Design and production of nanoparticles formulated from nano-emulsion templates-a review

A considerable number of nanoparticle formulation methods are based on nano-emulsion templates, which in turn are generated in various ways. It must therefore be taken into account that active principles and drugs encapsulated in nanoparticles can potentially be affected by these nano-emulsion formulation processes. Such potential differences may include drug sensitivity to temperature, high-shear devices, or even contact with organic solvents. Likewise, nano-emulsion formulation processes must be chosen in function of the selected therapeutic goals of the nano-carrier suspension and its administration route. This requires the nanoparticle formulation processes (and thus the nano-emulsion formation methods) to be more adapted to the nature of the encapsulated drugs, as well as to the chosen route of administration. Offering a comprehensive review, this paper proposes a link between nano-emulsion formulation methods and nanoparticle generation, while at the same time bearing in mind the above-mentioned parameters for active molecule encapsulation. The first part will deal with the nano-emulsion template through the different formulation methods, i.e. high energy methods on the one hand, and low-energy ones (essentially spontaneous emulsification and the phase inversion temperature (PIT) method) on the other. This will be followed by a review of the different families of nanoparticles (i.e. polymeric or lipid nanospheres and nanocapsules) highlighting the links (or potential links) between these nanoparticles and the different nano-emulsion formulation methods upon which they are based

Understanding the adsorption of salmon calcitonin, antimicrobial peptide AP114 and polymyxin B onto lipid nanocapsules

The adsorption of therapeutic molecules, e.g., peptides, onto nanocarriers is influenced by the properties of the carrier, adsorbed molecule and continuous phase. Hence, through changes in the composition of the nanocarrier and the medium, it should be possible to tune the system to make it capable of efficiently adsorbing peptides. The adsorption of calcitonin, antimicrobial peptide AP114 and polymyxin B onto lipid nanocapsules was investigated. The adsorption data were fitted to a Langmuir isotherm. Dynamic light scattering and laser Doppler velocimetry were used to investigate the changes in the hydrodynamic diameter and zeta potential, respectively, of the nanocarrier. The peptide adsorption was primarily governed by electrostatic forces; however, even without the presence of an ionisable surfactant, a significant amount of each tested molecule was adsorbed due to the enormous surface area of the nanocarriers and to peptide-nanocarrier interactions. The addition of an ionisable lipophilic surfactant, lecithin, improved the adsorption yield, which reached values of up to 100%. The adsorption yield and the properties of the nanocarrier, particularly the zeta potential, depended on the carrier and peptide concentrations and their mixing ratio. The adsorption of all tested molecules obeyed the Langmuir model over a limited concentration range

Lipid-based nanoformulations for peptide delivery

Nanoformulations have attracted a lot of attention because of their size-dependent properties. Among the array of nanoformulations, lipid nanoformulations (LNFs) have evoked increasing interest because of the advantages of their high degree of biocompatibility and versatility. The performance of lipid nanoformulations is greatly influenced by their composition and structure. Therapeutic peptides represent a growing share of the pharmaceutical market. However, the main challenge for their development into commercial products is their inherent physicochemical and biological instability. Important peptides such as insulin, calcitonin and cyclosporin A have been incorporated into LNFs. The association or encapsulation of peptides within lipid-based carriers has shown to protect the labile molecules against enzymatic degradation. This review describes strategies used for the formulation of peptides and some methods used for the assessment of association efficiency. The advantages and drawbacks of such carriers are also described

Particular conductive behaviors of emulsion phase inverting

This paper presents a study of the phenomenon of emulsion phase inversion through a thorough follow-up of emulsion and microemulsion electrical conductivity. A model nonionic surfactant, C18E6, was used in order to study a general case and emphasize the general aspect of this work. This study mainly discloses the experimental origins of the peak-shaped conductivity irregularity within the emulsion inversion. This phenomenon is then shown to be linked to the formation of myelin-like liquid crystals, observed at equilibrium between slide and coverslip, by temperature-monitored polarizing microscopy. The potential links between these new results and the phase inversion temperature method for generating nano-emulsions were also tackled. Finally, this paper provides an original approach, new insights into the phenomena arising when emulsions undergo a phase inversion, in terms of electrical conductivity, liquid crystal formation, phase diagrams, and nonionic surfactant behavior

Reverse micelle-lipid nanocapsules: a novel strategy for drug delivery of the plectasin derivate AP138 antimicrobial peptide

Introduction: Resistance to traditional antibiotics is an increasingly serious problem. Antimicrobial peptides (AMPs) have emerged as a new therapeutic class with great potential against infectious diseases, as they are less prone to induce resistance. Nanotechnology-based delivery strategies can improve the efficiency and stability of AMPs, particularly against proteolytic degradation. Lipid nanocapsules (LNCs) are a new generation of biomimetic nanocarriers and were used in this study to deliver peptides. Methods: AMP-loaded reverse micelles (RM) were developed and incorpo rated into LNCs by the phase inversion process and the antimicrobial activity of the AMPs-loaded LNC was evaluated by the minimum inhibitory concentration method. We studied the activity of AMP solutions and AMP-loaded LNCs against Gram-positive and Gram-negative bacterial strains and then evaluated the encapsulation of a new cationic AMP called AP138. Finally, we analyzed the effect of enzymatic attack on AP138 and AP138-RM-LNCs after incubation with trypsin. Results: AP138 was efficiently encapsulated in the LNCs (encapsulation efficiency = 97.8% at a drug loading of 0.151%), resulting in protection against degradation by proteases and the preservation of antimicrobial activity against , including . Conclusion: This study shows that RM-LNCs are an excellent candidate system to deliver AMPs

Reverse micelle-loaded lipid nanocarriers: A novel drug delivery system for the sustained release of doxorubicin hydrochloride

In this study, we are pioneering new nanotechnology for the encapsulation of anticancer drugs (doxorubicin (DOX) and/or docetaxel (DOCE)), whatever their solubility and water affinity. The purpose of this study is to highlight the potential of this recently patented technology, by carrying out a thorough physicochemical characterisation of these multiscaled nanocarriers, followed by the study of an encapsulation and release model of hydrophilic anticancer drug. The formulation process is based on a low-energy nano-emulsification method and allows the generation of a structure composed of oil-based nanocarriers loaded with reverse micelles. Thanks to this, hydrophilic contents can be solubilised in the oily core of this kind of nano-emulsion along with lipophilic content. The results emphasise some original structure particularities due to the multistep formulation process, and the diffusion-based behaviour revealed for the DOX release profile that is shown to be intimately linked to the morphology of the particles

Post-insertion into Lipid NanoCapsules (LNCs): From experimental aspects to mechanisms

Over the last decade, Lipid NanoCapsules (LNCs) have been intensively used as effective drug delivery systems; they are classically prepared using a phase-inversion method. Following formulation of the LNCs, the molecular insertion of commercially-available disteraoylphosphatidylethanolamine-peg amphiphiles is performed into the LNC shell, using a post-insertion method, more classically applied with liposomes. The subsequent LNC interfacial modifications are investigated by using size and electrokinetic measurements. More particularly, the length and the nature of the hydrophilic part of the post-inserted surfactant are modified. The results are discussed in order to improve our understanding of post-insertion mechanisms

New intravenous calcimimetic agents: New options, new problems. an example on how clinical, economical and ethical considerations affect choice of treatment

Background. Dialysis treatment is improving, but several long-term problems remain unsolved, including metabolic bone disease linked to chronic kidney disease (CKD-MBD). The availability of new, efficacious but expensive drugs (intravenous calcimimetic agents) poses ethical problems, especially in the setting of budget limitations. Methods. Reasons of choice, side effects, biochemical trends were discussed in a cohort of 15 patients (13% of the dialysis population) who stared treatment with intravenous calcimimetics in a single center. All patients had previously been treated with oral calcimimetic agents; dialysis efficacy was at target in 14/15; hemodiafiltration was employed in 10/15. Median Charlson Comorbidity Index was 8. The indications were discussed according to the principlist ethics (beneficience, non maleficience, justice and autonomy). Biochemical results were analyzed to support the clinical-ethical choices. Results. In the context of a strict clinical and biochemical surveillance, the lack of side effects ensured “non-maleficence”; efficacy was at least similar to oral calcimimetic agents, but tolerance was better. Autonomy was respected through a shared decision-making model; all patients appreciated the reduction of the drug burden, and most acknowledged better control of their biochemical data. The ethical conflict resides in the balance between the clinical “beneficience, non-maleficience” advantage and “justice” (economic impact of treatment, potentially in attrition with other resources, since the drug is expensive and included in the dialysis bundle). The dilemma is more relevant when a patient’s life expectancy is short (economic impact without clear clinical advantages), or when non-compliance is an issue (unclear advantage if the whole treatment is not correctly taken). Conclusions. In a context of person-centered medicine, autonomy, beneficence and non-maleficence should weight more than economic justice. While ethical discussions are not aimed at finding “the right answer” but asking “the right questions”, this example can raise awareness of the importance of including an ethical analysis in the choice of “economically relevant” drugs