Spray-Dried Rosuvastatin Nanoparticles for Promoting Hair Growth.

In this research, we examined the effect of rosuvastatin calcium-loaded nanoparticles on the hair growth-promoting activity on Albino rats. Nanoparticles were prepared using 2:1 weight ratio of drug to methyl-ß-cyclodextrin with 10, 20, and 30% stabilizers (phospholipid, polyvinyl pyrrolidone K30, and Compritol 888 ATO) using nanospray dryer. Subsequently, the prepared nanoparticles were evaluated for their process yield, particle size, polydispersity index, zeta potential, and in vitro drug release as well as in vivo studies. The dried nanoparticles showed process yield values up to 84% with particle size values ranging from 218 to 6258 nm, polydispersity index values ranging from 0.32 to 0.99, and zeta potential values ranging from - 6.1 to - 11.9 mV. Combination of methyl-ß-cyclodextrin with 10% polyvinyl pyrrolidone K30 accomplished nanoparticles with the lowest particle size (218 nm) and polydispersity index (0.32) values. These nanoparticles had suitable process yield value (70.5%) and were able to retard drug release. The hair growth-promoting activity for the selected nanoparticles revealed the highest hair length values in Albino rats after 14 days of the hair growth study compared with non-medicated nanoparticles, nanoparticles' physical mixture, rosuvastatin solution, and marketed minoxidil preparation groups as well as the control group. The immunohistochemistry images for both selected nanoparticles and marketed minoxidil groups showed a significant increase in the diameter of hair follicle and percent area fraction of cytokeratin 19 in the outer root sheath of hair follicle compared with other tested groups. Rosuvastatin nanoparticles prepared by nanospray drying technique could be a good competitor to minoxidil for hair growth-promoting activity. Graphical abstract.

Fabrication Strategies of Scaffolds for Delivering Active Ingredients for Tissue Engineering.

Designing scaffolds with optimum properties is an essential factor for tissue engineering success. They can be seeded with isolated cells or loaded with drugs to stimulate the body ability to repair or regenerate the injured tissues by acting as centers for new tissue formation. Recently, scaffolds gained a significant interest as principal candidates for tissue engineering due to overcoming the autograft or allograft's associated problems. The advancement of the tissue engineering field relies mainly on the introduction of new biomaterials for scaffolds' fabrication. This review presents and criticizes different scaffolds' fabrication techniques with particular emphasis on the fibrous, injectable in situ forming, foam, 3D freeze-dried, 3D printed, and 4D scaffolds. This article highlights on scaffolds' composition which would be beneficial for developing scaffolds that could potentially help to meet the demand for both drug delivery and tissue regeneration.

Bioavailability Enhancement of Aripiprazole Via Silicosan Particles: Preparation, Characterization and In vivo Evaluation.

The aim of this study was to design a novel carrier for enhancing the bioavailability of the poorly water-soluble drug, aripiprazole (ARP). Silicosan, the applied carrier, was obtained by chemical interaction between tetraethyl orthosilicate (TEOS) and chitosan HCl. Different ARP-loaded silicosan particles were successfully prepared in absence and presence of one of the following surfactants; Tween 80, Poloxamer 407 and cetyltrimethylammonium bromide (CTAB). The prepared ARP-loaded silicosan particles were thoroughly investigated for their structures using FTIR, XRD, and DSC analysis as well as their particle size, zeta potential, flowability, drug content, and in vitro drug release efficiencies. The prepared ARP-loaded silicosan particles were characterized by amorphous structure, high drug entrapment efficiency and a remarkable improvement in the release of aripiprazole in simulated gastric fluid. SEM and EDX revealed that the morphology and silica atom content in the prepared ARP-loaded silicosan particles were affected by the used surfactant in their formulations. The selected ARP-loaded silicosan particles were subjected to in vivo study using rabbits. The obtained pharmacokinetic results showed that the relative bioavailability for orally administered ARP-loaded silicosan particles (SC-2-CTAB) was 66% higher relative to the oral suspension (AUC0-10h was 16.38 ± 3.21 and 27.23 ± 2.35 ng.h/mL for drug powder and SC-2-CTAB formulation, respectively). The obtained results suggested the unique-structured silicosan particles to be used as successful vehicle for ARP.

Non-ionic Surfactant Based In Situ Forming Vesicles as Controlled Parenteral Delivery Systems.

Non-ionic surfactant (NIS) based in situ forming vesicles (ISVs) present an affordable alternative to the traditional systems for the parenteral control of drug release. In this work, NIS based ISVs encapsulating tenoxicam were prepared using the emulsion method. Tenoxicam-loaded ISVs were prepared using a 22.31 full factorial experimental design, where three factors were evaluated as independent variables; type of NIS (A), molar ratio of NIS to Tween®80 (B), and phase ratio of the internal ethyl acetate to the external Captex® oil phase (C). Percentage drug released after 1 h, particle size of the obtained vesicles and mean dissolution time were chosen as the dependent variables. Selected formulation was subjected to morphological investigation, injectability, viscosity measurements, and solid state characterization. Optimum formulation showed spherical nano-vesicles in the size of 379.08 nm with an initial drug release of 37.32% in the first hour followed by a sustained drug release pattern for 6 days. DSC analysis of the optimized formulation confirmed the presence of the drug in an amorphous form with the nano-vesicles. Biological evaluation of the selected formulation was performed on New Zealand rabbits by IM injection. The prepared ISVs exhibited a 45- and 28-fold larger AUC and MRT values, respectively, compared to those of the drug suspension. The obtained findings boost the use of ISVs for the treatment of many chronic inflammatory conditions.

Nanostructured lipid carriers as semisolid topical delivery formulations for diflucortolone valerate.

CONTEXT: Topical treatment of skin disease needs to be strategic to ensure high drug concentration in the skin with minimum systemic absorption. OBJECTIVE: The aim of this study was to produce semisolid nanostructured lipid carrier (NLC) formulations, for topical delivery of the corticosteroid drug, diflucortolone valerate (DFV), with minimum systemic absorption. METHOD: NLC formulations were developed using a high shear homogenization combined with sonication, using Precirol® ATO5 or Tristearin® as the solid lipid, Capryol™ or isopropyl myristate as the liquid lipid and Poloxamer® 407 as surfactant. The present study addresses the influence of different formulations composition as solid lipid, liquid lipid types and concentrations on the physicochemical properties and drug release profile from NLCs. RESULTS AND DISCUSSION: DFV-loaded NLC formulations possessed average particle size ranging from 160.40 nm to 743.7 nm with narrow polydispersity index. The encapsulation efficiency was improved by adding the lipid-based surfactants (Labrasol® and Labrafil® M1944CS) to reach 68%. The drug release from the investigated NLC formulations showed a prolonged release up to 12 h. The dermatopharmacokinetic study revealed an improvement in drug deposition in the skin with the optimized DFV-loaded NLC formulation, in contrast to a commercial formulation. CONCLUSION: NLC provides a promising nanocarrier system that work as reservoir for targeting topical delivery of DFV.

PLGA Nanoparticles as Subconjunctival Injection for Management of Glaucoma.

Nanoparticles fabricated from the biodegradable and biocompatible polymer, polylactic-co-glycolic acid (PLGA), could be a promising system for targeting ocular drug delivery. The objective of this work was to investigate the possibility of encapsulating brinzolamide in PLGA nanoparticles in order to be applied as a subconjunctival injection that could represent a starting point for developing new therapeutic strategies against increase in ocular pressure. The brinzolamide-loaded PLGA nanoparticles were fabricated using emulsion-diffusion-evaporation method with varying concentrations of Tween 80 or poloxamer 188 (Plx) in aqueous and organic phases. The nanoparticles were characterized in terms of particle size and size distribution, entrapment efficiency and in-vitro drug release pattern as well as DSC and X-ray analysis. Nanoparticles prepared using Tween 80 in the aqueous phase showed higher encapsulation efficiency and smaller particle size-values compared to those prepared using Plx. Furthermore, the addition of Plx 188 or Brij 97 to the organic phase in the formulation containing Tween 80 in the aqueous phase led to an increase in the particle diameter-values of the obtained nanoparticles. The nanoparticles had the capacity to release the brinzolamide in a biphasic release profile. The nanoparticles were spherical in shape and the drug was entraped in the nanoparticles in an amorphous form. Selected nanoparticles, injected subconjunctivally in normotensive Albino rabbits, were able to reduce the IOP for up to 10 days. Nanoparticles loaded with brinzolamide with lower particle size were able to reduce the IOP for longer period compared to those with higher particle size. Histopathological studies for the anterior cross sections of the rabbits' eyes revealed that the tested nanoparticles were compatible with the ocular tissue. The overall results support that PLGA nanoparticles, applied as subconjunctival injection, can be considered as a promising carrier for ocular brinzolamide delivery with targeting delivery of the drug to the eye tissues.

Design and In Vitro/In Vivo Evaluation of Ultra-Thin Mucoadhesive Buccal Film Containing Fluticasone Propionate.

Fluticasone propionate is a synthetic corticosteroid drug distinguished by its potent anti-inflammatory action with low systemic side effects in comparison to other corticosteroids making it a potential drug for local buccal delivery. The aim of the present study was to design mucoadhesive buccal film containing fluticasone that is aesthetically acceptable and could maintain local drug release for a sustained period to manage the sign and symptoms of severe erosive mouth lesions. Solvent casting technique was used in film preparation. Different polymeric blends were used either alone or in combination with mucoadhesive polymers, sodium carboxymethyl cellulose (SCMC), or Carbopol 971P at different concentrations. The physicochemical properties, in vitro mucoadhesion time as well as the drug release properties for all prepared formulations were determined. Selected formulations with adequate properties were further examined by differential scanning calorimetry (DSC) and X-ray diffraction (XRD) and subjected to in vivo evaluation. Films containing hydroxypropyl methylcellulose (HPMC)/ethyl cellulose (EC) showed acceptable physicochemical properties, homogenous drug distribution, convenient mucoadhesion time, moderate swelling as well as sustained drug release up to 12 h. The biological performance of these formulations was assessed on healthy human volunteers and compared with a prepared mouthwash which showed enhanced pharmacokinetic parameters for the selected films in comparison to the mouthwash. The results revealed that the optimized formulation containing HPMC/EC and 10% SCMC could successfully achieve sustained drug release for 10 h which is considered promising for local treatment of severe mouth lesions.

Bioactive/Natural Polymeric Scaffolds Loaded with Ciprofloxacin for Treatment of Osteomyelitis.

Local delivery of antibiotic into injured bone is a demand. In this work, different scaffolds of chitosan (C) with or without bioactive glass (G) were prepared using the freeze-drying technique in 2:1, 1:1, and 1:2 weight ratios. Chitosan scaffolds and selected formulas of chitosan to bioglass were loaded with ciprofloxacin in 5%, 10%, and 20% w/w. Scaffold morphology showed an interconnected porous structure, where the glass particles were homogeneously dispersed in the chitosan matrix. The kinetic study confirmed that the scaffold containing 1:2 weight ratio of chitosan to glass (CG12) showed optimal bioactivity with good compromise between Ca and P uptake capacities and Si release rate. Chitosan/bioactive glass scaffolds showed larger t 50 values indicating less burst drug release followed by a sustained drug release profile compared to that of chitosan scaffolds. The cell growth, migration, adhesion, and invasion were enhanced onto CG12 scaffold surfaces. Samples of CG12 scaffolds with or without 5% drug induced vascular endothelial growth factor (VEGF), while those containing 10% drug diminished VEGF level. Only CG12 induced the cell differentiation (alkaline phosphatase activity). In conclusion, CG12 containing 5% drug can be considered a biocompatible carrier which would help in the localized osteomyelitis treatment.

Nano Spray Drying Technique as a Novel Approach To Formulate Stable Econazole Nitrate Nanosuspension Formulations for Ocular Use.

The effect of using methyl-ß-cyclodextrin and hydroxypropyl-ß-cyclodextrin as carriers for econazole nitrate nanoparticles prepared by nano spray dryer was explored in this work. Stabilizers, namely, poly(ethylene oxide), polyvinylpyrrolidone k30, poloxamer 407, Tween 80, and Cremophor EL, were used. The nano spray dried formulations revealed almost spherical particles with an average particle size values ranging from 121 to 1565 nm and zeta potential values ranging from -0.8 to -2.5 mV. The yield values for the obtained formulations reached 80%. The presence of the drug in the amorphous state within the nanosuspension matrix system significantly improved drug release compared to that for pure drug. Combination of hydroxypropyl-ß-cyclodextrin with Tween 80 achieved an important role for preserving the econazole nanosuspension from aggregation during storage for one year at room temperature as well as improving drug release from the nanosuspension. This selected formulation was suspended in chitosan HCl to increase drug release and bioavailability. The in vivo evaluation on albino rabbit's eyes demonstrated distinctly superior bioavailability of the selected formulation suspended in chitosan compared to its counterpart formulation suspended in buffer and crude drug suspension due to its mucoadhesive properties and nanosize. The nano spray dryer could serve as a one step technique toward formulating stable and effective nanosuspensions.

A Novel Method for Preparing Surface-Modified Fluocinolone Acetonide Loaded PLGA Nanoparticles for Ocular Use: In Vitro and In Vivo Evaluations.

Our objective was to prepare nanoparticulate system using a simple yet attractive innovated method as an ophthalmic delivery system for fluocinolone acetonide to improve its ocular bioavailability. Poly(lactic-co-glycolic acid) (PLGA) nanoparticles were prepared by adopting thin film hydration method using PLGA/poloxamer 407 in weight ratios of 1:5 and 1:10. PLGA was used in 75/25 and 50/50 copolymer molar ratio of DL-lactide/glycolide. Results revealed that using PLGA with lower glycolic acid monomer ratio exhibited high particle size (PS), zeta potential (ZP) and drug encapsulation efficiency (EE) values with slow drug release pattern. Also, doubling the drug concentration during nanoparticles preparation ameliorated its EE to reach almost 100%. Furthermore, studies for separating the un-entrapped drug in nanoparticles using centrifugation method at 20,000 rpm for 30 min showed that the separated clear supernatant contained nanoparticles encapsulating an important drug amount. Therefore, separation of un-entrapped drug was carried out by filtrating the preparation using 20-25 µm pore size filter paper to avoid drug loss. Aiming to increase the PLGA nanoparticles mucoadhesion ability, surface modification of selected formulation was done using different amount of stearylamine and chitosan HCl. Nanoparticles coated with 0.1% w/v chitosan HCl attained most suitable results of PS, ZP and EE values as well as high drug release properties. Transmission electron microphotographs illustrated the deposition of chitosan molecules on the nanoparticles surfaces. Pharmacokinetic studies on Albino rabbit's eyes using HPLC indicated that the prepared novel chitosan-coated PLGA nanoparticles subjected to separation by filtration showed rapid and extended drug delivery to the eye.

PLGA and PDMS-based in situ forming implants loaded with rosuvastatin and copper-selenium nanoparticles: a promising dual-effect formulation with augmented antimicrobial and cytotoxic activity in breast cancer cells.

Breast cancer is among the most prevalent tumors worldwide. In this study, in-situ forming implants (ISFIs) containing rosuvastatin calcium were prepared using three types of poly (D, L-lactic-co-glycolic acid) (PLGA), namely, PLGA 50/50 with ester terminal and PLGA 75/25 with ester or acid terminal. Additionally, polydimethylsiloxane (PDMS) was added in concentrations of 0, 10, 20, and 30% w/v to accelerate matrix formation. The prepared ISFIs were characterized for their rheological behaviors, rate of matrix formation, and in-vitro drug release. All the prepared formulations revealed a Newtonian flow with a matrix formation rate between 0.017 and 0.059 mm/min. Generally, increasing the concentration of PDMS increased the matrix formation rate. The prepared implants' release efficiency values ranged between 46.39 and 89.75%. The ISFI containing PLGA 50/50 with 30% PDMS was selected for further testing, as it has the highest matrix formation rate and a promising release efficiency value. Copper-selenium nanoparticles were prepared with two different particle sizes (560 and 383 nm for CS1 and CS2, respectively) and loaded into the selected formulation to enhance its anticancer activity. The unloaded and loaded implants with rosuvastatin and copper-selenium nanoparticles were evaluated for their antibacterial activity, against Gram-positive and negative microorganisms, and anticancer efficacy, against MCF-7 and MDA-MB-231 cell lines. The results confirmed the potency of rosuvastatin calcium against cancer cells and the synergistic effect when loaded with smaller particle sizes of copper-selenium nanoparticles. This formulation holds a considerable potential for efficient breast cancer therapy.

Investigation of the Electrokinetic Potential of Granules and Optimization of the Pelletization Method Using the Quality by Design Approach.

The preparation of pellets using a high-shear granulator in a rapid single-step is considered a good economic alternative to the extrusion spheronization process. As process parameters and material attributes greatly affect pellet qualities, successful process optimization plays a vital role in producing pellet dosage forms with the required critical quality attributes. This study was aimed at the development and optimization of the pelletization technique with the Pro-CepT granulator. According to the quality by design (QbD) and screening design results, chopper speed, the volume of the granulating liquid, binder amount, and impeller speed were selected as the highest risk variables for a two-level full factorial design and central composite design, which were applied to the formula of microcrystalline cellulose, mannitol, and with a binding aqueous polyvinylpyrrolidone solution. The design space was estimated based on physical response results, including the total yield of the required size, hardness, and aspect ratio. The optimized point was tested with two different types of active ingredients. Amlodipine and hydrochlorothiazide were selected as model drugs and were loaded into an optimized formulation. The kinetics of the release of the active agent was examined and found that the results show a correlation with the electrokinetic potential because amlodipine besylate can be adsorbed on the surface of the MCC, while hydrochlorothiazide less so; therefore, in this case, the release of the active agent increases. The research results revealed no significant differences between plain and model drug pellets, except for hydrochlorothiazide yield percent, in addition to acceptable content uniformity and dissolution enhancement.

Risedronate-loaded aerogel scaffolds for bone regeneration.

Sugarcane bagasse-derived nanofibrillated cellulose (NFC), a type of cellulose with a fibrous structure, is potentially used in the pharmaceutical field. Regeneration of this cellulose using a green process offers a more accessible and less ordered cellulose II structure (amorphous cellulose; AmC). Furthermore, the preparation of cross-linked cellulose (NFC/AmC) provides a dual advantage by building a structural block that could exhibit distinct mechanical properties. 3D aerogel scaffolds loaded with risedronate were prepared in our study using NFC or cross-linked cellulose (NFC/AmC), then combined with different concentrations of chitosan. Results proved that the aerogel scaffolds composed of NFC and chitosan had significantly improved the mechanical properties and retarded drug release compared to all other fabricated aerogel scaffolds. The aerogel scaffolds containing the highest concentration of chitosan (SC-T3) attained the highest compressive strength and mean release time values (415 ± 41.80 kPa and 2.61 ± 0.23 h, respectively). Scanning electron microscope images proved the uniform highly porous microstructure of SC-T3 with interconnectedness. All the tested medicated as well as unmedicated aerogel scaffolds had the ability to regenerate bone as assessed using the MG-63 cell line, with the former attaining a higher effect than the latter. However, SC-T3 aerogel scaffolds possessed a lower regenerative effect than those composed of NFC only. This study highlights the promising approach of the use of biopolymers derived from agro-wastes for tissue engineering.

Nanofibrous Polycaprolactone Membrane with Bioactive Glass and Atorvastatin for Wound Healing: Preparation and Characterization.

Skin wound healing is one of the most challenging processes for skin reconstruction, especially after severe injuries. In our study, nanofiber membranes were prepared for wound healing using an electrospinning process, where the prepared nanofibers were made of different weight ratios of polycaprolactone and bioactive glass that can induce the growth of new tissue. The membranes showed smooth and uniform nanofibers with an average diameter of 118 nm. FTIR and XRD results indicated no chemical interactions of polycaprolactone and bioactive glass and an increase in polycaprolactone crystallinity by the incorporation of bioactive glass nanoparticles. Nanofibers containing 5% w/w of bioactive glass were selected to be loaded with atorvastatin, considering their best mechanical properties compared to the other prepared nanofibers (3, 10, and 20% w/w bioactive glass). Atorvastatin can speed up the tissue healing process, and it was loaded into the selected nanofibers using a dip-coating technique with ethyl cellulose as a coating polymer. The study of the in vitro drug release found that atorvastatin-loaded nanofibers with a 10% coating polymer revealed gradual drug release compared to the non-coated nanofibers and nanofibers coated with 5% ethyl cellulose. Integration of atorvastatin and bioactive glass with polycaprolactone nanofibers showed superior wound closure results in the human skin fibroblast cell line. The results from this study highlight the ability of polycaprolactone-bioactive glass-based fibers loaded with atorvastatin to stimulate skin wound healing.

Brain delivery of olanzapine by intranasal administration of transfersomal vesicles.

The aim of this study was to investigate the presence of a possible direct correlation between vesicle elasticity and the amount of drug reaching the brain intranasally. Therefore, transfersomes were developed using phosphatidylcholine (PC) as the lipid matrix and sodium deoxycholate (SDC), Span® 60, Cremophor® EL, Brij® 58, and Brij® 72 as surfactants. The influence of the type of surfactant and PC-to-surfactant ratio on vesicle morphology, size, membrane elasticity, drug entrapment, and in vitro drug release was studied. The prepared transfersomes were mainly spherical in shape, with diameters ranging from 310 to 885 nm. Transfersomes containing SDC and Span 60 with optimum lipid-to-surfactant molar ratio showed suitable diameters (410 and 380 nm, respectively) and deformability indices (17.68 and 20.76 mL/sec, respectively). Values for absolute drug bioavailability in rat plasma for transfersomes containing SDC and those containing Span 60 were 24.75 and 51.35%, whereas AUC(0-360 min) values in rat brain were 22,334.6 and 36,486.3 ng/mL/min, respectively. The present study revealed that the deformability index is a parameter having a direct relation with the amount of the drug delivered to the brain by the nasal route.

Fast relief from migraine attacks using fast-disintegrating sublingual zolmitriptan tablets.

Zolmitriptan is a potent molecule for treatment of migraine. Its current oral therapies present drawbacks such as slow onset of action, low bioavailability and large inter-subject variability. Fast disintegrating sublingual zolmitriptan tablet (FDST) using freeze-drying technique has been developed to enhance tablet disintegration and dissolution with the intention of speeding drug absorption and onset of effect, hence mitigating the effects on the gastrointestinal dysmotility that typically accompanies the migraine attack. The FDSTs were prepared using different concentrations of gelatin as binder and mannitol or L-alanine as matrix supporting/disintegration enhancing agents. The effect of formulation variables on the physicochemical and solid-state properties, as well as the dissolution behaviour of the tablets, was studied. The formulated FDSTs disintegrated within 30 s and showed significantly faster dissolution rate of zolmitriptan compared to the zolmitriptan oral tablet. Tablet containing 2% gelatin and mannitol showed acceptable weight variation, drug content and friability values. Furthermore, it had a low in-vitro and in-vivo disintegration time (11 s) and it reached 100% of drug release within 30 s. This sublingual formulation gave faster and higher zolmitriptan plasma concentration in rabbits compared to the oral zolmetriptan market product. Zolmitriptan FDST may therefore constitute an advance in the management of acute migraine attacks.

Merits and advances of microfluidics in the pharmaceutical field: design technologies and future prospects.

Microfluidics is used to manipulate fluid flow in micro-channels to fabricate drug delivery vesicles in a uniform tunable size. Thanks to their designs, microfluidic technology provides an alternative and versatile platform over traditional formulation methods of nanoparticles. Understanding the factors that affect the formulation of nanoparticles can guide the proper selection of microfluidic design and the operating parameters aiming at producing nanoparticles with reproducible properties. This review introduces the microfluidic systems' continuous flow (single-phase) and segmented flow (multiphase) and their different mixing parameters and mechanisms. Furthermore, microfluidic approaches for efficient production of nanoparticles as surface modification, anti-fouling, and post-microfluidic treatment are summarized. The review sheds light on the used microfluidic systems and operation parameters applied to prepare and fine-tune nanoparticles like lipid, poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles as well as cross-linked nanoparticles. The approaches for scale-up production using microfluidics for clinical or industrial use are also highlighted. Furthermore, the use of microfluidics in preparing novel micro/nanofluidic drug delivery systems is presented. In conclusion, the characteristic vital features of microfluidics offer the ability to develop precise and efficient drug delivery nanoparticles.

PLGA-modified Syloid®-based microparticles for the ocular delivery of terconazole: in-vitro and in-vivo investigations.

The eye is an invulnerable organ with intrinsic anatomical and physiological barriers, hindering the development of a pioneer ocular formulation. The aim of this work was to develop an efficient ocular delivery system that can augment the ocular bioavailability of the antifungal drug, terconazole. Mesoporous silica microparticles, Syloid® 244 FP were utilized as the carrier system for terconazole. Preliminary studies were carried out using different drug:Syloid® weight ratios. The optimum weight ratio was mixed with various concentrations (30 and 60%w/w) of poly (lactic-co-glycolic acid) (PLGA), ester or acid-capped and with different monomers-ratio (50:50 and 75:25) using the nano-spray dryer. Results revealed the superiority of drug:Syloid® weight ratio of 1:2 in terms of yield percentage (Y%), SPAN and drug content percentage (DC%). Furthermore, incorporation of PLGA with lower glycolic acid monomer-ratio significantly increased Y%. In contrast, increasing the glycolic acid monomer-ratio resulted in higher DC% and release efficiency percentage (RE%). Additionally, doubling PLGA concentration significantly reduced Y%, DC%, drug loading percentage (DL%) and RE%. Applying desirability function in terms of increasing DC%, DL% besides RE% and decreasing SPAN, the selected formulation was chosen for DSC, XRD and SEM investigations. Results confirmed the successful loading of amorphized terconazole on PLGA-modified Syloid® microparticles. Moreover, pharmacokinetic studies for the chosen formulation on male Albino rabbits' eyes revealed a 2, 6.7 and 25.3-fold increase in mean residence time, Cmax and AUC0-24-values, respectively, compared to the drug suspension. PLGA-modified Syloid® microparticles represent a potential option to augment the bioavailability of ocular drugs.

Cyclodextrin Stabilized Freeze-Dried Silica/Chitosan Nanoparticles for Improved Terconazole Ocular Bioavailability.

This research assesses the beneficial effects of loading terconazole, a poorly water-soluble antifungal drug in silica/chitosan nanoparticles (SCNs) for ocular delivery. Nanoparticles were fabricated by the simple mixing of tetraethyl ortho silicate (TEOS) and chitosan HCl as sources of silica and nitrogen, respectively, along with alcoholic drug solution in different concentrations. Freeze-dried nanoparticles were fabricated using cyclodextrins as cryoprotectants. SCNs were assessed for their particle size, PDI, yield, drug loading and in vitro release studies. A 23.31 full factorial experimental design was constructed to optimize the prepared SCNs. DSC, XRD, FTIR, in addition to morphological scanning were performed on the optimized nanoparticles followed by an investigation of their pharmacokinetic parameters after topical ocular application in male Albino rabbits. The results reveal that increasing the water content in the preparations causes an increase in the yield and size of nanoparticles. On the other hand, increasing the TEOS content in the preparations, caused a decrease in the yield and size of nanoparticles. The optimized formulation possessed excellent mucoadhesive properties with potential safety concerning the investigated rabbit eye tissues. The higher Cmax and AUC0-24 values coupled with a longer tmax value compared to the drug suspension in the rabbits' eyes indicated the potential of SCNs as promising ocular carriers for poorly water-soluble drugs, such as terconazole.

Nanofibrillated cellulose/glucosamine 3D aerogel implants loaded with rosuvastatin and bioactive ceramic for dental socket preservation.

Recycling of agro-wastes presents a great economic and ecologic value. In this study, TEMPO-oxidized nanofibrillated cellulose (TONFC) originating from sugarcane bagasse pulp was exploited in regenerative medicine. TONFC in combination with glucosamine HCl (G) were used to prepare a 3D aerogel implant loaded with rosuvastatin as an integrative approach for extraction-socket healing. Comparing the prepared devices, aerogel composed of TONFC: G (4:1 wt ratio) had the best mechanical properties and integrity. Strontium borate-based bioactive ceramic particles were prepared and characterized for crystal structure, shape, porosity, and zeta potential. The particles had a crystalline diffraction pattern relative to Sr3B2O6, and they were rod in shape with nanopores with a zeta potential value of -16 mV. The prepared bioactive ceramic (BC) was then added in different concentrations (3 or 6% w/w) to the selected aerogel implant. The BC had a concentration-dependent effect on the aerogel properties as it ameliorated its mechanical performance (compressive strength = 90 and 150 kPa for 3 and 6%, respectively) and retarded drug release (mean release time = 2.34 and 3.4 h for 3 and 6%, respectively) (p < 0.05). The microphotograph of the selected aerogel implant loaded with BC showed a rough surface with an interconnective porous structure. During cell biology testing, the selected implant loaded with the lower BC concentration had the highest ability to increase MG-63 cells proliferation. In conclusion, TONFC is a promising material to formulate rosuvastatin-loaded aerogel implant with the aid of glucosamine and bioactive ceramic for dental socket preservation.