Emerging materials and technologies for advancing bioresorbable surgical meshes.

Surgical meshes play a significant role in the treatment of various medical conditions, such as hernias, pelvic floor issues, guided bone regeneration, and wound healing. To date, commercial surgical meshes are typically made of non-absorbable synthetic polymers, notably polypropylene and polytetrafluoroethylene, which are associated with postoperative complications, such as infections. Biological meshes, based on native tissues, have been employed to overcome such complications, though mechanical strength has been a main disadvantage. The right balance in mechanical and biological performances has been achieved by the advent of bioresorbable meshes. Despite improvements, recurrence of clinical complications associated with surgical meshes raises significant concerns regarding the technical adequacy of current materials and designs, pointing to a crucial need for further development. To this end, current research focuses on the design of meshes capable of biomimicking native tissue and facilitating the healing process without post-operative complications. Researchers are actively investigating advanced bioresorbable materials, both synthetic polymers and natural biopolymers, while also exploring the performance of therapeutic agents, surface modification methods and advanced manufacturing technologies such as 4D printing. This review seeks to evaluate emerging biomaterials and technologies for enhancing the performance and clinical applicability of the next-generation surgical meshes. STATEMENT OF SIGNIFICANCE: In the ever-transforming landscape of regenerative medicine, the embracing of engineered bioabsorbable surgical meshes stands as a key milestone in addressing persistent challenges and complications associated with existing treatments. The urgency to move beyond conventional non-absorbable meshes, fraught with post-surgery complications, emphasises the necessity of using advanced biomaterials for engineered tissue regeneration. This review critically examines the growing field of absorbable surgical meshes, considering their potential to transform clinical practice. By strategically combining mechanical strength with bioresorbable characteristics, these innovative meshes hold the promise of mitigating complications and improving patient outcomes across diverse medical applications. As we navigate the complexities of modern medicine, this exploration of engineered absorbable meshes emerges as a promising approach, offering an overall perspective on biomaterials, technologies, and strategies adopted to redefine the future of surgical meshes.

Matrix hyaluronic acid and bilayer poly-hydroxyethyl methacrylate-hyaluronic acid films as potential ocular drug delivery platforms.

This study aimed to design hydrogel based films comprising hyaluronic acid (HA) to overcome limitations of currently used eye drops. Timolol-loaded crosslinked (X2) HA-based and bilayer (B2) (pHEMA/PVP-HA-based layers) films were designed and characterized. The films were transparent (UV, visual observation) with crosslinked (<80 %) films showing lower light transmittance than bilayer (>80 %) films. X2 showed significantly higher swelling capacity, tensile strength and elastic modulus (5491.6 %, 1539.8 Nmm-2, 1777.2 mPa) than B2 (1905.0 %, 170.0N mm-2, 67.3 mPa) respectively. However, X2 showed lower cumulative drug released and adhesive force (27.3 %, 6.2 N) than B2 (57.5 %, 8.6 N). UV sterilization did not significantly alter physical properties, while SEM and IR microscopy showed smooth surface morphology and homogeneous drug distribution. Timolol permeation (EpiCorneal™/porcine cornea) depended on the film matrix with erodible films showing similar permeation to commercial eyedrops. Drug permeation for porcine cornea (X2 = 549.0.2, B2 = 312.1 µgcm-2 h-1) was significantly faster than EpiCorneal™ (X2 = 55.2, B2 = 37.6 µgcm-2 h-1), but with a linear correlation between them. All the selected optimized films showed acceptable compatibility (MTT assay) with both HeLa cells and EpiCorneal™. In conclusion, crosslinked and bilayer HA based films showed ideal characteristics suitable for potential ocular drug delivery, though further work is required to further optimize these properties and confirm their efficacy including in vivo tests.

Surface functionalization of PLGA nanoparticles for potential oral vaccine delivery targeting intestinal immune cells.

This study aimed to develop surface modified PLGA nanocarriers protecting a protein-based antigen in the stomach to enable potential release of the antigen at target intestinal sites. PLGA nanoparticles (NPs) were prepared by double emulsion and solvent evaporation techniques while surface functionalization was performed using polyethylene glycol (PEG), sodium alginate (ALG) and Eudragit L100 (EUD) with ovalbumin (OVA) as a model protein antigen. Nanoparticles were characterized by dynamic light scattering (DLS), scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), gel permeation chromatography (GPC), and stability in simulated gastric fluid (SGF)/simulated intestinal fluid (SIF). Structural integrity of released OVA was analyzed by circular dichroism (CD) and sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), while cytotoxicity against Jurkat cells was determined using MTT assay. Surface functionalized PLGA NPs protected the protein in SGF and SIF better than the non-functionalized NPs. Average size of OVA encapsulated NPs was between 235 and 326 nm and were spherical. FTIR band change was observed after surface modification and the surface modified NPs showed sustained OVA release compared with the uncoated NPs. The secondary structure of OVA released after 96 h remained intact and MTT assay showed >80 % cell viability after 72 h while unmodified and surface modified NPs achieved 17 % and 48 % mucin binding respectively. In conclusion, surface modified PLGA NPs have been shown to be safe for potential oral protein-based vaccine delivery.

Novel Mucoadhesive Wafers for Treating Local Vaginal Infections.

Current vaginal formulations, such as gels and pessaries, have limitations, including poor retention. Therefore, the use of mucoadhesive formulations that adhere to the vaginal wall would allow prolonged retention and controlled drug release while reducing the required dose and the potential toxicity associated with high drug loading. The aim of the current research was to develop, characterize, and optimize freeze-dried wafers loaded with metronidazole (MTz) to treat vaginal bacterial infections. Blank (BLK) composite wafers comprising carrageenan (CARR) and sodium alginate (SA) were initially formulated; however, due to poor physico-chemical properties, Carbopol (CARB), hydroxypropylmethylcellulose (HPMC), and polyethylene glycol 200 (PEG) were included. The MTz-loaded formulations were obtained by loading optimized composite CARB:CARR- or CARB:SA-based gels (modified with HPMC and/or PEG) with 0.75% of MTz prior to freeze-drying. The physico-chemical properties were investigated using texture analysis (resistance to compressive deformation and adhesion), scanning electron microscopy (SEM), X-ray diffractometry (XRD), and attenuated total reflectance Fourier-transform infrared (ATR-FTIR) spectroscopy. Functional properties were investigated by examining the swelling, porosity, drug release, and in vitro antimicrobial activity using E. coli as a model infection-causative agent. The results showed that HPMC and PEG generally improved the wafer's appearance, with smoother surfaces for easy insertion. From the physico-chemical characterization studies, only two composite wafers prepared from 8% CARB:SA 1:4 and 8% CARB:SA 1:9 gels were deemed optimal and loaded with MTz. Both formulations showed sustained drug release and achieved almost 100% cumulative release within 72 h in simulated vaginal fluid. The data obtained from the drug dissolution (release) experiments were fitted to various mathematical equations and showed the highest correlation coefficient with the Higuchi equation, suggesting a drug release based on diffusion from a swollen matrix; this was confirmed by the Korsmeyer-Peppas equation. The released MTz inhibited the growth of the E. coli used as a model bacterial organism.

Studies on Almond Gum and Gelucire-Based Pellets Prepared by Extrusion and Spheronization for Sustained Release.

Objectives: The aim of the investigation was to prepare sustained release (SR) pellets of diltiazem hydrochloride employing almond gum and gelucire. The study was performed to explore the suitability of almond gum in the preparation of pellets of diltiazem hydrochloride without the use of microcrystalline cellulose and role and effectiveness of hydrophobic gelucire (43/01) in controlling the drug release. Materials and Methods: Pellets were prepared by extrusion-spheronization of the blend previously obtained by incorporation of the drug in a mixture of melted gelucire 43/01 and almond gum. A 32 factorial design was employed to study the effect of two independent variables, almond gum and gelucire, on the size, friability and drug release from pellets. Scanning electron microscopy, differential scanning calorimetry and infrared spectroscopy were performed to characterize pellets. Results: Free flowing spherical pellets could be prepared. The 32 factorial study revealed that as the proportion of almond gum increased, the size of pellets increased, while increasing gelucire had opposite effect. The yield of pellets prepared in different formulations is in the range of 86 to 92%. The size of the pellets varied from 1128 to 1458 µ. Higher amounts of gelucire resulted in pellets with greater friability, whereas increasing the amount of almond gum yielded pellets with low friability. The pellets exhibited SR of diltiazem and the presence of gelucire in the matrix of the pellets had an enhanced sustaining effect on release. Conclusion: Dispersion of the drug in gelucire before it was converted to pellets resulted in extended release of drug. The drug release rate changed with changes in the proportion of pellet composition. The results of the study suggest that employing gelucire (43/01) in the preparation of pellets is a useful approach in the design of SR products of highly water-soluble drug such as diltiazem hydrochloride.

Composite Fish Collagen-Hyaluronate Based Lyophilized Scaffolds Modified with Sodium Alginate for Potential Treatment of Chronic Wounds.

Chronic wounds are characterized by both decreased collagen deposition and increased collagen breakdown. It is reasonable to hypothesize that exogenous collagen can potentially promote wound healing by reducing degradation enzymes in the wound environment and disrupting the cycle of chronicity. Therefore, this study aimed to develop an optimal combination of fish collagen (FCOL), sodium alginate (SA), and hyaluronic acid (HA) loaded with bovine serum albumin (BSA) as a model protein fabricated as lyophilized scaffolds. The effects of sodium alginate (SA#) with higher mannuronic acid (M) were compared to sodium alginate (SA*) with higher guluronic acid (G). The SA* with higher G resulted in elegant scaffolds with hardness ranging from 3.74 N−4.29 N that were able to withstand the external force due to the glycosidic bonds in guluronic acid. Furthermore, the high G content also had a significant effect on the pore size, pore shape, and porosity. The water absorption (WA) ranged from 380−1382 (%) and equilibrium water content (EWC) 79−94 (%) after 24 h incubation at 37 °C. The SA* did not affect the water vapor transmission rate (WVTR) but incorporating BSA significantly increased the WVTR making these wound dressing scaffolds capable of absorbing about 50% exudate from a heavily exuding chronic wound. The protein released from the composite systems was best explained by the Korsmeyer−Peppas model with regression R2 values ranging from 0.896 to 0.971 and slope or n < 0.5 indicating that the BSA release mechanism was governed by quasi-Fickian diffusion. Cell viability assay showed that the scaffolds did not inhibit the proliferation of human dermal fibroblasts and human epidermal keratinocytes, and are therefore biocompatible. In vitro blood analysis using human whole blood confirmed that the BSA-loaded SA*:FCOL:HA scaffolds reduced the blood clotting index (BCI) by up to 20% compared to a commercially available sponge for chronic wounds. These features confirm that SA*:FCOL:HA scaffolds could be applied as a multifunctional wound dressing.

The Effects of Enteral Nutrition in Critically Ill Patients with COVID-19: A Systematic Review and Meta-Analysis.

Background: Patients who are critically ill with COVID-19 could have impaired nutrient absorption due to disruption of the normal intestinal mucosa. They are often in a state of high inflammation, increased stress and catabolism as well as a significant increase in energy and protein requirements. Therefore, timely enteral nutrition support and the provision of optimal nutrients are essential in preventing malnutrition in these patients. Aim: This review aims to evaluate the effects of enteral nutrition in critically ill patients with COVID-19. Method: This systematic review and meta-analysis was conducted based on the preferred reporting items for systematic review and meta-Analysis framework and PICO. Searches were conducted in databases, including EMBASE, Health Research databases and Google Scholar. Searches were conducted from database inception until 3 February 2022. The reference lists of articles were also searched for relevant articles. Results: Seven articles were included in the systematic review, and four articles were included in the meta-analysis. Two distinct areas were identified from the results of the systematic review and meta-analysis: the impact of enteral nutrition and gastrointestinal intolerance associated with enteral nutrition. The impact of enteral nutrition was further sub-divided into early enteral nutrition versus delayed enteral nutrition and enteral nutrition versus parenteral nutrition. The results of the meta-analysis of the effects of enteral nutrition in critically ill patients with COVID-19 showed that, overall, enteral nutrition was effective in significantly reducing the risk of mortality in these patients compared with the control with a risk ratio of 0.89 (95% CI, 0.79, 0.99, p = 0.04). Following sub-group analysis, the early enteral nutrition group also showed a significant reduction in the risk of mortality with a risk ratio of 0.89 (95% CI, 0.79, 1.00, p = 0.05). The Relative Risk Reduction (RRR) of mortality in patients with COVID-19 by early enteral nutrition was 11%. There was a significant reduction in the Sequential Organ Failure Assessment (SOFA) score in the early enteral nutrition group compared with the delayed enteral nutrition group. There was no significant difference between enteral nutrition and parenteral nutrition in relation to mortality (RR = 0.87; 95% CI, 0.59, 1.28, p = 0.48). Concerning the length of hospital stay, length of ICU stay and days on mechanical ventilation, while there were reductions in the number of days in the enteral nutrition group compared to the control (delayed enteral nutrition or parenteral nutrition), the differences were not significant (p > 0.05). Conclusion: The results showed that early enteral nutrition significantly (p < 0.05) reduced the risk of mortality among critically ill patients with COVID-19. However, early enteral nutrition or enteral nutrition did not significantly (p > 0.05) reduce the length of hospital stay, length of ICU stay and days on mechanical ventilation compared to delayed enteral nutrition or parenteral nutrition. More studies are needed to examine the effect of early enteral nutrition in patients with COVID-19.

Enhancing Stability and Mucoadhesive Properties of Chitosan Nanoparticles by Surface Modification with Sodium Alginate and Polyethylene Glycol for Potential Oral Mucosa Vaccine Delivery.

Background: The present study aimed to fabricate surface-modified chitosan nanoparticles with two mucoadhesive polymers (sodium alginate and polyethylene glycol) to optimize their protein encapsulation efficiency, improve their mucoadhesion properties, and increase their stability in biological fluids. Method: Ionotropic gelation was employed to formulate chitosan nanoparticles and surface modification was performed at five different concentrations (0.05, 0.1, 0.2, 0.3, 0.4% w/v) of sodium alginate (ALG) and polyethylene glycol (PEG), with ovalbumin (OVA) used as a model protein antigen. The functional characteristics were examined by dynamic light scattering (DLS), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and scanning electron microscopy (SEM)/scanning transmission electron microscopy (STEM). Stability was examined in the presence of simulated gastric and intestinal fluids, while mucoadhesive properties were evaluated by in vitro mucin binding and ex vivo adhesion on pig oral mucosa tissue. The impact of the formulation and dissolution process on the OVA structure was investigated by sodium dodecyl-polyacrylamide gel electrophoresis (SDS-PAGE) and circular dichroism (CD). Results: The nanoparticles showed a uniform spherical morphology with a maximum protein encapsulation efficiency of 81%, size after OVA loading of between 200 and 400 nm and zeta potential from 10 to 29 mV. An in vitro drug release study suggested successful nanoparticle surface modification by ALG and PEG, showing gastric fluid stability (4 h) and a 96 h sustained OVA release in intestinal fluid, with the nanoparticles maintaining their conformational stability (SDS-PAGE and CD analyses) after release in the intestinal fluid. An in vitro mucin binding study indicated a significant increase in mucin binding from 41 to 63% in ALG-modified nanoparticles and a 27-49% increase in PEG-modified nanoparticles. The ex vivo mucoadhesion showed that the powdered particles adhered to the pig oral mucosa. Conclusion: The ALG and PEG surface modification of chitosan nanoparticles improved the particle stability in both simulated gastric and intestinal fluids and improved the mucoadhesive properties, therefore constituting a potential nanocarrier platform for mucosal protein vaccine delivery.

Development of 3D printed drug-eluting contact lenses.

OBJECTIVES: The aim of the work was to introduce 3D printing technology for the design and fabrication of drug-eluting contact lenses (DECL) for the treatment of glaucoma. The development of 3D printed lenses can effectively overcome drawbacks of existing approaches by using biocompatible medical grade polymers that provide sustained drug release of timolol maleate for extended periods. METHODS: Hot melt extrusion was coupled with fusion deposition modelling (FDM) to produce printable filaments of ethylene-vinyl acetate copolymer-polylactic acid blends at various ratios loaded with timolol maleate. Physicochemical and mechanical characterisation of the printed filaments was used to optimise the printing of the contact lenses. KEY FINDINGS: 3D printed lenses with an aperture (opening) and specified dimensions could be printed using FDM technology. The lenses presented a smooth surface with good printing resolution while providing sustained release of timolol maleate over 3 days. The findings of this study can be used for the development of personalised DECL in the future.

Medicated multi-targeted alginate-based dressings for potential treatment of mixed bacterial-fungal infections in diabetic foot ulcers.

Recently developed medicated dressings target either bacterial or fungal infection only, which is not effective for the treatment of mixed infections common in diabetic foot ulcers (DFUs). This study aimed to develop advanced bioactive alginate-based dressings (films and wafers) to deliver therapeutically relevant doses of ciprofloxacin (CIP) and fluconazole (FLU) to target mixed bacterial and fungal infections in DFUs. The alginate compatibility with the drugs was confirmed by SEM, XRD, FTIR and texture analysis, while the medicated wafers showed better fluid handling properties than the films in the presence of simulated wound fluid. The dressings showed initial fast release of FLU followed by sustained release of CIP which completely eradicated E. coli, S. aureus, P. aeruginosa and reduced fungal load (C. albicans) by 10-fold within 24 h. Moreover, the medicated dressings were biocompatible (>70% cell viability over 72 h) with human primary adult keratinocytes and in-vitro scratch assay showed 65-68% wound closure within 7 days.

Wound dressings as growth factor delivery platforms for chronic wound healing.

Introduction: Years of tissue engineering research have clearly demonstrated the potential of integrating growth factors (GFs) into scaffolds for tissue regeneration, a concept that has recently been applied to wound dressings. The old concept of wound dressings that only take a passive role in wound healing has now been overtaken, and advanced dressings which can take an active part in wound healing, are of current research interest.Areas covered: In this review we will focus on the recent strategies for the delivery of GFs to wound sites with an emphasis on the different approaches used to achieve fine tuning of spatial and temporal concentrations to achieve therapeutic efficacy.Expert opinion: The use of GFs to accelerate wound healing and reduce scar formation is now considered a feasible therapeutic approach in patients with a high risk of infections and complications. The integration of micro - and nanotechnologies into wound dressings could be the key to overcome the inherent instability of GFs and offer adequate control over the release rate. Many investigations have led to encouraging outcomes in various in vitro and in vivo wound models, and it is expected that some of these technologies will satisfy clinical needs and will enter commercialization.

In Vivo Efficacy and Metabolism of the Antimalarial Cycleanine and Improved In Vitro Antiplasmodial Activity of Semisynthetic Analogues.

Bisbenzylisoquinoline (BBIQ) alkaloids are a diverse group of natural products that demonstrate a range of biological activities. In this study, the in vitro antiplasmodial activity of three BBIQ alkaloids (cycleanine [compound 1], isochondodendrine [compound 2], and 2'-norcocsuline [compound 3]) isolated from the Triclisia subcordata Oliv. medicinal plant traditionally used for the treatment of malaria in Nigeria are studied alongside two semisynthetic analogues (compounds 4 and 5) of cycleanine. The antiproliferative effects against a chloroquine-resistant Plasmodium falciparum strain were determined using a SYBR green 1 fluorescence assay. The in vivo antimalarial activity of cycleanine is then investigated in suppressive, prophylactic, and curative murine malaria models after infection with a chloroquine-sensitive Plasmodium berghei strain. BBIQ alkaloids (compounds 1 to 5) exerted in vitro antiplasmodial activities with 50% inhibitory concentration (IC50) at low micromolar concentrations and the two semisynthetic cycleanine analogues showed an improved potency and selectivity compared to those of cycleanine. At oral doses of 25 and 50 mg/kg body weight of infected mice, cycleanine suppressed the levels of parasitemia and increased mean survival times significantly compared to those of the control groups. The metabolites and metabolic pathways of cycleanine were also studied using high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry. Twelve novel metabolites were detected in rats after intragastric administration of cycleanine. The metabolic pathways of cycleanine were demonstrated to involve hydroxylation, dehydrogenation, and demethylation. Overall, these in vitro and in vivo results provide a basis for the future evaluation of cycleanine and its analogues as leads for further development.

Physicochemical characteristics and in vitro permeation of loratadine solid lipid nanoparticles for transdermal delivery.

Aim: To prepare loratadine-loaded solid lipid nanoparticles (SLNs) using a modified two-step ultrasound-assisted phase inversion temperature (PIT) process. Results/methodology: Loratadine was dissolved in beeswax and Tween 80 was dissolved in water. The two phases were mixed together to prepare a water-in-oil emulsion preconcentrate (w/o) at a PIT of 85°C, followed by gradual water addition at 25°C to trigger nanoparticles formation (o/w). Kinetic stability was investigated. No change in the size was observed within 6 months. Fourier-transform infrared spectroscopy demonstrated stability of the emulsions via molecular structure of water at the interface of the o/w nanoemulsions. SLNs enhanced the in vitro skin permeation of loratadine. Conclusion: Stable SLNs were successfully prepared by ultrasound-assisted PIT.

In vitro, ex vivo and in vivo evaluation of taste masked low dose acetylsalicylic acid loaded composite wafers as platforms for buccal administration in geriatric patients with dysphagia.

This study reports the development and characterization of taste masked, freeze-dried composite wafers for potential oral and buccal delivery of low dose aspirin (acetylsalicylic acid) to prevent thrombosis in elderly patients with dysphagia. The wafers were formulated by combining metolose (MET) with carrageenan (CAR), MET with chitosan (CS) at low molecular weight or CAR with CS using 45% v/v ethanol as solvent for complete solubilization of acetylsalicylic acid. Each wafer contained 75 mg of acetylsalicylic acid and sweetener (sucralose, stevia or aspartame) with a drug: sweetener ratio of 1:1 w/w. The formulations were characterized for physical properties using texture analyzer (hardness and mucoadhesion), scanning electron microscopy (SEM), X-ray diffractometry (XRD), Fourier transform infrared (FTIR) spectroscopy, swelling capacity, and in vitro drug dissolution. Further, permeation studies with three different models (Permeapad™ artificial barrier, EpiOral™ and porcine buccal mucosa) using HPLC, cell viability using MTT assay and in vivo taste masking evaluation using human volunteers were undertaken. The sweeteners increased the hardness and adhesion of the wafers, XRD showed the crystalline nature of the samples which was attributed to acetylsalicylic acid, SEM confirmed a compacted polymer matrix due to recrystallized acetylsalicylic acid and sweeteners dispersed over the surface. Drug dissolution studies showed that acetylsalicylic acid was rapidly released in the first 20 min and then continuously over 1 h. EpiOral™ had a higher cumulative permeation than porcine buccal tissue and Permeapad™ artificial barrier, while MTT assay using Vero cells (ATCC® CCL-81) showed that the acetylsalicylic acid loaded formulations were non-toxic. In vivo taste masking study showed the ability of sucralose and aspartame to mask the bitter taste of acetylsalicylic acid and confirm that acetylsalicylic acid loaded MET:CAR, CAR:CS and MET:CS composite wafers containing sucralose or aspartame have potential for buccal delivery of acetylsalicylic acid in geriatric patients with dysphagia.

Bioprinting and Preliminary Testing of Highly Reproducible Novel Bioink for Potential Skin Regeneration.

Three-dimensional (3D) bioprinting is considered as a novel approach in biofabricating cell-laden constructs that could potentially be used to promote skin regeneration following injury. In this study, a novel crosslinked chitosan (CH)-genipin (GE) bioink laden with keratinocyte and human dermal fibroblast cells was developed and printed successfully using an extruder-based bioprinter. By altering the composition and degree of CH-GE crosslinking, bioink printability was further assessed and compared with a commercial bioink. Rheological analysis showed that the viscosity of the optimised bioink was in a suitable range that facilitated reproducible and reliable printing by applying low pressures ranging from 20-40 kPa. The application of low printing pressures proved vital for viability of cells loaded within the bioinks. Further characterisation using MTT assay showed that cells were still viable within the printed construct at 93% despite the crosslinking, processing and after subjecting to physiological conditions for seven days. The morphological study of the printed cells showed that they were mobile within the bioink. Furthermore, the multi-layered 3D printed constructs demonstrated excellent self-supportive structures in a consistent manner.

Surface Modification of Mobile Composition of Matter (MCM)-41 Type Silica Nanoparticles for Potential Oral Mucosa Vaccine Delivery.

Development of mobile composition of matter (MCM)-41 silica nanoparticles faces challenges, e.g. surface charge properties, antigen loading efficiency, protecting from enzymes and harsh GIT environment and effective release at target mucosal site. We report the production and characterization of polymer and amine modified MCM-41 type silica nanoparticles for oral antigen delivery using ovalbumin (OVA) as model antigen. Nanoparticles were characterized by dynamic light scattering (DLS), differential scanning calorimetry (DSC), X-ray diffraction (XRD), scanning electron microscopy (SEM), Brunauer-Emmett-Teller (BET) analysis, circular dichroism (CD), sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), mucin binding, stability in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) and in vitro OVA release in SGF and SIF. Unmodified nanoparticles size of 146 nm increased to 175-321 nm after modification while modified particles remained intact for more than 3 h in SGF and 96 h in SIF (DLS and SEM). Mucin binding proved polyethylene glycol (PEG) and chitosan modified nanoparticles as potential candidates for oral mucosa delivery. Both showed highest OVA encapsulation at 67% and 73%, and sustained OVA release in SIF (96 h) at 65% and 64% respectively. BET results showed that nanopores were not blocked during surface modification. CD and SDS-PAGE showed that OVA conformational structure did not change after release from the nanoparticles.

Formation of stable nanoemulsions by ultrasound-assisted two-step emulsification process for topical drug delivery: Effect of oil phase composition and surfactant concentration and loratadine as ripening inhibitor.

Nanoemulsions are very interesting systems as they offer capacity to encapsulate both hydrophilic and lipophilic molecules in a single particle, as well as the controlled release of chemical moieties initially entrapped in the internal droplets. In this study, we propose a new two-step modified ultrasound-assisted phase inversion approaches-phase inversion temperature (PIT) and self-emulsification, to prepare stable o/w nanoemulsions from a fully water-dilutable microemulsion template for the transdermal delivery of loratadine (a hydrophobe and as Ostwald ripening inhibitor). Firstly, the primary water-in-oil microemulsion concentrate (w/o) was formed using loratadine in the oil phase (oleic acid or coconut oil) and Tween 80 in the aqueous phase and by adjusting the PIT around 85 °C followed by stepwise dilution with water at 25 °C to initiate the formation the nanoemulsions (o/w). To assure the long-term stability, a brief application of low frequency ultrasound was employed. Combining the two low energy methods resulted in nanoemulsions prepared by mixing constant surfactant/oil ratios above the PIT with varying water volume fraction (self-emulsification) during the PIT by stepwise dilution. The kinetic stability was evaluated by measuring the droplet size with time by dynamic light scattering (DLS). The droplet size ranged 15-43 nm and did not exceed 100 nm over the period of 6 months indicating the system had high kinetic stability. Cryo-TEM showed that the nanoemulsions droplets were monodispersed and approaching micellar structure and scale. All nanoemulsions had loratadine crystals formed within 20 days after preparation, which tended to sediment during storage. Nanoemulsions improved the in vitro permeation of loratadine through porcine skin up to 20 times compared to the saturated solution.

Glassy state molecular mobility and its relationship to the physico-mechanical properties of plasticized hydroxypropyl methylcellulose (HPMC) films.

Changes in tensile properties and the glass transition temperature (Tg) of plasticized polymer films are typically attributed to molecular mobility, often with no empirical data to support such an assertion. Herein solvent cast HPMC films containing varying amounts of PEG, as the plasticizer, were used to assess the dependence of tensile properties and the Tg on glassy state molecular mobility. Molecular mobility (molecular relaxation time and temperature) parameters were determined by Thermally Stimulated Current Spectroscopy (TSC). The tensile properties and Tg of the HPMC films were determined by texture analysis and DSC, respectively. Molecular mobilities detected by TSC were cooperative and occurred at temperatures (Tg') well below (113 to 127 °C) the bulk Tg. The relaxation times (τ) were 71 ±â€¯1, 46 ±â€¯1, 42 ±â€¯1, 36 ±â€¯1 and 29 ±â€¯1 s for HPMC films containing 0, 6, 8, 11 and 17% (w/w) PEG, respectively. The Tg and glassy state molecular mobility were found to be intimately linked and demonstrated a linear dependence. While tensile strength was found to be linearly related to molecular relaxation time, tensile elongation and elastic modulus exhibited a non-linear dependence on molecular mobility. The data presented in this work demonstrates the complex nature of the relationship between plasticizer content, molecular mobility, Tg and tensile properties for plasticized polymeric films. It highlights the fact that the dependence of the bulk physico-mechanical properties on glassy state molecular mobility, differ greatly. Therefore, empirical characterization of molecular mobility is important to fully understand and predict the thermo-mechanical behavior of plasticized polymer films. This work demonstrates the unique capability of TSC to provide key information relating to molecular mobility and its influence on the bulk properties of materials. Data generated using TSC could prove useful for stability and performance ranking, in addition to the ability to predict materials behavior using data generated at or below typical storage conditions in the pharmaceutical, food, and polymer industries.

Comparison and process optimization of PLGA, chitosan and silica nanoparticles for potential oral vaccine delivery.

Aim: The study compared performance of nanoparticles prepared from synthetic organic, natural organic and inorganic materials as vaccine delivery platforms. Materials & methods: Various formulation (concentration, polymer/silica:surfactant ratio, solvent) and process parameters (homogenization speed and time, ultrasonication) affecting functional performance characteristics of poly(lactic-co-glycolic acid) (PLGA), chitosan and silica-based nanoparticles containing bovine serum albumin were investigated. Nanoparticles were characterized using dynamic light scattering, x-ray diffraction, scanning/transmission electron microscopy, Fourier transform infrared spectroscopy and in vitro protein release. Results: Critical formulation parameters were surfactant concentration (PLGA, silica) and polymer concentration (chitosan). Optimized nanoparticles were spherical in shape with narrow size distribution and size ranges of 100-300 nm (blank) and 150-400 nm (protein loaded). Protein encapsulation efficiency was 26-75% and released within 48 h in a sustained manner. Conclusion: Critical formulation and process parameters affected size of PLGA, chitosan and silica nanoparticles and protein encapsulation, while silica produced the smallest and most stable nanoparticles.

Oral thin films as a remedy for noncompliance in pediatric and geriatric patients.

Pediatric and geriatric patients experience swallowing difficulties for traditional oral dosage forms, such as tablets. Further, microbial contamination, chemical stability, unpleasant taste and swallowing large volumes of fluids have led to low therapeutic efficacy and patient noncompliance. The emergence of oral thin films has resulted in dramatic improvements in compliance and drug therapy outcomes in pediatric and geriatric patients. Oral thin films do not require water for administration, are readily hydrated upon contact with saliva, adhere to the mucosa and disintegrate ideally under 1 min. This article provides an overview of oral thin films, modern trends in their formulation and characterization, available commercial products, information to fill knowledge gaps and future potential and economic prospects of oral thin film technology, with emphasis on their use in the pediatric and geriatric patient groups.