Lipid Formulations Research Articles

Promising Nanocarriers to Enhance Solubility and Bioavailability of Cannabidiol for a Plethora of Therapeutic Opportunities.

In recent years, the interest in cannabidiol (CBD) has increased because of the lack of psychoactive properties. However, CBD has low solubility and bioavailability, variable pharmacokinetics profiles, poor stability, and a pronounced presystemic metabolism. CBD nanoformulations include nanosuspensions, polymeric micelles and nanoparticles, hybrid nanoparticles jelled in cross-linked chitosan, and numerous nanosized lipid formulations, including nanostructured lipid carriers, vesicles, SNEEDS, nanoemulsions, and microemulsions. Nanoformulations have resulted in high CBD solubility, encapsulation efficiency, and stability, and sustained CBD release. Some studies assessed the increased Cmax and AUC and decreased Tmax. A rational evaluation of the studies reported in this review evidences how some of them are very preliminary and should be completed before performing clinical trials. Almost all the developed nanoparticles have simple architectures, are well-known and safe nanocarriers, or are even simple nanosuspensions. In addition, the conventional routes of administration are generally investigated. As a consequence, many of these studies are almost ready for forthcoming clinical translations. Some of the developed nanosystems are very promising for a plethora of therapeutic opportunities because of the versatility in terms of the release, the crossing of physiological barriers, and the number of possible routes of administration.

Safety and immunogenicity of the Na-APR-1 hookworm vaccine in infection-naïve adults

BackgroundThe Necator americanus hemoglobinase, aspartic protease-1 (Na-APR-1), facilitates the ability of adult hookworms to parasitize the intestine of their human hosts. A recombinant version of APR-1 protected laboratory animals against hookworm infection by inducing neutralizing antibodies that block the protein’s enzymatic activity and thereby impair blood feeding. A catalytically inactive version of the wild-type hemoglobinase (Na-APR-1(M74)) was expressed by infiltrating Nicotiana benthamiana tobacco plants with an Agrobacterium tumefaciens strain engineered to express the vaccine antigen, which was adjuvanted with aluminum hydroxide adjuvant (Alhydrogel). MethodsAn open-label dose-escalation Phase 1 clinical trial was conducted in 40 healthy, hookworm-naïve adult volunteers in the United States. Participants received 30 or 100 µg of recombinant Na-APR-1(M74) with Alhydrogel or with Alhydrogel co-administered with one of two doses (2.5 or 5.0 µg) of an aqueous formulation of Glucopyranosyl Lipid A (GLA-AF). Intramuscular injections of study vaccine were administered on days 0, 56, and 112. ResultsNa-APR-1(M74)/Alhydrogel was well-tolerated; the most frequent adverse events were mild or moderate injection site tenderness and pain, and mild or moderate nausea and headache. No serious adverse events or adverse events of special interest related to vaccination were observed. Significantly higher levels of antigen-specific IgG antibodies were induced in those who received 100 µg Na-APR-1(M74) than those who received 30 µg of antigen. Adding GLA-AF to Na-APR-1(M74)/Alhydrogel resulted in higher levels of IgG against Na-APR-1(M74) in both the 30 and 100 µg Na-APR-1(M74) groups in comparison to the non-GLA formulations at the same antigen dose. ConclusionsVaccination of hookworm-naïve adults with recombinant Na-APR-1(M74) was well-tolerated, safe, and induced significant IgG responses against the vaccine antigen Na-APR-1(M74). Given these favorable results, clinical trials of this product were initiated in hookworm-endemic areas of Gabon and Brazil.

Vitamin D3 affects browning of white adipocytes by regulating autophagy via PI3K/Akt/mTOR/p53 signaling in vitro and in vivo.

Promoting brown fat-like phenotype in white adipose tissue has been a promising strategy for the treatment of obesity. Vitamin D3 (VD3) has been indicated to affect differentiation of white and brown adipocytes. Nevertheless, its potential mechanism involved in obesity development is unclear. Oil red O staining was utilized to detect lipid formation in 3T3-L1 adipocytes. CKK-8 assay was used for measurement of cell viability. RT-qPCR and western blotting were implemented for expression detection of markers for white adipocyte browning, autophagy- and PI3K/Akt/mTOR/p53 signaling-associated proteins. Immunofluorescence staining was conducted for assessment of autophagy. An obese mouse model was established by high-fat VD deficient diet. VD3 suppressed lipid formation in 3T3-L1 adipocytes. VD3 downregulated markers for white adipocyte browning (PPAR-γ, PGC-1α, UCP1), enhanced autophagy, activated p53 signaling and inactivated PI3K/Akt/mTOR signaling in 3T3-L1 adipocytes and HF-VDD-induced mice. VD3 suppressed HF-VDD-induced weight gain in mice. VD3 inhibits the expression of markers for white adipocyte browning in vitro and in vivo by enhancing autophagy and regulating PI3K/Akt/mTOR/p53 signaling pathway.

Lipid–Protein Oxidation and In Vitro Digestibility of Fermented Turkey Sausages as Affected by Lipid Formulation

AbstractThis research investigates the effects of using different lipid formulations (100% beef fat, 85% beef fat+15% olive oil, or 70% beef fat+30% olive oil) in fermented turkey sausages on protein–lipid oxidation, in vitro digestibility, and related quality parameters. The use of olive oil results in decreased fat content, modified fatty acid profile, and increased pH value, acidity, and water activity, besides changes are recorded in instrumental quality and sensory features. Lipid oxidation is higher in samples with 30% olive oil than in the others. Carbonyl content increases depending on oil level and storage time. α‐aminoadipic semialdehyde is only detected in products containing 30% olive oil and their concentrations increased with storage. γ‐glutamic semialdehyde also increases by olive oil inclusion, but decrements are recorded during storage. Increasing olive oil results in increased pepsin digestibility but losses are recorded in both pepsin and trypsin plus α‐chymotrypsin digestion rates during storage.Practical applications: Inclusion of vegetable oils into meat product formulations has been preferred recently to supply healthier products, but in this situation, oxidative deterioration again becomes a considerable problem affecting overall quality. The data obtained from the present work wil contribute to understand the impacts of formulation and processing operations on the formation of oxidation products and change in digestibility, thereby to pioneer further research on this topic.

BIOAVAILABILITY ENHANCEMENT OF REPAGLINIDE USING NANO LIPID CARRIER: PREPARATION CHARACTERIZATION AND IN VIVO EVALUATION

Objective: The aim of this study to manufacture the prolonged release lipid nanoparticle (Solid lipid nanoparticle and nanostructure lipid carrier) of repaglinide for enhance the oral bioavailability. Methods: Solid lipid nanoparticles (SLN) and Nanostructured lipid carriers (NLC) were prepared by slight modification in the solvent diffusion method. The core material used as cetyl alcohol while blend with oleic acid was used in the preparation of NLC dispersion. Tween 80 were utilized as a Surfactant and lecithin as a cosurfactant in both types of lipid formulation. Lipid nanoparticles were characterized for size distribution, entrapment parameter, zeta potential, surface morphology, in vitro drug release and stability study. Pharmacodynamic study were also performed to evaluate the antidiabetic activity of repaglinide-loaded lipid nanodispersion. Results: It was observed that lipid matrix-based SLN and NLC having significant particle size (157.8±15.8 nm for NLC and 238.4±48.2 nm for SLN dispersion), entrapment efficacy 79.82±0.84% for NLC and 72.04±1.03% for SLN dispersion. Zeta potential report was also clarifying that the formulation is in a stable state for a prolong time. SEM study size distribution of particle as evaluated by Malvern instrument. The formulation was also confirmed to be stable after 180 d of storage, according to the data from the stability study. The in vivo antidiabetic assessment showed that Repaglinide-loaded SLN and NLC dispersion were able to reduce the blood sugar level. Interestingly, in the case of the RPG-SLN, RPG-NLC-I and RPG-NLC-II groups, and the average blood sugar values at all-time intervals were significantly less than that of the basal glucose value (p<0.05). Conclusion: The prepared SLN and NLC dispersion having the ability to control the release and make nano formulation suitable to resolve poor bioavailability of repaglinide.

Inhibition of polyploidization in Pten-deficient livers reduces steatosis.

The tumour suppressor PTEN is a negative regulator of the PI3K/AKT signalling pathway. Liver-specific deletion of Pten in mice results in the hyper-activation PI3K/AKT signalling accompanied by enhanced genome duplication (polyploidization), marked lipid accumulation (steatosis) and formation of hepatocellular carcinomas. However, it is unknown whether polyploidization in this model has an impact on the development of steatosis and the progression towards liver cancer. Here, we used a liver-specific conditional knockout approach to delete Pten in combination with deletion of E2f7/8, known key inducers of polyploidization. As expected, Pten deletion caused severe steatosis and liver tumours accompanied by enhanced polyploidization. Additional deletion of E2f7/8 inhibited polyploidization, alleviated Pten-induced steatosis without affecting lipid species composition and accelerated liver tumour progression. Global transcriptomic analysis showed that inhibition of polyploidization in Pten-deficient livers resulted in reduced expression of genes involved in energy metabolism, including PPAR-gamma signalling. However, we find no evidence that deregulated genes in Pten-deficient livers are direct transcriptional targets of E2F7/8, supporting that reduction in steatosis and progression towards liver cancer are likely consequences of inhibiting polyploidization. Lastly, flow cytometry and image analysis on isolated primary wildtype mouse hepatocytes provided further support that polyploid cells can accumulate more lipid droplets than diploid hepatocytes. Collectively, we show that polyploidization promotes steatosis and function as an important barrier against liver tumour progression in Pten-deficient livers.

265P Phase II study of DHP107 oral paclitaxel compared to IV paclitaxel in patients with HER2-negative recurrent or metastatic breast cancer (MBC): Opera (NCT03326102)

Paclitaxel is an antimitotic agent with demonstrated antineoplastic effect in various cancers including breast cancer. DHP107 (Liporaxel®) is an oral paclitaxel based on a novel lipid formulation approved in Korea for gastric cancer in 2016. This phase II randomized trial aimed to evaluate the efficacy and safety of DHP107 compared with IV paclitaxel (ptx).

Enhanced potato tuber penetration of carboxin via ultradeformable liposomes

For the first time, a nanoformulated fungicide carboxin was obtained to solve the problem of infection of potato tubers with fungi spores. Encapsulation of carboxin in ultra-deformable liposomes protects it from degradation by sunlight, increases solubility in water and penetration through potato skin. Two fluorescent probes, rhodamine B and fluorescein, were used for optimization of original composition and for visualization of the transfersome localization in potato tubers, respectively. Carboxin was encapsulated in lipid formulations with further evaluation of encapsulation efficiency, substrate release rate in vitro, and penetration through the Strat-M® membrane using Franz cells. Using fluorescent microscopy, it was revealed that transfersomes penetrate through the periderm and enter cortex of potato tubers. By the extraction it was shown that potato tubers weighing 100 g included 32 mg of carboxin after the transfersome treatment. The inclusion of carboxin in transfersomes made it possible to increase the maximum concentration of carboxin in water from 0.57 mmol L−1 to 2.8–3.8 mmol L−1, i.e., 5–7 times.

Self-Emulsifying Drug Delivery Systems (SEDDS): Measuring Energy Dynamics to Determine Thermodynamic and Kinetic Stability.

This research was designed to identify thermodynamically and kinetically stable lipidic self-emulsifying formulations through simple energy dynamics in addition to highlighting and clarifying common ambiguities in the literature in this regard. Proposing a model study, this research shows how most of the professed energetically stable systems are actually energetically unstable, subjected to indiscriminate and false characterization, leading to significant effects for their pharmaceutical applications. A self-emulsifying drug delivery system (SEDDS) was developed and then solidified (S-SEDDS) using a model drug finasteride. Physical nature of SEDDS was identified by measuring simple dynamics which showed that the developed dispersion was thermodynamically unstable. An in vivo study of albino rats showed a three-fold enhanced bioavailability of model drug with SEDDS as compared to the commercial tablets. The study concluded that measuring simple energy dynamics through inherent properties can distinguish between thermodynamically stable and unstable lipidic systems. It might lead to correct identification of a specific lipidic formulation and the application of appropriate characterization techniques accordingly. Future research strategies include improving their pharmaceutical applications and understanding the basic differences in their natures.

Will the Drugs of the Future Be Small Molecules or Biological Drugs?

After the approval of the first therapeutic monoclonal antibodies and their successful introduction into therapy, a great future was expected for this class of drugs. This assumption has been fulfilled to a limited extent only, especially in the treatment of oncological problems, some autoimmune diseases and in the treatment of some rare diseases. On the other hand, a considerable progress has been made in the fields of oncology and autoimmune diseases by discovering protein kinases, and these small molecule drugs represent alternatives in the treatment of a range of such diseases. In this article, we have tried to shed light mainly on the role of small molecules in therapy, including problems connected with the development of this class of drugs. For many of them, their physico-chemical properties prevent using traditional formulation techniques and modern technologies must be applied. This paper summarizes the most commonly used approaches for increasing bioavailability, including both the prodrug approach and the use of various solid forms of the active ingredient in specific formulations available on the market. The article also provides examples of practical use of amorphous solid dispersions and modern trends, including the development of various types of lipid formulations.

Bioassay-Guided extraction of andrographis paniculata for intervention of in-vitro prostate cancer progression in metabolic syndrome environment.

Metabolic syndrome (MetS) is a risk factor for prostate cancer (PCa) progression. Thus, this life-threatening disease demands a proactive treatment strategy. Andrographis paniculata (AP) is a promising candidate with various medicinal properties. However, the bioactivity of AP is influenced by its processing conditions especially the extraction solvent. In the present study, bioassay-guided screening technique was employed to identify the best AP extract in the management of MetS, PCa, and MetS-PCa co-disease in vitro. Five AP extracts by different solvent systems; APE1 (aqueous), APE2 (absolute methanol), APE3 (absolute ethanol), APE4 (40% methanol), and APE5 (60% ethanol) were screened through their phytochemical profile, in-vitro anti-cancer, anti-obese, and anti-hyperglycemic properties. The best extract was further tested for its potential in MetS-induced PCa progression. APE2 contained the highest andrographolide (1.34 ± 0.05mg/mL) and total phenolic content (8.85 ± 0.63 GAE/gDW). However, APE3 has the highest flavonoid content (11.52 ± 0.80 RE/gDW). APE2 was also a good scavenger of DPPH radicals (EC50 = 397.0µg/mL). In cell-based assays, among all extracts, APE2 exhibited the highest antiproliferative activity (IC50 = 57.5 ± 11.8µg/mL) on DU145 cancer cell line as well as on its migration activity. In in-vitro anti-obese study, all extracts significantly reduced lipid formation in 3T3-L1 cells. The highest insulin-sensitizing and -mimicking actions were exerted by both APE2 and APE3. Taken together, APE2 showed collectively good activity in the inhibition of PCa progression and MetS manifestation in vitro, compared to other extracts. Therefore, APE2 was further investigated for its potential to intervene DU145 progression induced with leptin (10-100ng/mL) and adipocyte conditioned media (CM) (10% v/v). Interestingly, APE2 significantly diminished the progression of the cancer cell that has been pre-treated with leptin and CM through cell cycle arrest at S phase and induction of cell death. In conclusion, AP extracts rich with andrographolide has the potential to be used as an alternative to ameliorate PCa progression induced by factors highly expressed in MetS.

Effect of Lactobacillus plantarum LP104 on hyperlipidemia in high-fat diet induced C57BL/6N mice via alteration of intestinal microbiota

• L. plantarum LP104 alleviates dyslipidemia and chronic inflammation in HFD-induced hyperlipidemic mice. • L. plantarum LP104 ameliorates dyslipidemia by regulaing the gut microbiota. • L. plantarum LP104 inhibits lipid formation and promotes lipolysis in HFD-induced mice through SREBP-1/PPARα signaling pathway. • L. plantarum LP104 provides an idea for the development of natural hypolipidemic foods. The beneficial effects of Lactobacillus plantarum LP104 was investigated on lipid level and the disordered gut microbiota of HFD feeding C57BL/6N mice. C57BL/6N mice were divided into three groups, ordinary diet (Control), high-fat diet (HFD) and HFD with LP104, respectively. After 8 weeks, LP104 alleviated the body weight, liver index, colon length, TC, TG, LDL, TNFα and LPS levels. High-throughput sequencing analysis has found that long-term HFD destroy microbial abundance and composition in the gut. Nevertheless, dietary supplementation of LP104 reduced the ratio of Firmicutes to Bacteroides and regulate the gut microbiota community structure positively. Meanwhile, the intake of LP104 also increased the abundance of beneficial bacteria Bifidobacterium in the cecum, which improves the intestinal flora disorder induced by a high-fat diet. The present study shows that LP104 supplementation improved the amelioration HFD induced hyperlipidemia by positively regulating intestinal microorganisms.

Fructus Zanthoxyli extract improves glycolipid metabolism disorder of type 2 diabetes mellitus via activation of AMPK/PI3K/Akt pathway: Network pharmacology and experimental validation

ObjectiveThis study investigated the potential mechanisms behind the beneficial effects of Fructus Zanthoxyli (FZ) against type 2 diabetes mellitus (T2DM) based on network pharmacology and experimental validation. MethodsUltra-high-performance liquid chromatography coupled with hybrid quadrupole-orbitrap high-resolution mass spectrometry, and gas chromatography-mass spectrometry were used to identify the constituents of FZ. Next, the differentially expressed genes linked to the treatment of diabetes with FZ were screened using online databases (including Gene Expression Omnibus database and Swiss Target Prediction online database), and the overlapping genes and their enrichment were analyzed by Kyoto Encyclopedia of Genes and Genomes (KEGG). Finally, the pathway was verified by in vitro experiments, and cell staining with oil red and Nile red showed that the extract of FZ had a therapeutic effect on T2DM. ResultsA total of 43 components were identified from FZ, and 39 differentially expressed overlapping genes were screened as the possible targets of FZ in T2DM. The dug component-target network indicated that PPARA, PPARG, PIK3R3, JAK2 and GPR88 might be the core genes targeted by FZ in the treatment of T2DM. Interestingly, the enrichment analysis of KEGG showed that effects of FZ against T2DM were closely correlated with the adenosine monophosphate-activated protein kinase (AMPK) and phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) signaling pathways. In vitro experiments further confirmed that FZ significantly inhibited palmitic acid-induced lipid formation in HepG2 cells. Moreover, FZ treatment was able to promote the AMPK and PI3K/Akt expressions in HepG2 cells. ConclusionNetwork pharmacology combined with experimental validation revealed that FZ extract can improve the glycolipid metabolism disorder of T2DM via activation of the AMPK/PI3K/Akt pathway.

Effects of frozen temperature and multiple freeze–thaw cycles on gel structure, protein and lipid oxidation and formation of advanced glycation end‐products in unwashed silver carp surimi

SummaryThe effects of frozen temperature (−18 or −60 °C) and multiple freeze–thaw (FT) cycles on the gel structure, protein denaturation and oxidation, lipid oxidation and formation of protein‐bound Nε‐carboxymethyllysine (CML) and Nε‐carboxyethyllysine (CEL) in unwashed silver carp surimi were investigated. The levels of CML and CEL in raw and heat‐treated surimi increased due to multiple FT treatment, which were positively correlated with the thiobarbituric acid‐reactive substances (TBARS) and protein carbonyl content that also increased during FT cycles, and negatively correlated with the total sulfhydryl content and Ca2+‐ATPase activity that decreased during FT cycles. Besides, the gel structure of unwashed surimi was improved by 3 FT cycles and frozen at −60 °C, which was significantly helpful to inhibit the formation of protein carbonyl and CEL in raw surimi, but showed no significant influence on the TBARS and CML levels as compared to that at −18 °C.

REVIEW ON: EFFECT OF OIL, SURFACTANT AND COSURFACTANT ON MICROEMULSION

Lipid dosage forms are the most preferred delivery system for hydrophobic drug molecules. Lipid dosage forms has many advantages of higher degree of biocompatibility and versatility and also lipid dosage form gained more importance in recent years because of their ability to improve the solubility and bioavailability of drugs with poor water solubility. Lipid formulation can be altered in various ways to provide wide range of product requirements as per the disease condition, route of administration, toxicity and efficacy. Lipid formulations are most reliable strategy for formulating pharmaceuticals, for topical, oral, pulmonary, or parenteral delivery. Due to their capability as therapeutic agents, ideally, these lipid-soluble drugs are incorporated into inert lipid carriers such as oil, surfactant dispersion, liposomes, emulsion etc. Emulsion is one of the known systems since many years. Pharmaceutical application of the emulsion is widely speeded after the microemulsion and nano emulsions appearance. Microemulsions are clear, stable and isotropic mixture of oil, surfactant and cosurfactant. Emulsions and nano emulsions are not thermodynamically stable, compared with microemulsions. The main objective of this review paper is to discuss about the effect of oil, surfactant and cosurfactant on the microemulsions.

The Role of Human Milk Lipids and Lipid Metabolites in Protecting the Infant against Non-Communicable Disease.

Non-communicable diseases continue to increase globally and have their origins early in life. Early life obesity tracks from childhood to adulthood, is associated with obesity, inflammation, and metabolic dysfunction, and predicts non-communicable disease risk in later life. There is mounting evidence that these factors are more prevalent in infants who are formula-fed compared to those who are breastfed. Human milk provides the infant with a complex formulation of lipids, many of which are not present in infant formula, or are present in markedly different concentrations, and the plasma lipidome of breastfed infants differs significantly from that of formula-fed infants. With this knowledge, and the knowledge that lipids have critical implications in human health, the lipid composition of human milk is a promising approach to understanding how breastfeeding protects against obesity, inflammation, and subsequent cardiovascular disease risk. Here we review bioactive human milk lipids and lipid metabolites that may play a protective role against obesity and inflammation in later life. We identify key knowledge gaps and highlight priorities for future research.

Design and Functional Characterization of HIV-1 Envelope Protein-Coupled T Helper Liposomes.

Functionalization of experimental HIV-1 virus-like particle vaccines with heterologous T helper epitopes (T helper VLPs) can modulate the humoral immune response via intrastructural help (ISH). Current advances in the conjugation of native-like HIV-1 envelope trimers (Env) onto liposomes and encapsulation of peptide epitopes into these nanoparticles renders this GMP-scalable liposomal platform a feasible alternative to VLP-based vaccines. In this study, we designed and analyzed customizable Env-conjugated T helper liposomes. First, we passively encapsulated T helper peptides into a well-characterized liposome formulation displaying a dense array of Env trimers on the surface. We confirmed the closed pre-fusion state of the coupled Env trimers by immunogold staining with conformation-specific antibodies. These peptide-loaded Env-liposome conjugates efficiently activated Env-specific B cells, which further induced proliferation of CD4+ T cells by presentation of liposome-derived peptides on MHC-II molecules. The peptide encapsulation process was then quantitatively improved by an electrostatically driven approach using an overall anionic lipid formulation. We demonstrated that peptides delivered by liposomes were presented by DCs in secondary lymphoid organs after intramuscular immunization of mice. UFO (uncleaved prefusion optimized) Env trimers were covalently coupled to peptide-loaded anionic liposomes by His-tag/NTA(Ni) interactions and EDC/Sulfo-NHS crosslinking. EM imaging revealed a moderately dense array of well-folded Env trimers on the liposomal surface. The conformation was verified by liposomal surface FACS. Furthermore, anionic Env-coupled T helper liposomes effectively induced Env-specific B cell activation and proliferation in a comparable range to T helper VLPs. Taken together, we demonstrated that T helper VLPs can be substituted with customizable and GMP-scalable liposomal nanoparticles as a perspective for future preclinical and clinical HIV vaccine applications. The functional nanoparticle characterization assays shown in this study can be applied to other systems of synthetic nanoparticles delivering antigens derived from various pathogens.

Preclinical development of sodium fusidate antibiotic cutaneous spray based on water-free lipid formulation system

Topical antibiotics are a key component in the management of mild to moderate skin and soft tissue infections. There are, however, concerns about the emerging bacterial resistance against topical antibacterial agents such as fusidic acid, due to the prolonged treatment period of its marketed dosage forms. Improving the efficacy of topical formulations could potentially shorten the treatment period and avoid the resistance growth. To provide a more effective drug delivery, a water-free lipid-based formulation system (AKVANO®) which can be applied by spraying, has been developed. In the current paper, different formulations containing sodium fusidate were evaluated for their in vitro skin permeability using artificial skin mimicking membranes and antibacterial properties using ex vivo and in vivo skin wound infection models. The novel formulations containing sodium fusidate showed a much higher skin permeation (up to 60% of nominal amount) than the commercially available Fucidin® cream (3%). These formulations also gave a significantly stronger antibacterial effect than Fucidin cream showing a clear dose-response relationship for the sodium fusidate content. A spray product based on the described formulation technology would therefore require a shorter treatment time and thereby lower the risk for the development of bacterial resistance. Spray administration of these formulations provides an even layer on the skin surface from which the solvent quickly evaporates and thereby facilitates a non-touch application where no rubbing is required.

Acetylcholinesterase and butyrylcholinesterase inhibitory activities of antioxidant peptides obtained from enzymatic pea protein hydrolysates and their ultrafiltration peptide fractions.

This study optimized the enzymatic hydrolysis of yellow field pea proteins using alcalase (ACH), chymotrypsin (CHH), flavourzyme (FZH), pancreatin (PCH), pepsin (PEH), and trypsin (TPH) to obtain hydrolysates and ultrafiltered fractions (<1, 1-3, 3-5 and 5-10kDa) that possess antioxidant plus acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory activities. The hydrolysates exhibited varying degrees of radical scavenging and inhibition of linoleic acid peroxidation, as well as cholinesterase inhibition activities but the potency generally improved by >10% after UF separation into peptide fractions. ACH, FZH, and PEH exhibited significantly (p< .05) higher (20%-30% increases) radical scavenging activities than the other hydrolysates. The 1 and 3kDa UF fractions of ACH, FZH, and PEH inhibited ~20%-30% AChE activity, while ACH, PCH, TPH, and PEH inhibited ~20%-40% BuChE activity. We conclude that the pea protein hydrolysates and their peptide fractions possess multifunctional properties with potential use against neurodegenerative disorders. PRACTICAL APPLICATIONS: Alzheimer's disease (AD) has multiple pathological pathways in addition to the loss of acetylcholine (ACh) catalyzed by acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). The presence of severe oxidative stress triggered by lipid peroxidation and formation of free radicals is a common trait in AD patients. The concept of AChE and BuChE inhibition as an approach toward AD amelioration involves the use of compounds with a similar structure to ACh, the natural substrate. Peptides derived from food proteins consist of ester bonds with structural similarity to ACh and theoretically possess the ability to interact with AChE and BuChE. Results from the present study imply that pea protein-derived peptides are potential candidates for use as inhibitors of AChE and BuChE activities, with application in the prevention and management of AD.

Controlling drug release by introducing lipase inhibitor within a lipid formulation

Drug overdose connected to marketed pharmaceutical products, particularly opioids, occurs at an alarming rate. Novel strategies through innovative formulation approaches that reduce the likelihood of overdose while allowing safe therapeutic outcomes are urgently required. The current study provides a proof-of-concept for a new formulation approach by co-formulating drug with a lipase inhibitor within a solid lipid formulation in order to prevent or reduce the harmful effects of taking multiple doses of an oral solid dose form. Lipase inhibitor controlled-release (LICR) formulations were created using a simple hot melt method to co-formulate the inhibitor (orlistat) and ibuprofen, as the model drug, within the lipid matrix. The digestion and drug release kinetics were determined using an in vitro lipolysis model. Above a threshold level of orlistat there was decreased digestibility of multiple doses of the LICR formulations, leading to reduced drug release. Upon administration of the formulations in capsules to rats, the LICR formulation displayed the lowest exposure of ibuprofen during the pharmacokinetic studies. This novel formulation approach shows promise in preventing accidental drug overdose after oral administration of multiple doses of formulation.