Engineering butylglyceryl-modified polysaccharides towards nanomedicines for brain drug delivery

Colloidal systems prepared from carbohydrates are subject of intense research due to their potential to enhance drug permeability through biological membranes, however their characteristics and performance are never compared directly. Here we report the results of a comparative investigation of a series of butylglyceryl-modified polysaccharides (chitosan, guar gum, and pullulan) that were formulated into nanoparticles and loaded with a range of model actives (Doxorubicin, Rhodamine B, Angiotensin II). Butylglyceryl-modified guar gum and corresponding pullulan nanocarriers were more stable at physiological pH compared to those obtained from modified chitosan, and studies of the in-vitro interactions with mouse brain endothelial cells (bEnd3) indicated an increased biological membrane permeability and lack of toxicity at application-relevant concentrations. No significant haemolytic effect was observed, and confocal microscopy and flow cytometry studies confirmed the efficient cellular uptake and cytoplasmic localisation of NPs. Most promising characteristics for brain drug delivery applications were demonstrated by butylglyceryl pullulan nanocarriers

Butylglyceryl pectin nanoparticles: synthesis, formulation and characterization

Pectin is a polysaccharide with very good gel forming properties that traditionally has found important applications in foods and pharmaceutical industries. Although less studied, chemical modifications of pectin leading to a decrease in its hydrophilicity can be useful for the development of novel drug carriers. To this aim, butylglyceryl pectins (P-OX4) were synthesized via functionalization with n-butylglycidyl ether and subsequently formed into nanoparticles. Chromatographic, spectroscopic, and thermal analytical methods were employed to characterize the novel butylglyceryl pectins (P-OX4) obtained, prior to their formulation into nanoparticles via nanoprecipitation. Nuclear magnetic resonance (NMR) and Fourier transform infrared (FT-IR) spectroscopy confirmed a degree of modification in these materials in the range 10.4−13.6%, and thermal stability studies indicated an increase in both the thermal decomposition onset and glass transition temperature values (compared to those of the original pectin). An increase in the molecular weight and a decrease in the viscosity of P-OX4, when compared to the starting material, were also observed. The resulting nanoformulations were investigated in terms of particle morphology, size and stability, and it was found that particles were roughly spherical, with their size below 300 nm, and a negative zeta potential (−20 to −26 mV, indicating good stability). Having demonstrated the ability to load Doxorubicin at the level of 10%, their potential in drug delivery applications warrants further investigations

Butylglyceryl Pectin Nanoparticles: Synthesis, Formulation and Characterization

Pectin is a polysaccharide with very good gel forming properties that traditionally has found important applications in foods and pharmaceutical industries. Although less studied, chemical modifications of pectin leading to a decrease in its hydrophilicity can be useful for the development of novel drug carriers. To this aim, butylglyceryl pectins (P-OX4) were synthesized via functionalization with n-butylglycidyl ether and subsequently formed into nanoparticles. Chromatographic, spectroscopic, and thermal analytical methods were employed to characterize the novel butylglyceryl pectins (P-OX4) obtained, prior to their formulation into nanoparticles via nanoprecipitation. Nuclear magnetic resonance (NMR) and Fourier transform infrared (FT-IR) spectroscopy confirmed a degree of modification in these materials in the range 10.4–13.6%, and thermal stability studies indicated an increase in both the thermal decomposition onset and glass transition temperature values (compared to those of the original pectin). An increase in the molecular weight and a decrease in the viscosity of P-OX4, when compared to the starting material, were also observed. The resulting nanoformulations were investigated in terms of particle morphology, size and stability, and it was found that particles were roughly spherical, with their size below 300 nm, and a negative zeta potential (−20 to −26 mV, indicating good stability). Having demonstrated the ability to load Doxorubicin at the level of 10%, their potential in drug delivery applications warrants further investigations

Amphiphilic Alkylated Pectin Hydrogels for Enhanced Topical Delivery of Fusidic Acid: Formulation and In Vitro Investigation

Hydrogels constructed of amphiphilically modified polysaccharides have attracted a lot of interest because of their potential to augment drug diffusion over the skin. This research describes the synthesis of amphiphilic alkylated pectin via glycidyl tert-butyl ether modification (alkylation degree 15.7%), which was characterized using spectroscopic and thermal analysis techniques and then formulated into hydrogels for the study of their potential in regulating fusidic acid diffusion topically. The hydrogels were formulated by the ionic interaction of negatively charged pectin and positively charged crosslinker CaCl2, with a reported fusidic acid loading degree of 93–95%. Hydrogels made of alkylated pectin showed a lower swelling percentage than that of native pectin, resulting in a slower fusidic acid release. The influence of pH on the swelling percentage and drug release was also investigated, with results revealing that greater pH enhanced swelling percentage and drug release. The in vitro interactions with HaCaT cells revealed negligible cytotoxicity under application-relevant settings. Utilizing Franz diffusion cells, the alkylated pectin hydrogels caused fusidic acid to penetrate the Strat-M® membrane at a 1.5-fold higher rate than the native pectin hydrogels. Overall, the in vitro results showed that alkylated pectin hydrogels have a lot of promise for topical distribution, which needs further investigation

Hydrophobically Grafted Pullulan Nanocarriers for Percutaneous Delivery: Preparation and Preliminary In Vitro Characterisation

Polymeric colloidal nanocarriers formulated from hydrophobically grafted carbohydrates have been the subject of intensive research due to their potential to increase the percutaneous penetration of hydrophilic actives. To this goal, a series of hydrophobically grafted pullulan (BMO-PUL) derivatives with varying degree of grafting (5–64%) was prepared through functionalisation with 2-(butoxymethyl)oxirane. The results demonstrated that monodispersed BMO-PUL nanocarriers (size range 125–185 nm) could be easily prepared via nanoprecipitation; they exhibit close-to-spherical morphology and adequate stability at physiologically relevant pH. The critical micellar concentration of BMO-PUL was found to be inversely proportional to their molecular weight (Mw) and degree of grafting (DG), with values of 60 mg/L and 40 mg/L for DG of 12.6% and 33.8%, respectively. The polymeric nanocarriers were loaded with the low Mw hydrophilic active α-arbutin (16% loading), and the release of this active was studied at varying pH values (5 and 7), with a slightly faster release observed in acidic conditions; the release profiles can be best described by a first-order kinetic model. In vitro investigations of BMO-PUL nanocarriers (concentration range 0.1–4 mg/mL) using immortalised skin human keratinocytes cells (HaCaT) evidenced their lack of toxicity, with more than 85% cell viability after 24 h. A four-fold enhance in arbutin permeation through HaCaT monolayers was recorded when the active was encapsulated within the BMO-PUL nanocarriers. Altogether, the results obtained from the in vitro studies highlighted the potential of BMO-PUL nanocarriers for percutaneous delivery applications, which would warrant further investigation in vivo

Depression, anxiety, and stress among university students in Selangor, Malaysia during COVID-19 pandemics and their associated factors.

IntroductionThis study aims to assess the impacts of COVID-19 pandemics among university students in Malaysia, by identifying the prevalence of depression, anxiety and stress among them and their respective predictors.MethodologyAn online cross-sectional study was conducted via non-probabilistic convenience sampling. Data were collected on sociodemographic characteristics, lifestyle, COVID-19 related influences. Mental health status was assessed with depression, anxiety, and stress scale (DASS-21).Results388 students participated this study (72.4% female; 81.7% Bachelor's student). The prevalence of moderate to severe depression, anxiety and stress among university students are 53.9%, 66.2% and 44.6%, respectively. Multivariable logistic regression analysis found that the odds of depression were lower among students who exercise at least 3 times per week (OR: 0.380, 95% CI: 0.203-0.711). The odd ratio of student who had no personal history of depression to had depression, anxiety and stress during this pandemic was also lower in comparison (OR: 0.489, 95% CI: 0.249-0.962; OR: 0.482, 95% CI: 0.241-0.963; OR: 0.252, 95% CI: 0.111-0.576). Surprisingly, students whose are currently pursuing Master study was associated with lower stress levels (OR: 0.188, 95% CI: 0.053-0.663). However, student who had poorer satisfaction of current learning experience were more likely to experience stress (OR: 1.644, 95% CI: 1.010-2.675).LimitationsIt is impossible to establish causal relationships between variables on mental health outcomes, and there is a risk of information bias.ConclusionThe prevalence of mental health issues among university students is high. These findings present essential pieces of predictive information when promoting related awareness among them

Papain-Decorated Mucopenetrating SEDDS: A Tentative Approach to Combat Absorption Issues of Acyclovir via the Oral Route

The aim of the current study was to enhance the oral bioavailability of Acyclovir (ACV) based on the papain-functionalized self-emulsifying drug delivery systems (SEDDS). The optimum control SEDDS formulation comprised of kolliphore (40%), transcutol (30%), propylene glycol (20%) and oleoyl chloride (10%). However, in the targeted SEDDS formulation, oleoyl chloride was replaced with oleoyl chloride-papain (OC-PAP) conjugate that was synthesized via an amide bond formation between the acyl halide groups of oleoyl chloride and the amino group of papain. Prior to adding in the SEDDS formulation, the newly synthesized conjugate was evaluated quantitatively by a Bradford assay that demonstrated 45 µg of papain contents per mg of the conjugate. Moreover, the conjugate formation was qualitatively confirmed through FTIR analysis and thin layer chromatography. ACV (a BCS class III drug) was incorporated into the SEDDS formulations after being hydrophobically ion paired with sodium deoxycholate, thereby making it lipophilic. The drug-loaded formulations were emulsified in the 0.1 M phosphate buffer (pH 6.8) and evaluated in vitro with respect to drug release and rabbit mucosal permeation studies. Both the formulations illustrated a very comparable drug release over a period of 4 h, afterwards, the OC-PAP-based formulation demonstrated a more sustaining effect. The extent of mucus diffusion evaluated via the silicon tube method demonstrated a 4.92-fold and a 1.46-fold higher penetration of the drug, a 3.21-fold and a 1.56-fold higher permeation through the rabbit intestinal mucus layer, and a 22.94-fold and a 2.27-fold higher retention of the drug over the intact mucosa of rabbit intestine, illustrated by OC-PAP-based nanoemulsions compared to the drug-free solution and controlled nanoemulsion, respectively. According to these in vitro results, papain-functionalized SEDDS is a promising approach for the oral delivery of ACV and many other drugs with oral bioavailability issues, however, in vivo studies in this respect have to be employed before making a comprehensive conclusion

Investigations of amphiphilic butylglyceryl-functionalized dextran nanoparticles for topical delivery

Toward the development of colloidal systems that can enhance transdermal permeation of hydrophilic actives, a material combining the non‐toxic of dextran with alkylglycerols permeation enhancing property has been designed. To this purpose, a range of amphiphilic butylglyceryl dextrans (DEX‐OX4) was synthesized via modification with n‐butylglycidyl ether with a degree of functionalization in the range 6.3%–35.7%. A reduced viscosity and an increased molecular weight of DEX‐OX4 were recorded when compared to the starting material. DEX‐OX4 was formulated into nanocarriers and loaded with α‐arbutin prior to characterization—the nanoparticles (180–220 nm size) were found to be close‐to‐spherical, stable at pH 5 and 7, with a loading capacity of 11.7%. Slower release of α‐arbutin from the nanoparticles was demonstrated when tested in acidic media. Lack of toxicity at application‐relevant concentrations and increased permeation were demonstrated by nanoparticles in vitro results against immortalized skin human keratinocytes cells (HaCaT)

Biomimetic cell membrane‐coated poly(lactic‐co‐glycolic acid) nanoparticles for biomedical applications

Abstract Poly(lactic‐co‐glycolic acid) (PLGA) nanoparticles (NPs) are commonly used for drug delivery because of their favored biocompatibility and suitability for sustained and controlled drug release. To prolong NP circulation time, enable target‐specific drug delivery and overcome physiological barriers, NPs camouflaged in cell membranes have been developed and evaluated to improve drug delivery. Here, we discuss recent advances in cell membrane‐coated PLGA NPs, their preparation methods, and their application to cancer therapy, management of inflammation, treatment of cardiovascular disease and control of infection. We address the current challenges and highlight future research directions needed for effective use of cell membrane‐camouflaged NPs

Biomimetic cell membrane-coated poly(lactic-co-glycolic acid) nanoparticles for biomedical applications

Poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) are commonly used for drug delivery because of their favored biocompatibility and suitability for sustained and controlled drug release. To prolong NP circulation time, enable target-specific drug delivery and overcome physiological barriers, NPs camouflaged in cell membranes have been developed and evaluated to improve drug delivery. Here, we discuss recent advances in cell membrane-coated PLGA NPs, their preparation methods, and their application to cancer therapy, management of inflammation, treatment of cardiovascular disease and control of infection. We address the current challenges and highlight future research directions needed for effective use of cell membrane-camouflaged NPs