGF-β cytokines. According to the release profile, the tri-fusion encapsulated in modified PLGA NPs demonstrated a biphasic release profile including initial burst release on the first day and sustained release within 18days. All designed PLGA vaccines induced a shift of Th1/Th2 balance toward Th1-dominant response. Although immunized mice through subcutaneous injection elicited higher cell-mediated responses relative to the nasal vaccination, the intranasally administered groups stimulated robust mucosal IgA immunity. The modified PLGA NPs using TMC cationic polymer were more efficient to elevate Th1 and mucosal responses in comparison with the CHT-coated PLGA nanospheres. Our findings highlighted that the tri-fusion loaded in TMC-PLGA NPs may represent an efficient prophylactic vaccine and can be considered as a novel candidate against TB.

Formulation of PPAR-gamma agonist as surface modified PLGA nanoparticles for non-invasive treatment of diabetic retinopathy: in vitro and in vivo evidences

Diabetic retinopathy is one of the worst complications of diabetes and it is treated by invasive method. We prepared a surface modified poly (D, L-lactide-co-glycolide) i.e. PLGA nanoparticles for delivery of pioglitazone-a peroxisome proliferator-activated receptor-gamma agonist to posterior segment of the eye by topical administration. The present study investigated two grades of PLGA viz. 75:25 and 50:50. Surface modification was performed using polysorbate 80. Nanoparticles were prepared by single emulsion solvent evaporation method and optimized by using 3-factor 3-level Box-Behnken statistical design. Mean particle size, PDI and entrapment efficiency for optimized batch of PLGA 75:25 was found to be 163.23 nm, 0.286 and 91%, whereas; for PLGA 50:50 it was 171.7 nm, 0.280 and 93% respectively. DSC confirms the molecular dispersion of drug in polymer. In vitro release study showed biphasic drug release pattern with 58.48 ± 1.38% and 74.17 ± 1.38% cumulative drug release by PLGA 75:25 and 50:50 nanoparticles at the end of 10h. The release profile of pioglitazone from nanoparticles appeared to fit best with Higuchi model. In vivo study on rat showed dose dependent reduction in vascular endothelial growth factor concentration in vitreous fluid. The study reveals significance of peroxisome proliferator-activated receptor-gamma in management of diabetic retinopathy.

Chitosan surface modified PLGA nanoparticles loaded with brigatinib for the treatment of non-small cell lung cancer

Abstract In the current study, surface-modified poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) of brigatinib (BRB) were prepared by studying the variables PLGA (polymer), PVA (stabilizer) and chitosan (coater) against experimentally obtained responses. The optimized NPs (F2) were evaluated in vitro for differential scanning calorimetry (DSC), Fourier transform infrared (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM), particle size, polydispersity index (PDI) and drug entrapment (EE), in vitro release, hematocompatibility and in vitro anticancer studies. The optimized NPs’ (F2) composition, PLGA (75 mg), PVA (0.55% w/v), chitosan (0.75% w/v) and 30 mg of BRB was found to be optimum with particle size (406.3 ± 5.1 nm), PDI (0.277), ζ potential (30.4 ± 3.3 mV) and %EE (82.32%). The in vitro release profile showed a sustained release pattern of the F2 nanoparticles of BRB. The 3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay revealed a significant anticancer activity for F2 NPs against A549 cell lines in comparison to free BRB. The result obtained in this work indicated the immense potential of nanoparticles to effectively deliver the BRB to the cancer site for the treatment of non-small cell lung cancer.

Cationic polymer modified PLGA nanoparticles encapsulating Alhagi honey polysaccharides as a vaccine delivery system for ovalbumin to improve immune responses.

Background: Poly (lactic-co-glycolic acid) (PLGA) nanoparticles and surface modified PLGA nanoparticles have been widely studied as antigens or drugs carriers due to their controlled release characteristics and biocompatibility. However, most PLGA nanoparticles have lower antigens loading efficiency and adjuvanticity.Purpose: The aim of this study was to improve the antigen loading efficiency and adjuvant activity of PLGA nanoparticles.Materials and methods: Surface cationic polymer modification can improve the antigens loading efficiency of PLGA nanoparticles by surface adsorption. Therefore, in this study, chitosan modified PLGA nanoparticles (CS-AHPP/OVA), polyethyleneimine modified PLGA nanoparticles (PEI-AHPP/OVA), and ε-Poly-L-lysine modified PLGA nanoparticles (εPL-AHPP/OVA) were prepared as antigen delivery carriers to investigate the characterization and stability of these nanoparticles. These nanoparticles were evaluated for their efficacies as adjuvants pre- and post-modification.Results: The AHP and OVA-loaded PLGA nanoparticles (AHPP/OVA) were positively charged after surface cationic polymers modification, and their structural integrity was maintained. Their antigen loading capacity and stability of nanoparticles were improved by the surface cationic polymers modification. Increased positive surface charge resulted in greater OVA adsorption capacity. Among AHPP/OVA and the three surface cationic polymers synthesized from modified PLGA nanoparticles, PEI-AHPP/OVA showed the highest antigen loading efficiency and good stability. AHPP/OVA, CS-AHPP/OVA PEI-AHPP/OVA, and εPL-AHPP/OVA formulations significantly enhanced lymphocyte proliferation and improved the ratio of CD4+/CD8+ T cells. In addition, AHPP/OVA, PEI-AHPP/OVA and εPL-AHPP/OVA formulations induced secretion of cytokines (TNF-α, IFN-γ, IL-4, and IL-6), antibodies (IgG) and antibody subtypes (IgG1 and IgG2a) in immunized mice. These results demonstrate that these formulations generated a strong Th1-biased immune response. Among them, PEI-AHPP/OVA induced the strongest Th1-biased immune response.Conclusion: In conclusion, PEI-AHPP/OVA nanoparticles may be a potential antigen delivery system for the induction of strong immune responses.

Surface-modified PLGA nanoparticles with PEG/LA-chitosan for targeted delivery of arsenic trioxide for liver cancer treatment: Inhibition effects enhanced and side effects reduced

Arsenic trioxide (As2O3), an effective drug for leukemia, is limited to be used for solid tumor treatment due to its high side effects. In this study, polyethylene glycol (PEG) and lactobionic acid (LA) modified chitosan (PLC) was synthesized and was used to coat poly(lactide-co-glycolide) (PLGA) nanoparticles for encapsulation and targeted release of As2O3 in liver cancer treatment. The As2O3-loaded PLGA/PLC nanoparticles (As2O3-PLGA/PLC NPs) were fabricated through double emulsion-solvent evaporation method and were optimized by orthogonal tests. As2O3-PLGA/PLC NPs presented suitable physical stability, positive charge, high encapsulation efficiency and drug loading, and good biocompatibility. As expected, the NPs can quickly release enough dose of As2O3 in a short time and then sustain the drug concentration. The As2O3-PLGA/PLC NPs showed effective inhibition of SMMC-7721 cells while having lower cytotoxicity against normal human liver cells (LO2 cells). Furthermore, In vivo study showed that the NPs did not present toxic effects on kidney and liver, but showed relatively high growth inhibition effect on liver tumor. Therefore, this PLGA/PLC NPs could be an effective and safe drug delivery system for liver cancer chemotherapy.

Efficacy of Surface-Modified PLGA Nanoparticles as a Function of Cervical Cancer Type.

Hypovascularization of cervical tumors, coupled with intrinsic and acquired drug resistance, has contributed to marginal therapeutic outcomes by hindering chemotherapeutic transport and efficacy. Recently, the heterogeneous penetration and distribution of cell penetrating peptide (CPP, here MPG) and polyethylene glycol (PEG) modified poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) were evaluated as a function of tumor type and morphology in cervical cancer spheroids modeling hypovascularized tumor nodules. Building upon this work, this study investigates the efficacy imparted by surface-modified Doxorubicin-loaded NPs transported into hypovascularized tissue. NP efficacy was measured in HeLa, CaSki, and SiHa cells. NP internalization and association, and associated cell viability, were determined in monolayer and spheroid models. MPG and PEG-NP co-treatment was most efficacious in HeLa cells, while PEG NPs were most efficacious in CaSki cells. NP surface-modifications were unable to improve efficacy, relative to unmodified NPs, in SiHa cells. The results highlight the dependence of efficacy on tumor type and the associated microenvironment. The results further relate previous NP transport studies to efficacy, as a function of surface-modification and cell type. Longer-term, this information may help guide the design of NP-mediated strategies to maximize efficacy based on patient-specific cervical tumor origin and characteristics.

Formulation of functionalized PLGA nanoparticles with folic acid-conjugated chitosan for carboplatin encapsulation

Poly(d,l-lactic-co-glycolic acid), or PLGA, is the most frequently used biodegradable and biocompatible polymer in preparation of nanoparticles for biomedical applications. In this work nanoparticles composed of PLGA were prepared to produce nanocarriers for a platinum-based antitumoral drug: carboplatin. The carboplatin-loaded PLGA nanoparticles were obtained by nanoprecipitation method, using TPGS (D-α-tocopheryl polyethylene glycol succinate) as stabilizer and acetone as organic phase. In order to improve the delivery of carboplatin to cancer cells, folic acid-conjugated chitosan-coated (FA-CS) PLGA nanoparticles were also prepared, using 22 factorial design with center point for unmodified and surface modified nanoparticles. For PLGA nanoparticles, the results showed that mean particle size is dependent of time, amplitude of sonication, volume and concentration of TPGS aqueous solution (according to a linear model), while PDI and zeta potential are constants. The optimized formulation (121.0 nm, PDI = 0.120 and −34.0 mV) was stable over a period of 60 days when stored at 10 °C, with entrapment efficiency (EE) = 5%, drug loading = 0.37% and nanoparticle yield = 77%. Also, it was possible to improve these parameters (EE = 39.5%, drug loading = 2.6% and yield = 91%) by reduction of dialysis (24–2 h) and acetone evaporation (24–1 h) time. For surface modified PLGA nanoparticles, mean particle size and PDI are dependent of stirring time and concentration of FA-CS solution (according to a quadratic model), while zeta potential is also dependent of these factors but according to a linear model. The optimal formulation showed particles with size of 178.0 nm, PDI = 0.20, zeta potential = 46.0 mV, EE = 35.5%, drug loading = 1.8% and nanoparticle yield = 92%. Encapsulation of carboplatin was confirmed by UV–Vis spectroscopy using a derivatization technique with orto-phenylenediamine. In conclusion, the results obtained in this work demonstrated that formulation variables can be explored to obtain the optimal preparation conditions of PLGA nanoparticles.

Intranasal delivery of Huperzine A to the brain using lactoferrin-conjugated N-trimethylated chitosan surface-modified PLGA nanoparticles for treatment of Alzheimer's disease.

BackgroundSafe and effective delivery of therapeutic drugs to the brain is important for successful therapy of Alzheimer’s disease (AD).PurposeTo develop Huperzine A (HupA)-loaded, mucoadhesive and targeted polylactide-co-glycoside (PLGA) nanoparticles (NPs) with surface modification by lactoferrin (Lf)-conjugated N-trimethylated chitosan (TMC) (HupA Lf-TMC NPs) for efficient intranasal delivery of HupA to the brain for AD treatment.MethodsHupA Lf-TMC NPs were prepared using the emulsion–solvent evaporation method and optimized using the Box–Behnken design. The particle size, zeta potential, drug entrapment efficiency, adhesion and in vitro release behavior were investigated. The cellular uptake was investigated by fluorescence microscopy and flow cytometry. MTT assay was used to evaluate the cytotoxicity of the NPs. In vivo imaging system was used to investigate brain targeting effect of NPs after intranasal administration. The biodistribution of Hup-A NPs after intranasal administration was determined by liquid chromatography–tandem mass spectrometry.ResultsOptimized HupA Lf-TMC NPs had a particle size of 153.2±13.7 nm, polydispersity index of 0.229±0.078, zeta potential of +35.6±5.2 mV, drug entrapment efficiency of 73.8%±5.7%, and sustained release in vitro over a 48 h period. Adsorption of mucin onto Lf-TMC NPs was 86.9%±1.8%, which was significantly higher than that onto PLGA NPs (32.1%±2.5%). HupA Lf-TMC NPs showed lower toxicity in the 16HBE cell line compared with HupA solution. Qualitative and quantitative cellular uptake experiments indicated that accumulation of Lf-TMC NPs was higher than nontargeted analogs in 16HBE and SH-SY5Y cells. In vivo imaging results showed that Lf-TMC NPs exhibited a higher fluorescence intensity in the brain and a longer residence time than nontargeted NPs. After intranasal administration, Lf-TMC NPs facilitated the distribution of HupA in the brain, and the values of the drug targeting index in the mouse olfactory bulb, cerebrum (with hippocampus removal), cerebellum, and hippocampus were about 2.0, 1.6, 1.9, and 1.9, respectively.ConclusionLf-TMC NPs have good sustained-release effect, adhesion and targeting ability, and have a broad application prospect as a nasal drug delivery carrier.

Surface-modified PLGA nanoparticles with chitosan for oral delivery of tolbutamide

The main purpose of present study was to develop novel chitosan-modified polylactic-co-glycolicacid nanoparticles (CS@PLGA NPs) for improving the bio-availability of tolbutamide (TOL). The TOL-loaded CS@PLGA NPs (TOL-CS@PLGA NPs) were fabricated with the solvent evaporation method. The cargo-free CS@PLGA NPs showed a diameter of 228.3±2.5nm monitored with a laser light particlesizer, and the transmission electron microscope (TEM) photographs revealed their “core-shell” structures. The Zeta potential of the original PLGA NPs and the cargo-free CS@PLGA NPs was measured to be −20.2±3.21mV and 24.2±1.1mV, respectively. The changes in Zeta potential indicated the CS chains were coated on the surfaces of the original PLGA NPs. The thermal gravity analysis (TGA) curves suggested that the CS chains improved the thermostability of the original PLGA NPs. The results of cells viability indicated the cargo-free CS@PLGA NPs were nontoxicity. The in vitro release profiles suggested that TOL-CS@PLGA NPs could release TOL in pH 7.4 phosphate buffer solution (PBS) at a sustained manner. Streptozotocin (STZ) was employed to build the diabetic rat models. The physiological changes in the islet β cells confirmed the obtaining of diabetic rats. After treatment by gavage, the TOL-CS@PLGA NPs showed an excellent hypoglycemic effect. Therefore, the TOL-CS@PLGA NPs had a potential application in oral delivery of TOL.

Feasibility of drug delivery to the eye's posterior segment by topical instillation of PLGA nanoparticles

We investigated the delivery of drugs to the posterior segment of the eye by non-invasive topical instillation using submicron-sized poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles (NPs). Surface-modified PLGA NPs were developed to improve the drug delivery efficiency to the retina and were administered as topical eye drops to mice. Chitosan (CS) and glycol chitosan (GCS), which are mucoadhesive polymers, and polysorbate 80 (P80) were used as surface modifiers, and have been reported to increase the association of NPs with cells. Coumarin-6 was used as a model drug and fluorescent marker, and after ocular administration of PLGA NP eye drops, the fluorescence intensity of coumarin-6 was observed in the retina. The fluorescence image analysis indicated that there are several possible routes to the retina and fates of PLGA NPs in ocular tissue, and that these pathways involved the corneal, non-corneal, or uveal routes. Delivery to the mouse retina segments after topical administration was increased by surface modification with CS, GCS, or P80. Surface-modified PLGA NPs are a promising method for retinal drug delivery via topical instillation.

Toxicity, pharmacokinetics, and in vivo efficacy of biotinylated chitosan surface-modified PLGA nanoparticles for tumor therapy

Based on our previous work on the PLGA nanoparticles modified with biotinylated chitosan (Bio-CS-PLGA NPs), we further studied the stability, toxicity, pharmacokinetics, and in vivo efficacy. The safety of NPs was studied through single-dose toxicity test in mice, and the result showed that NPs were well tolerated at the dose of 300 mg/kg. Compared with the free EPB group, the NPs group exhibited higher plasma drug concentration, longer half-life time. EPB-loaded NPs significantly inhibited the tumor growth compared to free EPB. All results suggested that Bio-CS-PLGA NPs were stable, safe, and showed a promising potential on targeted drug delivery.

Revisiting bone targeting potential of novel hydroxyapatite based surface modified PLGA nanoparticles of risedronate: Pharmacokinetic and biochemical assessment

Hydroxyapatite based biodegradable mPEG-PLGA nanoparticles of risedronate (mPEG-PLGA-RIS-HA) were prepared by water miscible dialysis method for synergistic treatment of osteoporosis. The bone targeting potential of prepared nanoparticles was evaluated by performing the cell viability study and protein estimation in pre-osteoblast cell line (MC3T3E1). Biochemical and in-vivo pharmacokinetic studies on osteoporotic rat model treated with different formulations were performed. Under the biochemical study ALP, TRAP, HxP and Calcium levels were determined. Osteoporotic model treated with prepared nanoparticles indicated significant effect on bone. Pharmacokinetic studies revealed 6-fold and 4-fold increase in the relative bioavailability after intravenous and oral administration of nanoparticles respectively as compared to marketed formulation confirming better effective drug transport. Biochemical investigations also showed a significant change in biomarker level which ultimately lead to bone formation/resorption. A stability analysis has also been carried out according to ICH guidelines (Q1AR2) and shelf life was found to be 1year and 4 months for the prepared formulation. Thus the results of present studies indicated that mPEG-PLGA-RIS-HA NPs has a great potential for sustained delivery of RIS for the treatment and prevention of osteoporosis and to minimize the adverse effects of RIS typically induced by its oral administration.

Carboplatin loaded Surface modified PLGA nanoparticles: Optimization, characterization, and in vivo brain targeting studies

The carboplatin (CP) loaded poly-lactide-co-glycolide (PLGA) nanoparticles (NPs) were formulated by modified solvent evaporation method. Its surface modification is done by 1% polysorbate80 (P80) to improve their entry into the brain after intraperitoneal administration (i.p) via receptor-mediated pathways. A formulation with maximum entrapment efficiency and minimal particle size was optimized by central composite design (CCD) based on mean particle size, and entrapment efficiencies as responses. The optimized formulation was characterized by mean particle size, entrapment efficiency, zeta potential, Fourier transform infrared (FTIR), X-ray diffraction (XRD), differential scanning calorimetry (DSC) and scanning electron microscopy (SEM) analysis. The surface modified NPs were analysed for mean particle, zeta potential, FTIR, and in vitro release studies. The spherical particles with mean particle size 161.9nm, 162.4nm and zeta potential value of −26.5, −23.9 were obtained for unmodified and surface modified NPs respectively. The in vitro release experiments of the surface modified PLGA NPs exhibited sustained release for more than 48h, which was in accordance with Higuchi’s equation with Fickian diffusion-based release mechanism. The in vivo bio distribution of P80 coated CP loaded PLGA NPs was compared with CP solution, and CP loaded NPs, in adult wistar rats. In the brain, compared with CP solution, both types of NPs especially NPs coated with P80 increased the concentration of carboplatin by 3.27 fold. All these results suggest that the developed formulation may improve the targeted therapy for malignant brain tumors in future.

Transferrin surface-modified PLGA nanoparticles-mediated delivery of a proteasome inhibitor to human pancreatic cancer cells.

The aim of this study was to develop a drug delivery system based on poly(lactic-co-glycolic acid) (PLGA) nanoparticles for an efficient and targeted action of the proteasome inhibitor bortezomib against pancreatic cancer cells. The PLGA nanoparticles were formulated with a poloxamer, and further surface-modified with transferrin for tumor targeting. The nanoparticles were characterized as polymer carriers of bortezomib, and the cellular uptake and growth inhibitory effects were evaluated in pancreatic cells. Cellular internalization of nanoparticles was observed in normal and cancer cells, but with higher uptake by cancer cells. The sustained release of the loaded bortezomib from PLGA nanoparticles showed cytotoxic effects against pancreatic normal and cancer cells. Noteworthy differential cytotoxicity was attained by transferrin surface-modified PLGA nanoparticles since significant cell growth inhibition by delivered bortezomib was only observed in cancer cells. These findings demonstrate that the ligand transferrin enhanced the targeted delivery of bortezomib-loaded PLGA nanoparticles to pancreatic cancer cells. These in vitro results highlight the transferrin surface-modified PLGA nanoparticles as a promising system for targeted delivery of anticancer drugs.

Surface modified PLGA nanoparticles for brain targeting of Bacoside-A

The present paper focuses on the development and in vitro/in vivo characterization of nanoparticles composed of poly-(D,L)-Lactide-co-Glycolide (PLGA) loading Bacoside-A, as a new approach for the brain delivery of the neuroprotective drug for the treatment of neurodegenerative disorders (e.g. Alzheimer Disease). Bacoside-A-loaded PLGA nanoparticles were prepared via o/w emulsion solvent evaporation technique. Surface of the nanoparticles were modified by coating with polysorbate 80 to facilitate the crossing of the blood brain barrier (BBB), and the processing parameters (i.e. sonication time, the concentration of polymer (PLGA) and surfactant (polysorbate 80), and drug-polymer ratio) were optimized with the aim to achieve a high production yield. Brain targeting potential of the nanoparticles was evaluated by in vivo studies using Wistar albino rats. The nanoparticles produced by optimal formulation were within the nanosized range (70–200nm) with relatively low polydispersity index (0.391±1.2). The encapsulation efficiency of Bacoside-A in PLGA nanoparticles was 57.11±7.11%, with a drug loading capacity of 20.5±1.98%. SEM images showed the spherical shape of the PLGA nanoparticles, whereas their low crystallinity was demonstrated by X-ray studies, which also confirmed no chemical interactions between the drug and polymer molecules. The in vitro release of Bacoside-A from the PLGA nanoparticles followed a sustained release pattern with a maximum release of up to 83.04±2.55% in 48h. When compared to pure drug solution (2.56±1.23μg/g tissue), in vivo study demonstrated higher brain concentration of Bacoside-A (23.94±1.74μg/g tissue) suggesting a significant role of surface coated nanoparticles on brain targeting. The results indicate the potential of surface modified PLGA nanoparticles for the delivery of Bacoside-A to the brain.