Effect of the Freezing Step in the Stability and Bioactivity of Protein-Loaded PLGA Nanoparticles Upon Lyophilization

Purpose

The freezing step in lyophilization is the most determinant for the quality of biopharmaceutics. Using insulin as model of therapeutic protein, our aim was to evaluate the freezing effect in the stability and bioactivity of insulin-loaded PLGA nanoparticles. The performance of trehalose, sucrose and sorbitol as cryoprotectants was evaluated.

Methods

Cryoprotectants were co-encapsulated with insulin into PLGA nanoparticles and lyophilized using an optimized cycle with freezing at ?80°C, in liquid nitrogen, or ramped cooling at ?40°C. Upon lyophilization, the stability of protein structure and in vivo bioactivity were assessed.

Results

Insulin was co-encapsulated with cryoprotectants resulting in particles of 243–394 nm, zeta potential of ?32 to ?35 mV, and an association efficiency above 90%. The cryoprotectants were crucial to mitigate the freezing stresses and better stabilize the protein. The insulin structure maintenance was evident and close to 90%. Trehalose co-encapsulated insulin-loaded PLGA nanoparticles demonstrated enhanced hypoglycemic effect, comparatively to nanoparticles without cryoprotectant and added with trehalose, due to a superior insulin stabilization and bioactivity.

Conclusions

The freezing process may be detrimental to the structure of protein loaded into nanoparticles, with negative consequences to bioactivity. The co-encapsulation of cryoprotectants mitigated the freezing stresses with benefits to protein bioactivity.

     

Effect of Nanoparticle Surface on the HPLC Elution Profile of Liposomal Nanoparticles

Purpose

Nanoparticles have been used in diverse areas, and even broader applications are expected in the future. Since surface modification can influence the configuration and toxicity of nanoparticles, a rapid screening method is important to ensure nanoparticle quality.

Methods

We examined the effect of the nanoparticle surface morphology on the HPLC elution profile using two types of 100-nm liposomal nanoparticles (AmBisome^? and DOXIL^?).

Results

These 100-nm-sized nanoparticles eluted before the holdup time (about 4 min), even when a column packed with particles with a relatively large pore size (30 nm) was used. The elution time of the nanoparticles increased with pegylation of the nanoparticles and protein adsorption to the nanoparticles; however, the nanoparticles still eluted before the holdup time.

Conclusions

The results of this study indicate that HPLC is a suitable tool for rapid evaluation of the surface of liposomal nanoparticles.

     

Supramolecular Chitosan Micro-Platelets Synergistically Enhance Anti-<Emphasis Type="BoldItalic">Candida albicans</Emphasis> Activity of Amphotericin B Using an Immunocompetent Murine Model

Purpose

The aim of this work is to design new chitosan conjugates able to self-organize in aqueous solution in the form of micrometer-size platelets. When mixed with amphotericin B deoxycholate (AmB-DOC), micro-platelets act as a drug booster allowing further improvement in AmB-DOC anti-Candida albicans activity.

Methods

Micro-platelets were obtained by mixing oleoyl chitosan and α-cyclodextrin in water. The formulation is specifically-engineered for mucosal application by dispersing chitosan micro-platelets into thermosensitive pluronic^® F127 20 wt% hydrogel.

Results

The formulation completely cured C. albicans vaginal infection in mice and had a superior activity in comparison with AmB-DOC without addition of chitosan micro-platelets. In vitro studies showed that the platelets significantly enhance AmB-DOC antifungal activity since the IC₅₀ and the MIC₉₀ decrease 4.5 and 4.8-times. Calculation of fractional inhibitory concentration index (FICI?=?0.198) showed that chitosan micro-platelets act in a synergistic way with AmB-DOC against C. albicans. No synergy is found between spherical nanoparticles composed poly(isobutylcyanoacrylate)/chitosan and AmB-DOC.

Conclusion

These results demonstrate for the first time the ability of flattened chitosan micro-platelets to have synergistic activity with AmB-DOC against C. albicans candidiasis and highlight the importance of rheological and mucoadhesive behaviors of hydrogels in the efficacy of the treatment.

     

Budesonide Loaded PLGA Nanoparticles for Targeting the Inflamed Intestinal Mucosa—Pharmaceutical Characterization and Fluorescence Imaging

Purpose

The purpose of this study was to evaluate the specifically targeted efficiency of budesonide loaded PLGA nanoparticles for the treatment of inflammatory bowel disease (IBD).

Methods

The nanoparticles were prepared by an oil/water (O/W) emulsion evaporation technique. The nanoparticles were characterized for their size, shape and in vitro drug release profile. Solid state characterization was carried out by differential scanning calorimetry (DSC) and X-ray Power diffraction (XPRD). In order to evaluate the targeted efficiency of nanoparticles, a particle localization study in the healthy and in the inflamed colon was determined in vivo. These data were complemented by cryo-sections.

Results

Nanoparticles were 200?±?05 nm in size with a smooth and spherical shape. The encapsulation efficiency was around 85?±?3.5%, which was find-out by both, direct and indirect methods. Release of budesonide from the nanoparticles showed a biphasic release profile with an initial burst followed by sustained release. XPRD data revealed that the drug in the polymer matrix existed in crystalline state. Nanoparticles accumulation in inflamed tissues was evaluated by in-vivo imaging system and it was found that particles are accumulated in abundance at the site of inflammation when compared to the healthy group.

Conclusion

The study demonstrates that the budesonide loaded PLGA nanoparticles are an efficient delivery system for targeted drug delivery to the inflamed intestinal mucosa.

     

Progesterone PLGA/mPEG-PLGA Hybrid Nanoparticle Sustained-Release System by Intramuscular Injection

Purpose

To prepare sustained-release PLGA/mPEG-PLGA hybrid nanoparticles of progesterone (PRG), and evaluate the descending required administration dosage in vivo.

Methods

PRG hybrid nanoparticles (PRG H-NPs) based on PLGA/mPEG-PLGA were compared with PRG nanoparticles (PRG-NPs) of pure PLGA as the matrix and PRG-oil solutions. Nanoparticles (NPs) were formed by the method of nanoemulsion, and the pharmacokinetics of the sustained-release PRG H-NPs in male Sprague dawley (SD) rats were investigated. The rats were randomly divided into four groups, each group received: single dose of PRG H-NPs (14.58 mg/kg, i.m.) and PRG-NPs (14.58 mg/kg, i.m.), repeated dosing for 7 days of PRG-oil (2.08 mg/kg, i.m.) solution (Oil-L) and a higher dosage of PRG-oil (6.24 mg/kg, i.m.) solution (Oil-H), respectively.

Results

In the pharmacokinetic test, the PRG H-NPs exhibited a comparatively good sustained-release effect against the PRG-NPs without mPEG-PLGA and PRG-oil solution. The pharmacokinetic parameters of the PRG H-NPs, PRG-NPs, Oil-L and Oil-H were AUC_0–t(ng·h·mL^?1) 8762.1, 1546.1, 1914.5, and 12,138.9, t_1/2 (h)52.7, 44.1, 8.4 and 44.6 respectively.

Conclusions

Owing to the modification of PEG, PRG H-NPs can act as safe delivery platforms for sustained-release of drugs with a lower dosage required.

     

Structural Stability of Recombinant Human Growth Hormone (r-hGH) as a Function of Polymer Surface Properties

Purpose

Despite the fact that r-hGH was first approved for use by FDA in 1995 and the conventional dosage form in the market has a limitation of daily subcutaneous injections, there remains a lack of sustained delivery system in the market. Nutropin depot, a long-acting dosage form of r-hGH was approved for marketing by FDA in 1999, however, it was discontinued in 2004. Since then, unabating efforts have been made to develop biodegradable polymer based formulations for r-hGH delivery. However, grey area is the comprehension of structural stability of r-hGH at an interface with the polymer and it is of utmost important to attain safe and efficacious sustained delivery system. The purpose of this study was to evaluate the changes in structure of r-hGH upon adsorption at biodegradable PLGA nanoparticles of different hydrophobicity as a function of pH.

Methods

DLS, fluorescence spectroscopy, and CD were collectively employed to evaluate structural changes in r-hGH.

Results

The studies revealed that r-hGH is most stable with low to high hydrophobicity PLGA grades under pH 7.2 followed by 5.3.

Conclusion

Overall, the nature and magnitude of structural changes observed has a strong dependence on the pH and differences and degree of hydrophobicity of PLGA.

     

Activation of Antigen-Specific CD8<Superscript>+</Superscript> T Cells by Poly-DL-Lactide/Glycolide (PLGA) Nanoparticle-Primed Gr-1<Superscript>high</Superscript> Cells

Purpose

The aim of this study was to investigate the induction of antigen-specific T cell activation and cell cycle modulation by a poly-DL-lactide/glycolide (PLGA) nanoparticle (NP)-primed CD11b⁺Gr-1^high subset isolated from mouse bone marrow.

Methods

PLGA NPs containing the ovalbumin (OVA) antigen were prepared using the double emulsion and solvent evaporation method, and protein release rate and cell viability were determined. The Lin2^¯CD11b⁺Gr-1^highLy6c^low (Gr-1^high) subset was sorted from the bone marrow of C57BL/6 J mice by fluorescence-activated cell sorting (FACS) and co-cultured with OT-I CD8⁺ splenic T cells. Proliferation of OT-I CD8⁺ T cells was monitored, and cell cycles were determined by 5-bromo-2′-deoxyuridine (BrdU) labeling.

Results

Treatment of Gr-1^high cells with PLGA/OVA NPs upregulated expression of the SIINFEKL-H2K^b complex in the context of MHC I. Co-cultures of OT-I CD8⁺ T cells with the PLGA/OVA NP-primed Gr-1^high cells induced the proliferation of T cells in vitro and modulated cell division and morphology. Treatment of Gr-1^high cells with PLGA/OVA NPs also induced cell apoptosis and necrosis.

Conclusion

This study demonstrated the function of PLGA/OVA NPs in the activation of OT-I CD8⁺ T cells and the capability of cross-presentation via the Gr-1^high polymorphonuclear subset from mouse bone marrow.

     

Preparation and Evaluation of PLGA-Coated Capsaicin Magnetic Nanoparticles

Purpose

Drugs used in the treatment of diseases can cause several unwanted systemic side effects. A site-specific drug delivery system can eliminate such consequences by delivering drugs to certain target areas of the body where therapeutic effects are required. Here we present the preparation and evaluation of magnetic nanoparticles of capsaicin, the active ingredient in chili peppers, coated with poly-L-lactide co-glycolide (PLGA), a FDA-approved biodegradable bioavailable polymer.

Methods

PCMN were prepared by solvent-evaporation/coprecipitation technique and their physicochemical and pharmacological characteristics evaluated in vitro. Further, effective pain/inflammation therapeutics of PCMN in a mouse model of inflammation was also studied. We also prepared and evaluated the subcellular localization of PLGA coated fluorescence magnetic nanoparticle (PFMN) in vitro in HEK293 cells.

Results

Transmission electron microscopic images of PCMN showed that the size of the nanoparticles were of the order of 10–20 nm. PCMN showed approximately 9.29% drug loading and 89.15% encapsulation efficiencies. In vitro dissolution studies showed an increased solubility of capsaicin due to the nano-size of the PCMN, while PLGA coating allowed sustained release of capsaicin in vitro. The PCMN also reduced paw edema after injection in mice, and confocal microscopy revealed the successful intracellular localization of PLGA-coated fluorescein magnetic nanoparticles in HEK293 cells.

Conclusion

The PCMN provided a sustained release of capsaicin in vitro and inhibited carrageenan-induced inflammatory pain in mouse model in vivo. These data suggest that PLGA coating of capsaicin magnetic nanoparticles have the potential to be amenable for a sustained release of capsaicin to relieve pain.

     

Functionalization of PLGA Nanoparticles with 1,3-β-glucan Enhances the Intracellular Pharmacokinetics of Rifampicin in Macrophages

Purpose

Mycobacterium tuberculosis which causes tuberculosis, is primarily resident within macrophages. 1,3-β-glucan has been proposed as a ligand to target drug loaded nanoparticles (NPs) to macrophages. In this study we characterized the intracellular pharmacokinetics of the anti-tubercular drug rifampicin delivered by 1,3-β-glucan functionalized PLGA NPs (Glu-PLGA). We hypothesized that Glu-PLGA NPs would be taken up at a faster rate than PLGA NPs, and consequently deliver higher amounts of rifampicin into the macrophages.

Methods

Carbodiimide chemistry was employed to conjugate 1,3-β-glucan and rhodamine to PLGA. Rifampicin loaded PLGA and Glu-PLGA NPs as well as rhodamine functionalized PLGA and Glu-PLGA NPs were synthesized using an emulsion solvent evaporation technique. Intracellular pharmacokinetics of rifampicin and NPs were evaluated in THP-1 derived macrophages. A pharmacokinetic model was developed to describe uptake, and modelling was performed using ADAPT 5 software.

Results

The NPs increased the rate of uptake of rifampicin by a factor of 17 and 62 in case of PLGA and Glu-PLGA, respectively. Expulsion of NPs from the macrophages was also observed, which was 3 fold greater for Glu-PLGA NPs than for PLGA NPs. However, the ratio of uptake to expulsion was similar for both NPs. After 24 h, the amount of rifampicin delivered by the PLGA and Glu-PLGA NPs was similar. The NPs resulted in at least a 10-fold increase in the uptake of rifampicin.

Conclusions

Functionalization of PLGA NPs with 1,3-β-glucan resulted in faster uptake of rifampicin into macrophages. These NPs may be useful to achieve rapid intracellular eradication of Mycobacterium tuberculosis.

     

Fabrication of 3-O-sn-Phosphatidyl-L-serine Anchored PLGA Nanoparticle Bearing Amphotericin B for Macrophage Targeting

Purpose

To fabricate, characterize and evaluate 3-O-sn-Phosphatidyl-L-serine (PhoS) anchored PLGA nanoparticles for macrophage targeted therapeutic intervention of VL.

Materials and Methods

PLGA-AmpB NPs were prepared by well-established nanoprecipitation method and decorated with Phos by thin film hydration method. Physico-chemical characterization of the formulation was done by Zetasizer nano ZS and atomic force microscopy.

Results

The optimized formulation (particle size, 157.3?±?4.64 nm; zeta potential, ? 42.51?±?2.11 mV; encapsulation efficiency, ～98%) showed initial rapid release up to 8 h followed by sustained release until 72 h. PhoS generated ‘eat-me’ signal driven augmented macrophage uptake, significant increase in in-vitro (with ～82% parasite inhibition) and in-vivo antileishmanial activity with preferential accumulation in macrophage rich organs liver and spleen were found. Excellent hemo-compatibility justified safety profile of developed formulation in comparison to commercial formulations.

Conclusion

The developed PhoS-PLGA-AmpB NPs have improved efficacy, and necessary stability which promisingly put itself as a better alternative to available commercial formulations for optimized treatment of VL.

     

Lyophilized Nanosuspensions for Oral Bioavailability Improvement of Insoluble Drugs: Preparation,Characterization, and Pharmacokinetic Studies

Purpose

We describe here a novel lyophilized nanosuspension technology in order to improve the dissolution rate and oral bioavailability of the insoluble drug P2X7 receptor antagonist (PRA), which is an effective antagonist to P2X7 receptor for non-steroidal anti-inflammatory.

Methods

PRA-lyophilized nanosuspension (PRA-LNS) was fabricated by anti-solvent precipitation in combination with high pressure homogenization, and then lyophilized for prolonged storage. After preparations, various characterization experiments were performed including particle size, zeta potential, surface morphology, X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), in vitro dissolution study, and in vivo pharmacokinetic study.

Results

The re-dissolved particle size of PRA-LNS was about 180~250 nm with uniform distribution, confirmed by TEM image. The drug PRA in nanosuspensions possessed crystalline form evaluated via XRPD and DSC analysis. The solubility of PRA-LNS in water was 1.52 times larger than PRA raw drug; in vitro dissolution tests showed that PRA-LNS could dissolve completely within 5 min, which is a significant improvement compared to the raw drug. The relative bioavailability of PRA-LNS is 290.70% compared to the raw drug and 177.94% compared to the physical mixture.

Conclusions

PRA-LNS could easily re-disperse in water with increased solubility, enhanced oral bioavailability, and controllable production process.

     

Ursolic Acid Loaded PLGA Nanoparticles: <Emphasis Type="Italic">in vitro</Emphasis> and <Emphasis Type="Italic">in vivo</Emphasis> Evaluation to Explore Tumor Targeting Ability on B16F10 Melanoma Cell Lines

Purpose

Ursolic acid (UA), a pentacyclic triterpenoid extracted from plants, shows promising inhibitory effect in different tumor bearing cell lines. In the present study we fabricated UA loaded PLGA nanoparticles (UA-NPs) as the drug carrier and thoroughly evaluated in vitro and in vivo the differential tumor targeting effects of UA and UA-NPs in B16F10 melanoma cells.

Methods

Ursolic acid loaded PLGA nanoparticles were prepared by emulsion solvent evaporation technique and evaluated for particle size, polydispersity, zeta potential and drug release potency. MTT assay as well as flow cytometric and confocal microscopic analyses were done in B16F10 mouse melanoma cell lines. Formulations were labeled with technetium-99m to evaluate the biodistribution and perform scintigraphic imaging studies following intravenous administration in tumor bearing mice model.

Results

Single emulsification technique produced smooth spherical nanoparticles of small size with relatively narrow size distribution (154?±?4.56 nm). On B16F10 cell line, the formulation showed higher cytotoxicity compared to the free drug due to increased in vitro cellular uptake. The formulation was successfully radiolabeled and remained substantially (>90%) stable when incubated (37°C, 6 h) separately in normal saline or freshly collected rat serum or histidine solution. The radiolabeled UA-NPs exhibited slower blood clearance and comparatively high uptake in tumor region as evidenced by biodistribution and scintigraphic studies.

Conclusions

The in vitro and in vivo studies have proved the tumor targeting potential of UA-NPs in B16F10 melanoma cell lines.

     

Combination of Hyaluronic Acid Hydrogel Scaffold and PLGA Microspheres for Supporting Survival of Neural Stem Cells

Purpose

To develop a biomaterial composite for promoting proliferation and migration of neural stem cells (NSCs), as well as angiogenesis on the materials, to rescue central nervous system (CNS) injuries.

Methods

A delivery system was constructed based on cross-linked hyaluronic acid (HA) hydrogels, containing embedded BDNF and VEGF-loaded poly(lactic-co-glycolic acid) (PLGA) microspheres for controlled delivery and support for NSCs in the CNS. The surface morphologies were evaluated by SEM and AFM, mechanical property was investigated by rheological tests, and release kinetics were performed by ELISA. Bioactivity of released BDNF and VEGF was assessed by neuron and endothelial cell culture, respectively. Compatibility with NSCs was studied by immunofluorescent staining.

Results

Release kinetics showed the delivery of BDNF and VEGF from PLGA microspheres and HA hydrogel composite were sustainable and stable, releasing ~20–30% within 150 h. The bioactivities preserved well to promote survival and growth of the cells. Evaluation of structure and mechanical properties showed the hydrogel composite possessed an elastic scaffold structure. Biocompatibility assay showed NSCs adhered and proliferated well on the hydrogel.

Conclusions

Our created HA hydrogel/PLGA microsphere systems have a good potential for controlled delivery of varied biofactors and supporting NSCs for brain repair and implantation.

     

A Study on Toxicity of Chemically Synthesised Silver Nanoparticle on <Emphasis Type="Italic">Eudrilus eugeniae</Emphasis>

Objective

To evaluate the toxicity of the silver nanoparticle against earthworms - Eudrilus eugeniae, a model for soil organism.

Methods

Silver nanoparticles were synthesised by chemical reduction and further characterised by UV Visible Spectroscopy and FeSEM. Earthworms were allowed to interact with different concentrations of the synthesized silver nanoparticles. After exposure period, histology and inductively coupled plasma optical emission spectrometry (ICP-OES) were done to determine the accumulation and toxic effects exhibited by the nanoparticle on earthworms.

Results

The synthesized nanoparticle was found to be between the size of 180 and 200 nm. Histology studies revealed that silver nanoparticles to cause fibrosis, lipofuscin-like deposits and also gut disruption in earthworms.

Conclusion

Silver nanoparticles were found to be toxic to Eudrilus eugeniae, which was evidenced by histology.

     

Evaluation of Pharmacokinetics of Bioreducible Gene Delivery Vectors by Real-time PCR

Purpose

To investigate pharmacokinetics of reversibly stabilized DNA nanoparticles (rSDN) using a single-step lysis RT-PCR.

Methods

rSDN were prepared by coating bioreducible polycation/DNA polyplexes with multivalent N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers. Targeted polyplexes were formulated by linking cyclic RGD ligand (c(RGDyK)) to the HPMA surface layer of rSDN. The pharmacokinetic parameters in tumor-bearing mice were analyzed by PKAnalyst®.

Results

The pharmacokinetics of naked plasmid DNA, simple DNA polyplexes, rSDN, and RGD-targeted rSDN exhibited two-compartment model characteristics with area under the blood concentration–time curve (AUC) increasing from 1,102 ng?ml^?1?min^?1 for DNA to 3,501 ng?ml^?1?min^?1 for rSDN. Non-compartment model analysis revealed increase in mean retention time (MRT) from 4.5 min for naked DNA to 22.9 min for rSDN.

Conclusions

RT-PCR is a sensitive and convenient method suitable for analyzing pharmacokinetics and biodistribution of DNA polyplexes. Surface stabilization of DNA polyplexes can significantly extend their MRT and AUC compared to naked DNA. DNA degradation in rSDN in blood circulation, due to a combined effect of disulfide reduction and competitive reactions with charged molecules in the blood, contributes to DNA elimination.

     

Drug Delivery Nanoparticles with Locally Tunable Toxicity Made Entirely from a Light-Activatable Prodrug of Doxorubicin

Purpose

A major challenge facing nanoparticle-based delivery of chemotherapy agents is the natural and unavoidable accumulation of these particles in healthy tissue resulting in local toxicity and dose-limiting side effects. To address this issue, we have designed and characterized a new prodrug nanoparticle with controllable toxicity allowing a locally-delivered light trigger to convert the payload of the particle from a low to a high toxicity state.

Methods

The nanoparticles are created entirely from light-activatable prodrug molecules using a nanoprecipitation process. The prodrug is a conjugate of doxorubicin and photocleavable biotin (DOX-PCB).

Results

These DOX-PCB nanoparticles are 30 times less toxic to cells than doxorubicin, but can be activated to release pure therapeutic doxorubicin when exposed to 365 nm light. These nanoparticles have an average diameter of around 100 nm and achieve the maximum possible prodrug loading capacity since no support structure or coating is required to prevent loss of prodrug from the nanoparticle.

Conclusions

These light activatable nanoparticles demonstrate tunable toxicity and can be used to facilitate future therapy development whereby light delivered specifically to the tumor tissue would locally convert the nanoparticles to doxorubicin while leaving nanoparticles accumulated in healthy tissue in the less toxic prodrug form.

     

Effect of peptide length on the conjugation to the gold nanoparticle surface: a molecular dynamic study

Background

Gold nanoparticles now command a great deal of attention for medical applications. Despite the importance of nano-bio interfaces, interaction between peptides and proteins with gold surfaces is not still fully understood, especially in a molecular level.

Methods

In the present study computational simulation of adsorption of 20 amino acids, in three forms of mono-amino acid, homo di-peptide and homo tri-peptide, on the gold nanoparticles was performed by Gromacs using OPLSAA force field. The flexibility, stability, and size effect of the peptides on the gold nanoparticles were studied as well as the molecular structure of them.

Results

According to our results, adsorbed homo tri-peptides on the gold surface had more flexibility, more gyration, and the farthest distance from the GNP in comparison with homo di-peptides and mono-amino acids.

Conclusion

Our findings provide new insights into the precise control of interactions between amino acids anchored on the GNPs.

     

Biodegradable Nanoparticles Improve Oral Bioavailability of Amphotericin B and Show Reduced Nephrotoxicity Compared to Intravenous Fungizone®

Purpose

Amphotericin B (AMB), an effective antifungal and antileishmanial agent associated with low oral bioavailability (0.3%) and severe nephrotoxicity, was entrapped into poly(lactide-co-glycolide) (PLGA) nanoparticles to improve the oral bioavailability and to minimize the adverse effects associated with it.

Materials and Methods

The AMB-nanoparticles (AMB-NP) were prepared by nanoprecipitation method employing Vitamin E-TPGS as a stabilizer. In vitro release was carried out using membrane dialysis method. The in vitro hemolytic activity of AMB-NP was evaluated by incubation with red blood cells (RBCs). The acute nephrotoxicity profile and oral bioavailability of AMB-NP were evaluated in rats.

Results

The prepared AMB-NP formulation contained monodispersed particles in the size range of 165.6?±?2.9 nm with 34.5?±?2.1% entrapment at 10% w/w initial drug loading. AMB-NP formulation showed biphasic drug release, an initial rapid release followed by a sustained release. The AMB-NP formulation exerted lower hemolysis and nephrotoxicity as compared to Fungizone®. The relative oral bioavailability of the AMB-NP was found to be ～800% as compared to Fungizone®.

Conclusion

Together, these results offer a possibility of treating systemic fungal infection and leishmaniasis with oral AMB-NP, which could revolutionize the infectious disease treatment modalities.

     

Preparation of Drug-Loaded PLGA-PEG Nanoparticles by Membrane-Assisted Nanoprecipitation

Purpose

The aim of this work is to develop a scalable continuous system suitable for the formulation of polymeric nanoparticles using membrane-assisted nanoprecipitation. One of the hurdles to overcome in the use of nanostructured materials as drug delivery vectors is their availability at industrial scale. Innovation in process technology is required to translate laboratory production into mass production while preserving their desired nanoscale characteristics.

Methods

Membrane-assisted nanoprecipitation has been used for the production of Poly[(D,L lactide-co-glycolide)-co-poly ethylene glycol] diblock) (PLGA-PEG) nanoparticles using a pulsed back-and-forward flow arrangement. Tubular Shirasu porous glass membranes (SPG) with pore diameters of 1 and 0.2 μm were used to control the mixing process during the nanoprecipitation reaction.

Results

The size of the resulting PLGA-PEG nanoparticles could be readily tuned in the range from 250 to 400 nm with high homogeneity (PDI lower than 0.2) by controlling the dispersed phase volume/continuous phase volume ratio. Dexamethasone was successfully encapsulated in a continuous process, achieving an encapsulation efficiency and drug loading efficiency of 50% and 5%, respectively. The dexamethasone was released from the nanoparticles following Fickian kinetics.

Conclusions

The method allowed to produce polymeric nanoparticles for drug delivery with a high productivity, reproducibility and easy scalability.

     

Population-based normative values for the Western Ontario and McMaster (WOMAC<Superscript>®</Superscript>) osteoarthritis index and the Australian/Canadian (AUSCAN) hand osteoarthritis index functional subscales

Aim

To develop age- and gender-specific normative values for the physical function subscales of the WOMAC^® and AUSCAN Indices.

Methods

A scannable survey questionnaire capable of capturing WOMAC^® and AUSCAN Index and demographic information was developed, pre-tested, and distributed to a stratified random sample of 24,000 members of the Australian general public generated by the Australian Electoral Commission (AEC).

Results

Age- and gender-specific WOMAC^® and AUSCAN normative values were estimated based on approximately 5,500 subjects. Age-related differences were noted at the subscale level. In general, disability increased with age for all items and both Indices.

Conclusions

Normative values provide opportunity for benchmarking the health status of individuals against their age- and gender-matched peers in the general population. These normative values provide unique opportunities, for using the WOMAC^® and AUSCAN Indices in benchmarking applications, in both clinical practice and research.