Food-inspired innovations to improve the stability of active pharmaceutical ingredients.

Food-processing and pharmaceutical industries share a lot of stability issues against the same physical, chemical, and microbiological phenomena. They also share some solutions to improve the stability as the use of preservatives and packaging. Ecological concerns lead to the development of tremendous innovations in food. Some of these innovations could also be beneficial in the pharmaceutical domain. The objective of this review is to evaluate the potential application of these findings in the pharmaceutical field and the main limits in terms of toxicity, environmental, economic and regulatory issues. The principal factors influencing the shelf-life were highlighted through the description of the stability studies usually performed in the pharmaceutical industry (according to European guidelines). To counter those factors, different solutions are currently available as preservatives and specific packaging. They were described and debated with an overview of recent food innovations in each field. The limits of the current solutions in the pharmaceutical field and the innovation in the food field have inspired a critical pharmaceutical outlook. The active and intelligent packaging for active pharmaceutical ingredients of the future is imagined.

From the pharmaceutical to the clinical: the case for effervescent paracetamol in pain management. A narrative review.

OBJECTIVE: Paracetamol has an established place in the management of mild-to-moderate pain, but has certain limitations, including varying bioavailability, and potential hepatotoxicity if taken in overdose. Effervescent formulations may help to overcome these limitations. METHODS: Pubmed searches, with no limits on date or language, were conducted in February 2020. Further references were identified from the reference lists of retrieved articles, and from the authors' knowledge of the field. RESULTS: Effervescent formulations contain an organic acid (usually citric acid) and carbonate or bicarbonate salts (usually sodium bicarbonate). Upon contact with water, these react to form carbon dioxide, which facilitates the disintegration of the tablet and dissolution of the active drug. Moreover, sodium bicarbonate dose-dependently increases gastric emptying, which together with rapid dissolution facilitates drug absorption. In pharmacokinetic studies, effervescent formulations result in faster absorption of paracetamol than conventional oral formulations, and this translates into a faster onset of analgesia in clinical trials. Effervescent paracetamol has a favorable safety profile, with good tolerability. Importantly, the sodium content of some preparations does not appear to increase cardiovascular risk under real world conditions. Effervescent formulations may also offer advantages in terms of ease of administration and palatability. CONCLUSIONS: Effervescent formulations of paracetamol result in faster drug absorption, and hence more rapid analgesia, than oral tablets, and offer a favorable tolerability and safety profile. The use of such formulations may therefore help to promote appropriate use of paracetamol.

Understanding the Thermodynamic Mechanisms Leading to the Binding of Albumin to Lipid Nanocapsules.

Lipid nanocapsules (LNCs) are drug delivery platforms designed for different administration routes including intravenous delivery. Nanocarrier binding with plasma proteins such as albumin is an important factor that influences the pharmacokinetics of the drug and the drug delivery system. The aim of this paper was to characterize LNCs with different surface compositions and hydrophobicities to study their interactions with albumin: binary LNCs [oil-glyceryl trioctanoate (TG) and PEGylated surfactant macrogol 15-hydroxystearate (MHS)] and ternary LNCs (TG, MHS, and Span 80). Span was found to stabilize and decrease the LNC size. The formation of a stable LNC/albumin complex in the ground state was demonstrated. Thermodynamic parameters indicated that complex formation was exothermic and spontaneous, and the interactions involved van der Waals forces and hydrogen bond formation. Ternary LNCs showed higher affinity for albumin than did binary LNCs (affinity constant 10-fold higher). This study is the first report on the thermodynamic mechanisms that lead to the formation of a complex between albumin and organic nanoparticles with different surface architectures.

Updated Progress of Nanocarrier-Based Intranasal Drug Delivery Systems for Treatment of Brain Diseases.

Intranasal drug delivery is emerging as a reliable and promising pathway to deliver a wide range of therapeutic agents including small and large molecules, peptides and proteins, genes to the central nervous system for the treatment of brain diseases such as Alzheimer's disease, Parkinson's disease, depression, migraine, schizophrenia, and glioma. This presents noninvasive entry into the brain via direct nose-to-brain and/or indirect nose-to-blood-to-brain routes. Several nanocarrier-based strategies have been developed to transport therapeutic agents to the brain including nanoparticles, liposomes, and exosomes following intranasal delivery. However, the multiple barriers in nose-to-brain route - including rapid mucociliary clearance in the nasal cavity, enzyme degradation, and the blood-brain barrier (BBB) - pose serious challenges to brain-targeted drug delivery. Hence, very limited translation from the laboratory to the clinic has been achieved. The present review highlights the surface modification of nanocarriers with different strategies devoted to facilitate nose-to-brain delivery: prolonging retention time in the nasal cavity, improving penetration ability, and promoting brain targeting with ligands. Additionally, in vitro blood-brain barrier models, influencing an efficient study on intranasal delivery of therapeutics into the brain through indirect nose-to-blood-to-brain pathway, is discussed.

Polymeric Nanoparticles for Increasing Oral Bioavailability of Curcumin.

Despite the promising biological and antioxidant properties of curcumin, its medical applications are limited due to poor solubility in water and low bioavailability. Polymeric nanoparticles (NPs) adapted to oral delivery may overcome these drawbacks. Properties such as particle size, zeta potential, morphology and encapsulation efficiency were assessed. Then, the possibility of storing these NPs in a solid-state form obtained by freeze-drying, in vitro curcumin dissolution and cytocompatibility towards intestinal cells were evaluated. Curcumin-loaded Eudragit® RLPO (ERL) NPs showed smaller particle diameters (245 ± 2 nm) and better redispersibility after freeze-drying than either poly(lactic-co-glycolic acid) (PLGA) or polycaprolactone (PCL) NPs. The former NPs showed lower curcumin encapsulation efficiency (62%) than either PLGA or PCL NPs (90% and 99%, respectively). Nevertheless, ERL NPs showed rapid curcumin release with 91 ± 5% released over 1 h. The three curcumin-loaded NPs proposed in this work were also compatible with intestinal cells. Overall, ERL NPs are the most promising vehicles for increasing the oral bioavailability of curcumin.

Investigation of cationized triblock and diblock poly(ε-caprolactone)-co-poly(ethylene glycol) copolymers for oral delivery of enoxaparin: In vitro approach.

In this study, poly(ε-caprolactone)-co-poly(ethylene glycol) copolymers grafted with a cationic ligand, propargyltrimethyl ammonium iodide (PTA), to fabricate the cationized triblock (P(CatCLCL)2-PEG) and diblock (P(CatCLCL)-mPEG) copolymers were investigated their potential use for oral delivery of enoxaparin (ENX). Influences of various PTA contents and different structures of the copolymers on molecular characteristics, ENX encapsulation, particle characteristics, and capability of drug transport across Caco-2 cells were elucidated. The results showed that P(CatCLCL)2-PEG and P(CatCLCL)-mPEG copolymers self-aggregated and encapsulated ENX into spherical particles of ∼200-450nm. The increasing amount of PTA on the copolymers increased encapsulation efficiency of over 90%. The ENX release from both types of the cationized copolymer particles was pH-dependent which was retarded at pH 1.2 and accelerated at pH 7.4, supporting the drug protection in the acidic environment and possible release in the blood circulation. The toxicity of ENX-loaded particles on Caco-2 cells decreased when decreasing the amount of PTA. The triblock and diblock particles dramatically enhanced ENX uptake and transport across Caco-2 cells as compared to the ENX solution. However, the different structures of the copolymers slightly affected ENX transport. These results suggested that P(CatCLCL)2-PEG and P(CatCLCL)-mPEG copolymers would be potential carriers for oral delivery of ENX. STATEMENT OF SIGNIFICANCE: The anionic drugs such as proteins, peptides or polysaccharides are generally administered via invasive route causing patient incompliance and high cost of hospitalization. The development of biomaterials for non-invasive delivery of those drugs has gained much attention, especially for oral delivery. However, they have limitation due to non-biocompatibility and poor drug bioavailability. In this study, the novel poly(ε-caprolactone)-co-poly(ethylene glycol) copolymers grafted with propargyltrimethyl ammonium iodide, a small cationic ligand, were introduced to use as a carrier for oral delivery of enoxaparin, a highly negatively charged drug. The study showed that these cationized copolymers could achieve high enoxaparin entrapment efficiency, protect drug release in an acidic environment and enhance enoxaparin permeability across Caco-2 cells, the intestinal cell model. These characteristics of the cationized copolymers make them a potential candidate for oral delivery of anionic drugs for biomaterial applications.

One-week in vivo sustained release of a peptide formulated into in situ forming implants.

The LR12 peptide has been reported to reduce the size of infarct and improve both cardiac function and survival in myocardial infarction in murine models, after daily repeated intraperitoneal injections. In order to protect peptide from degrading and to prolong its release, in situ implants based on biocompatible biodegradable polymers were prepared and both in vitro and in vivo releases were evaluated after subcutaneous administration to Wistar rats. A progressive and complete release was obtained in vitro in 3 weeks. In vivo, a 7-day sustained release was demonstrated after administrating the formulation once; bioavailability was improved by protecting the peptide against the degradation identified as a dimerization through disulfide bond formation. As a conclusion, in situ forming formulations are a suitable alternative for the therapeutic use of this peptide.

Self-aggregation of cationically modified poly(ε-caprolactone)2-co-poly(ethylene glycol) copolymers: Effect of cationic grafting ligand and poly(ε-caprolactone) chain length.

Cationic copolymers have been attractive to investigate due to their potential to complexation with anionic drugs and expected to use in the pharmaceutical application. In this study, the modified poly(ε-caprolactone)2-co-poly(ethylene glycol) copolymers (P(CL)2-PEG) were successfully synthesized by click reaction. The amount of small molecular cationic ligand, propargyltrimethyl ammonium iodide, was varied and grafted onto various mole ratios of P(CL) to PEG. The effects of P(CL) chain length and amount of the grafting cationic ligand on physicochemical properties of polymers and particles were studied. The number-average molecular weights of the copolymers grafted with cationic ligand were found ranging between 10,000 and 23,000g/mol as investigated by NMR. From DSC study, the results showed that the grafting ligand affected thermal behaviors of the copolymers by increasing the glass transition temperature and decreasing the melting temperature of the copolymers. Furthermore, these cationic copolymers could self-aggregate with their critical aggregation concentration depending on mole ratios of hydrophilic to hydrophobic portions. The particles containing higher amounts of the cationic ligand tended to aggregate in both acidic and basic pH environment and at high salt concentration. Additionally, particle size, size distribution (PdI), and morphology of self-assembling particles varied depending on P(CL) chain length and the amount of the grafting cationic ligand. The synthesized cationic copolymer showed a capability to encapsulate a high negatively charged drug, enoxaparin, with an encapsulation efficiency of 87%. After drug incorporation, the particles substantially changed in size, shape, PdI, and zeta potential to become more suitable for drug delivery. These cationic copolymers with flexible properties will be the candidate for further development as carriers for the delivery of negatively charged drugs.

Polymer nanocomposites enhance S-nitrosoglutathione intestinal absorption and promote the formation of releasable nitric oxide stores in rat aorta.

Alginate/chitosan nanocomposite particles (GSNO-acNCPs), i.e. S-nitrosoglutathione (GSNO) loaded polymeric nanoparticles incorporated into an alginate and chitosan matrix, were developed to increase the effective GSNO loading capacity, a nitric oxide (NO) donor, and to sustain its release from the intestine following oral administration. Compared with free GSNO and GSNO loaded nanoparticles, GSNO-acNCPs promoted 2.7-fold GSNO permeation through a model of intestinal barrier (Caco-2 cells). After oral administration to Wistar rats, GSNO-acNCPs promoted NO storage into the aorta during at least 17h, as highlighted by (i) a long-lasting hyporeactivity to phenylephrine (decrease in maximum vasoconstrictive effect of aortic rings) and (ii) N-acetylcysteine (a thiol which can displace NO from tissues)-induced vasodilation of aorxxtic rings preconstricted with phenylephrine. In conclusion, GSNO-acNCPs enhance GSNO intestinal absorption and promote the formation of releasable NO stores into the rat aorta. GSNO-acNCPs are promising carriers for chronic oral application devoted to the treatment of cardiovascular diseases.

Albumin as a carrier for NO delivery: preparation, physicochemical characterization, and interaction with gold nanoparticles.

BACKGROUND: Nitric oxide (NO) is a gaseous transmitter playing numerous physiological roles and characterized by a short half-life. Its binding to endogenous thiols increases its stability, facilitating its storage and transport. The purpose of this study was to investigate the nitrosated serum albumin (SA-SNO) and to provide a reference for its easy preparation for further use in in vitro studies. METHODS: Serum albumin (SA) was S-nitrosated by reacting with (i) NaNO2 in acidic medium; (ii) different low-molecular weight S-nitrosothiols (RSNO) (S-nitrosocysteine (CysNO), S-nitrosoglutathione (GSNO), and S,S'-dinitrosobucillamine (Buc(NO)2)); and (iii) diethylamine NONOate (DEA/NO). SA-SNO was purified by size exclusion chromatography and the S-nitrosation site and the rate were studied by mass spectrometry and Griess-Saville assay, respectively. Then, SA-SNO was characterized by spectrofluorimetry, dynamic light scattering, and circular dichroism. Finally, SA-SNO reactivity with citrate stabilized gold nanoparticles (AuNP-citrate) was investigated via determination of NO release. RESULTS: S-nitrosation rates of SA were 90.1 ± 3.3, 76.8 ± 2.7, 80.3 ± 3.2, 84.8 ± 5.0, and 15.4 ± 1.9% (n = 5), when SA was reacted with acidified NaNO2, CysNO, GSNO, Buc(NO)2, and DEA/NO, respectively. The physicochemical characterization indicated that the resulting product corresponded to a mono-S-nitrosothiol (on cysteine-34), and the conformational construction remained unchanged. Stability studies showed that the NO content was preserved over 1 week. AuNP-citrate reacted with SA-SNO with increase of its hydrodynamic diameter but preservation of SNO bond. CONCLUSIONS: SA-SNO prepared and stored under the reported conditions affords a well-defined reference suitable for in vitro studies.

In Situ Microparticles Loaded with S-Nitrosoglutathione Protect from Stroke.

Treatment of stroke, especially during the first hours or days, is still lacking. S-nitrosoglutathione (GSNO), a cerebroprotective agent with short life time, may help if administered early with a sustain delivery while avoiding intensive reduction in blood pressure. We developed in situ forming implants (biocompatible biodegradable copolymer) and microparticles (same polymer and solvent emulsified with an external oily phase) of GSNO to lengthen its effects and allow cerebroprotection after a single subcutaneous administration to Wistar rats. Arterial pressure was recorded for 3 days (telemetry, n = 14), whole-blood platelet aggregation up to 13 days (aggregometry, n = 58), and neurological score, cerebral infarct size and edema volume for 2 days after obstruction of the middle cerebral artery by autologous blood clots (n = 30). GSNO-loaded formulations (30 mg/kg) induced a slighter and longer hypotension (-10 vs. -56 ± 6 mmHg mean arterial pressure, 18 h vs. 40 min) than free GSNO at the same dose. The change in pulse pressure (-50%) lasted even up to 42 h for microparticles. GSNO-loaded formulations (30 mg/kg) prevented the transient 24 h hyper-aggregability observed with free GSNO and 7.5 mg/kg-loaded formulations. When injected 2 h after stroke, GSNO-loaded microparticles (30 mg/kg) reduced neurological score at 24 (-62%) and 48 h (-75%) vs. empty microparticles and free GSNO 7.5 mg/kg and, compared to free GSNO, divided infarct size by 10 and edema volume by 8 at 48 h. Corresponding implants reduced infarct size and edema volume by 2.5 to 3 times. The longer (at least 2 days) but slight effects on arterial pressures show sustained delivery of GSNO-loaded formulations (30 mg/kg), which prevent transient platelet hyper-responsiveness and afford cerebroprotection against the consequences of stroke. In conclusion, in situ GSNO-loaded formulations are promising candidates for the treatment of stroke.

Development of enoxaparin sodium polymeric microparticles for colon-specific delivery.

BACKGROUND AND AIMS: Recent studies have shown that low molecular weight heparins are effective in the treatment of inflammatory bowel disease. Therefore, there is considerable interest in the development of an oral colonic delivery pharmaceutical system allowing targeted release of heparin in the inflamed tissue. The objective of this study was to prepare microparticles for the oral administration and colonic release of enoxaparin and to evaluate the influence of certain formulation factors on their characteristics. METHODS: Microparticles were prepared by water/oil/water double emulsion technique followed by solvent evaporation. The influence of several formulation factors on the characteristics of microparticles were evaluated. The formulation factors were alginate concentration in the inner aqueous phase, polymer (Eudragit(®) FS 30D and Eudragit(®) RS PO) concentration in the organic phase and ratios between the two polymers. The microparticles were characterized in terms of morphology, size, entrapment efficiency and enoxaparin release. RESULTS: The results showed that increasing sodium alginate percentage reduced the encapsulation efficiency of enoxaparin and accelerated enoxaparin release. Regarding the influence of the two polymers, reducing polymer concentration in the organic phase led to a smaller size of microparticles, a lower entrapment efficiency and an important retardation of enoxaparin release. The formulation prepared with Eudragit(®) FS 30D limited the release to a maximum of 3% in gastric simulated environment, a specific characteristic of oral systems for colonic delivery, and fulfilled our objective to delay the release. CONCLUSIONS: Microparticles prepared with Eudragit(®) FS 30D represent a suitable and potential oral system for the colonic delivery of enoxaparin.

Polymer nanocomposite particles of S-nitrosoglutathione: A suitable formulation for protection and sustained oral delivery.

S-nitrosoglutathione (GSNO) is a nitric oxide (NO) donor with therapeutic potential for cardiovascular disease treatment. Chronic oral treatment with GSNO is limited by high drug sensitivity to the environment and limited oral bioavailability, requiring the development of delivery systems able to sustain NO release. The present work describes new platforms based on polymer nanocomposite particles for the delivery of GSNO. Five types of optimized nanocomposite particles have been developed (three based on chitosan, two based on alginate sodium). Those nanocomposite particles encapsulate GSNO with high efficiency from 64% to 70% and an average size of 13 to 61 µm compatible with oral delivery. Sustained release of GSNO in vitro was achieved. Indeed, chitosan nanocomposites discharged their payload within 24h; whereas alginate nanocomposites released GSNO more slowly (10% of GSNO was still remaining in the dosage form after 24h). Their cytocompatibility toward intestinal Caco-2 cells (MTT assay) was acceptable (IC50: 6.07 ± 0.07-9.46 ± 0.08 mg/mL), demonstrating their suitability as oral delivery systems for GSNO. These delivery systems presented efficient GSNO loading and sustained release as well as cytocompatibility, showing their promise as a means of improving the oral bioavailability of GSNO and as a potential new treatment.

[Counterfeit and Falsified Drugs: an Overview]. / Trafic de faux médicaments : panorama 2014.

If the traffic of fake medicines may represent an economic threat for the pharmaceutical industry, it can also be responsible of safety concerns for patients. Despite fake drugs represent a real threat for public health, the intended punishments are until now only based on intellectual property rights. Estimated to generate more than 55 billion euros per year, the traffic of falsified drugs varies from a country to another one. Indeed, the proportion of falsified drugs ranges from 1% in industrialized countries with a regulated and controlled distribution system to 60% of medicines in some developing countries. Currently, the measures developed to limit this traffic concern five main areas: legislation / regulation, cooperation, enforcement, technology and communication. Communication actions should be performed to inform health professionals as the populations about the risks of using drugs purchased outside the legal drug market.

Doxorubicin-loaded glycyrrhetinic acid modified recombinant human serum albumin nanoparticles for targeting liver tumor chemotherapy.

Due to overexpression of glycyrrhetinic acid (GA) receptor in liver cancer cells, glycyrrhetinic acid modified recombinant human serum albumin (rHSA) nanoparticles for targeting liver tumor cells may result in increased therapeutic efficacy and decreased adverse effects of cancer therapy. In this study, doxorubicin (DOX) loaded and glycyrrhetinic acid modified recombinant human serum albumin nanoparticles (DOX/GA-rHSA NPs) were prepared for targeting therapy for liver cancer. GA was covalently coupled to recombinant human serum albumin nanoparticles, which could efficiently deliver DOX into liver cancer cells. The resultant GA-rHSA NPs exhibited uniform spherical shape and high stability in plasma with fixed negative charge (∼-25 mV) and a size about 170 nm. DOX was loaded into GA-rHSA NPs with a maximal encapsulation efficiency of 75.8%. Moreover, the targeted NPs (DOX/GA-rHSA NPs) showed increased cytotoxic activity in liver tumor cells compared to the nontargeted NPs (DOX/rHSA NPs, DOX loaded recombinant human serum albumin nanoparticles without GA conjugating). The targeted NPs exhibited higher cellular uptake in a GA receptor-positive liver cancer cell line than nontargeted NPs as measured by both flow cytometry and confocal laser scanning microscopy. Biodistribution experiments showed that DOX/GA-rHSA NPs exhibited a much higher level of tumor accumulation than nontargeted NPs at 1 h after injection in hepatoma-bearing Balb/c mice. Therefore, the DOX/GA-rHSA NPs could be considered as an efficient nanoplatform for targeting drug delivery system for liver cancer.

Time lasting S-nitrosoglutathione polymeric nanoparticles delay cellular protein S-nitrosation.

Physiological S-nitrosothiols (RSNO), such as S-nitrosoglutathione (GSNO), can be used as nitric oxide (NO) donor for the treatment of vascular diseases. However, despite a half-life measured in hours, the stability of RSNO, limited by enzymatic and non-enzymatic degradations, is too low for clinical application. So, to provide a long-lasting effect and to deliver appropriate NO concentrations to target tissues, RSNO have to be protected. RSNO encapsulation is an interesting response to overcome degradation and provide protection. However, RSNO such as GSNO raise difficulties for encapsulation due to its hydrophilic nature and the instability of the S-NO bound during the formulation process. To our knowledge, the present study is the first description of the direct encapsulation of GSNO within polymeric nanoparticles (NP). The GSNO-loaded NP (GSNO-NP) formulated by a double emulsion process, presented a mean diameter of 289 ± 7 nm. They were positively charged (+40 mV) due to the methacrylic acid and ethylacrylate polymer (Eudragit® RL) used and encapsulated GSNO with a satisfactory efficiency (i.e. 54% or 40 mM GSNO loaded in the NP). In phosphate buffer (37 °C; pH 7.4), GSNO-NP released 100% of encapsulated GSNO within 3h and remained stable still 6h. However, in contact with smooth muscle cells, maximum protein nitrosation (a marker of NO bioavailability) was delayed from 1h for free GSNO to 18h for GSNO-NP. Therefore, protection and sustained release of NO were achieved by the association of a NO donor with a drug delivery system (such as polymeric NP), providing opportunities for vascular diseases treatment.

PLGA in situ implants formed by phase inversion: critical physicochemical parameters to modulate drug release.

In situ forming implants (ISI) based on phase separation by solvent exchange represent an attractive alternative to conventional preformed implants and microparticles for parenteral applications. They are indeed easier to manufacture and their administration does not require surgery, therefore improving patient compliance. They consist of polymeric solutions precipitating at the site of injection and thus forming a drug eluting depot. Drug release from ISI is typically divided into three phases: burst during precipitation of the depot, diffusion of drug through the polymeric matrix and finally drug release by system degradation. This review gives a comprehensive overview on (i) the theoretical bases of these three phases, (ii) the parameters influencing them and (iii) the remaining drawbacks which have to be addressed to enlarge their commercial opportunities. Indeed, although some of them are already commercialized, ISI still suffer from limitations: mainly lack of reproducibility in depot shape, burst during solidification and potential toxicity. Nevertheless, depending on the targeted therapeutic application, these shortcomings may be transformed into advantages. As a result, keys are given in order to tailor these formulations in view of the desired application so that ISI could gain further clinical importance in the following years.

Are in situ formulations the keys for the therapeutic future of S-nitrosothiols?

S-nitrosoglutathione (GSNO) and S-nitroso-N-acetylpenicillamine (SNAP) were formulated into in situ forming implants (ISI) and microparticles (ISM) using PLGA and either N-methyl-2-pyrrolidone (NMP) or triacetin. Physicochemical characterization was carried out, including the study of matrix structure and degradation. A strong correlation between drug hydrophobicity and the in vitro release profiles was observed: whatever the formulation, GSNO and SNAP were completely released after ca. 1 day and 1 week, respectively. Then, selected formulations (i.e., SNAP-loaded NMP formulations) demonstrated the ability to sustain the vasodilation effect of SNAP, as shown by monitoring the arterial pressure (telemetry) of Wistar rats after subcutaneous injection. Both ISI and ISM injections resulted in a 3-fold extended decrease in pulse arterial pressure compared with the unloaded drug, without significant decrease in the mean arterial pressure. Hence, the results emphasize the suitability of these formulations as drug delivery systems for S-nitrosothiols, widening their therapeutic potential.

Role of gold nanoparticles capping density on stability and surface reactivity to design drug delivery platforms.

Five-nanometer sized gold nanoparticles (Au NPs) stabilized with citrate ions have been reacted with various amounts of dihydrolipoic acid (DHLA) (×28, ×56, ×140, ×222, relative to Au NPs). Ligand exchange between citrate and the dithiol resulted in DHLA-capped Au NPs, whose degree of inertia was found to be related to the density of capping. The results revealed the importance of DHLA coating density to enhance the colloidal stability and modulate the reactivity toward free radicals and proteins of biological relevance. Thus, Au NPs capped with the highest amount of DHLA were found to be the ones that were, first, the most resistant to environmental changes, then characterized by the lowest residual catalytic reactivity of their metallic core, and finally the lowest interacting with proteins through nonspecific adsorption. The physicochemical properties conferred to Au NPs prepared with the ×222 excess should be valuable for further pharmaceutical development of nanoparticle platforms.

Engineered nanoparticulate drug delivery systems: the next frontier for oral administration?

For the past few decades, there has been a considerable research interest in the area of oral drug delivery using nanoparticle (NP) delivery systems as carriers. Oral NPs have been used as a physical approach to improve the solubility and the stability of active pharmaceutical ingredients (APIs) in the gastrointestinal juices, to enhance the intestinal permeability of drugs, to sustain and to control the release of encapsulated APIs allowing the dosing frequency to be reduced, and finally, to achieve both local and systemic drug targeting. Numerous materials have been used in the formulation of oral NPs leading to different nanoparticulate platforms. In this paper, we review various aspects of the formulation and the characterization of polymeric, lipid, and inorganic NPs. Special attention will be dedicated to their performance in the oral delivery of drug molecules and therapeutic genes.