Synergistic approach for acne vulgaris treatment using glycerosomes loaded with lincomycin and lauric acid: Formulation, in silico, in vitro, LC-MS/MS skin deposition assay and in vivo evaluation.

This study aims to develop a pharmaceutical formulation that combines the potent antibacterial effect of lincomycin and lauric acid against Cutibacterium acnes (C. acnes), a bacterium implicated in acne. The selection of lauric acid was based on an in silico study, which suggested that its interaction with specific protein targets of C. acnes may contribute to its synergistic antibacterial and anti-inflammatory effects. To achieve our aim, glycerosomes were fabricated with the incorporation of lauric acid as a main constituent of glycerosomes vesicular membrane along with cholesterol and phospholipon 90H, while lincomycin was entrapped within the aqueous cavities. Glycerol is expected to enhance the cutaneous absorption of the active moieties via hydrating the skin. Optimization of lincomycin-loaded glycerosomes (LM-GSs) was conducted using a mixed factorial experimental design. The optimized formulation; LM-GS4 composed of equal ratios of cholesterol:phospholipon90H:Lauric acid, demonstrated a size of 490 ± 17.5 nm, entrapment efficiency-values of 90 ± 1.4 % for lincomycin, and97 ± 0.2 % for lauric acid, and a surface charge of -30.2 ± 0.5mV. To facilitate its application on the skin, the optimized formulation was incorporated into a carbopol hydrogel. The formed hydrogel exhibited a pH value of 5.95 ± 0.03 characteristic of pH-balanced skincare and a shear-thinning non-Newtonian pseudoplastic flow. Skin deposition of lincomycin was assessed using an in-house developed and validated LC-MS/MS method employing gradient elution and electrospray ionization detection. Results revealed that LM-GS4 hydrogel exhibited a two-fold increase in skin deposition of lincomycin compared to lincomycin hydrogel, indicating improved skin penetration and sustained release. The synergistic healing effect of LM-GS4 was evidenced by a reduction in inflammation, bacterial load, and improved histopathological changes in an acne mouse model. In conclusion, the proposed formulation demonstrated promising potential as a topical treatment for acne. It effectively enhanced the cutaneous absorption of lincomycin, exhibited favorable physical properties, and synergistic antibacterial and healing effects. This study provides valuable insights for the development of an effective therapeutic approach for acne management.

Investigating the Targeting Power to Brain Tissues of Intranasal Rasagiline Mesylate-Loaded Transferosomal In Situ Gel for Efficient Treatment of Parkinson's Disease.

Rasagiline mesylate (RSM) is a hydrophilic drug with poor oral bioavailability (36%) because of hepatic first-pass metabolism. The present study focuses on delivering RSM directly to the brain through its inclusion within transferosomal in situ gel administered through the intranasal (IN) route. Transferosomes were formed by the thin-film hydration method with the aid of Design-Expert® software by varying the edge activator (EA) type in the absence or presence of cholesterol. By desirability calculations, the optimum formulation was composed of phosphatidylcholine and sodium deoxycholate as an EA (5:1% w/w) with no cholesterol. The optimum formulation was 198.63 ± 34.98 nm in size and displayed an entrapment efficiency of 95.73 ± 0.09%. Transmission electron microscopy revealed discrete and spherical vesicles. Optimized transferosomes were further incorporated into an in situ gel composed of 0.5% pectin, 15% Pluronic® F-127, and 5% Pluronic® F-68 and tested for the in vivo performance. The systemic as well as brain kinetics were assessed in rats by comparing the IN-administered in situ gel to the IV aqueous solution. The optimum in situ gel showed safety and biocompatibility on rats' nasal mucosa with enhanced brain bioavailability (131.17%). Drug targeting efficiency and direct transport percentage indices (304.53% and 67.16%, respectively) supported successful brain targeting offering direct nose-to-brain drug delivery.

Nose-to-brain delivery of galantamine loaded nanospray dried polyacrylic acid/taurodeoxycholate mixed matrix as a protective therapy in lipopolysaccharide-induced Alzheimer's in mice model.

One of the promising drug delivery approaches is performed by nanosizing the administered drug product using the nanospray drying technique. In this study, a combination of several formulation factors was integrated and exploited to augment the bioavailability of galantamine hydrobromide (GAL) via the intranasal route. Nanosized polymeric particles were fabricated using the mucoadhesive polymer, polyacrylic acid (PAA), and the permeability booster, sodium taurodeoxycholate (TDC). First, a preliminary study was conducted to adjust the nanospray drying conditions. Then, formulations were prepared on the basis of a mixed factorial experimental design and further analyzed using Design Expert® software. Different responses were investigated: particle size, polydispersity index, spray rate, drying efficiency, and percent yield. The optimized formulation was further assessed for physical morphology using the scanning electron microscope, flowability, in vitro drug release, and in vivo brain cell uptake using confocal laser scanning microscopy. The promising formulation (F6), composed of equal ratio of PAA and TDC and 20 mg GAL, exhibited a particle size of 185.55 ± 4.3 nm, polydispersity index of 0.413 ± 0.02, and yield-value of 69.58 ± 5.82 %. It also displayed good flowability, complete drug release within 2 h, and enhanced in vivo fluorescent dye uptake and penetration in brain cells. The efficacy of the optimized formulation was examined using lipopolysaccharide-induced Alzheimer's in mice. Results revealed the advantageous influence of the optimized formulation (F6) through downregulation of NF-κß, IL-1ß and GFAP as well as upregulating TGF-1ß in adult mice.

Budesonide-Loaded Bilosomes as a Targeted Delivery Therapeutic Approach Against Acute Lung Injury in Rats.

Budesonide (BUD), a glucocorticoids drug, inhibits all steps in the inflammatory response. It can reduce and treat inflammation and other symptoms associated with acute lung injury such as COVID-19. Loading BUD into bilosomes could boost its therapeutic activity, and lessen its frequent administration and side effects. Different bilosomal formulations were prepared where the independent variables were lipid type (Cholesterol, Phospholipon 80H, L-alpha phosphatidylcholine, and Lipoid S45), bile salt type (Na cholate and Na deoxycholate), and drug concentration (10, 20 mg). The measured responses were: vesicle size, entrapment efficiency, and release efficiency. One optimum formulation (composed of cholesterol, Na cholate, and 10 mg of BUD) was selected and investigated for its anti-inflammatory efficacy in vivo using Wistar albino male rats. Randomly allocated rats were distributed into four groups: The first: normal control group and received intranasal saline, the second one acted as the acute lung injury model received intranasal single dose of 2 mg/kg potassium dichromate (PD). Whereas the third and fourth groups received the market product (Pulmicort® nebulising suspension 0.5 mg/ml) and the optimized formulation (0.5 mg/kg; intranasal) for 7 days after PD instillation, respectively. Results showed that the optimized formulation decreased the pro-inflammatory cytokines TNF-α, and TGF-ß contents as well as reduced PKC content in lung. These findings suggest the potentiality of BUD-loaded bilosomes for the treatment of acute lung injury with the ability of inhibiting the pro-inflammatory cytokines induced COVID-19.

Optimized copolymeric microstructured platforms for smart controlled delivery of an anticoagulant drug: Preparation, in vitro assessment and crossover study in healthy adult human volunteers.

In the present study, novel micro-structured copolymeric carriers were developed based on the grafting technology where acrylamide was chemically crosslinked with different types of Eudragits® (NE30D, L100, RL30D, or RS30D) based on a 41*21 factorial design. The designed systems efficiently engulfed the anticoagulant drug dipyridamole (DIP), within their formed entangled mesh of crosslinked polymeric network. An optimized formulation, ECOP4 with a desirability-value of 0.706, (in which DIP is engulfed within a copolymeric network of acrylamide and Eudragit® RS30D) showed high engulfment capacity (97.13 ± 1.34%) and controlled DIP release over 8 h. FTIR studies revealed absence of interactions between DIP and the formed copolymer. ECOP4 was further inserted within an easily-administered safe raft forming system composed of a mixture of LM-pectin and gellan gum. A pharmacokinetic study was performed using human volunteers to determine DIP concentration in their plasma after administering the designed formulation using the high-performance liquid chromatography (HPLC) method. A crossover design was adopted comparing the designed formulation with Persantin® 25 mg tablets as a reference standard. Superior results were obtained for the optimized formulation regarding the measured pharmacokinetic parameters (AUC0-24h, Cmax, and Tmax) with a 2.31 fold increase in relative bioavailability, which reveals the usefulness of the designed grafted dipyridamole formulation in site-specific delivery system.

Micellar buccal film for safe and effective control of seizures: Preparation, in vitro characterization, ex vivo permeation studies and in vivo assessment.

The current research article focused on formulating an easily applied, water-based buccal film loaded with the antiepileptic drug, lamotrigine (LTG). The designed film can be comfortably administered by epileptic patients to ensure a controllable therapeutic efficacy against seizures. The solubility of LTG in water was significantly improved by micellar solubilization. Upon testing several surfactants, three of them (Synperonic PE/P84, Brij L23, and Brij 78) achieved maximum possible solubility for LTG and were characterized for their micellar size, cloud point, and % transmittance. Selected micellar systems were incorporated within a buccal film prepared using solvent casting method based on either gelatin or polyvinylpyrrolidone (3%w/v) with 1.5%w/v propylene glycol as a plasticizer. Different micellar films were characterized for their physicochemical characteristics, swelling index, folding endurance, drug content uniformity, and in vitro LTG release. From the tested formulations, one formulation; LTG-BF1 (in which Brij 78 was used for the micellar solubilization and gelatin as the matrix former), was selected as the optimum and extensively studied for mucoadhesion, ex vivo permeation studies by Franz diffusion cells and confocal laser scanning microscopy. Results showed superior enhanced permeation of micellar film. LTG-BF1 was evaluated for the in vivo performance using rats. Status epilepticus was induced in rats by injecting Pentylenetetrazol (PTZ) i.p. at an initial dose of 30 mg/kg, followed by 10 mg/kg every10 min till 60 min. A group of rats receiving the designed buccal formulation (20 mg/kg) was compared with a group receiving the same dose of the oral market product and the normal control and PTZ groups. Rats receiving LTG-BF1 recorded reduced seizure scores at all stages, longer latency time, and higher threshold PTZ dose compared to PTZ and market product groups. In addition, LTG-BF1 reduced brain concentrations of TNF-α and TGF-ß with an elevation of EAAT2 and GABA brain contents compared to PTZ and market product groups and ameliorated neuronal damage. In conclusion, LTG-loaded buccal micellar film proved a superior antiepileptic effect in PTZ induced acute epileptic model.

Single step nanospray drying preparation technique of gabapentin-loaded nanoparticles-mediated brain delivery for effective treatment of PTZ-induced seizures.

In the present study, gabapentin (GBP)-loaded chitosan nanosized particles were fabricated applying the nanospray drying technique. Different preparation parameters (spray mesh diameter, chitosan concentration and presence of D-α-Tocopherol polyethylene glycol 1000 succinate (TPGS) were studied while fixing other parameters (spraying rate, inlet temperature and gas flow rate). An optimized formulation with a particle size 107 ± 13 nm was obtained upon spraying 0.1% (w/v) chitosan solution containing 0.05% (w/v) of TPGS utilizing the small nozzle (4 µm spray mesh hole size). Drug entrapment efficiency and yield were as high as 95% and 83%, respectively. A 98.1 ± 6.1% (w/w) cumulative drug release was recorded after 2 h. Confocal laser scanning microscopy showed higher fluorescent dye penetration into brain tissue following intranasal administration of Rhodamine B labeled spray dried chitosan nanoparticles (NPs) as compared to Rhodamine B solution. Pentylenetetrazole (PTZ) was used to induce convulsions in rats through elevating seizure stages, releasing neuroinflammatory mediators and reducing excitatory amino acid transporter 2 (EAAT 2) and γ-aminobutyric acid (GABA) brain contents. Nanospray dried GBP-loaded chitosan NPs reduced seizure score, neuroinflammation; TNF-α and TGF-ß, elevated EAAT 2 and GABA as well as decreased degeneration in pyramidal neurons compared to marketed product Conventin® capsules. Thus, it can be concluded from the aforementioned data that nanospray dried GBP-loaded chitosan NPs could comprise an appropriate treatment of epilepsy.

Promising bioadhesive ofloxacin-loaded polymeric nanoparticles for the treatment of ocular inflammation: formulation and in vivo evaluation.

Our work tackles the combined advantages of both nanotechnology and the bioadhesive gel properties which were utilized to design an ocular drug delivery system that is capable to treat ocular inflammation. Nanoparticles encapsulating an antibiotic drug, ofloxacin, were fabricated using emulsion solvent evaporation technique adopting 23 full factorial design to evaluate the effect of formulation parameters: that is to say, the molecular weight of the polymer (polycaprolactone), amount of Kolliphor P188, and presence of the charge inducer (chitosan hydrochloride) on the measured responses: drug entrapment efficiency (EE%), particle size (PS), polydispersity index (PDI) and zeta potential (ZP). The results show that the optimized LPCL-NP2 formulation (composed of low molecular weight polycaprolactone, 500 mg of Kolliphor P188, 0.25% chitosan hydrochloride, and 50 mg ofloxacin)  displayed a sphere shape with EE%, PS, PDI, and ZP values of 89.73 ± 0.04%, 195.4 ± 13.17 nm, 0.323 ± 0.01, and 55.4 ± 0.66 mV, respectively. DSC study confirmed the amorphous nature of the drug. The optimized nanoparticle formulation was then further incorporated into the following two ocular formulations: gel (LPCL-NP2-G4) and in situ forming gel (LPCL-NP2-ISG4). The penetration of optimized ocular formulations was assessed by confocal laser scanning microscopy. The antimicrobial study was conducted  for the following three ocular formulations: LPCL-NP2 presented as eye drops, LPCL-NP2-G4, and LPCL-NP2-ISG4 as well as the market product using rabbits which were infected in their eyes with Escherichia coli. Results revealed that rabbits treated with LPCL-NP2-ISG4 demonstrated a remarkable antibacterial efficacy and evident low bacterial growth which was additionally assured by the histopathological examination of eye biopsies compared with the other investigated groups. Thus, a novel ofloxacin-loaded nanoparticle formulation based on polycaprolactone is presented in the form of mucoadhesive non-irritating in situ forming ocular gel possessing a superior antibacterial activity. Graphical abstract.

Formulation and Evaluation of Novel Hybridized Nanovesicles for Enhancing Buccal Delivery of Ciclopirox Olamine.

Ciclopirox olamine (CPO) is a topical wide-spectrum antimycotic agent that possesses antifungal, antibacterial and anti-inflammatory activities. Loading CPO into a hybridized vesicular system is expected to enhance its buccal permeation and hence, therapeutic activity, whereas the frequent administration and side effects are reduced. Vesicular systems with high penetration ability were prepared based on cholesterol, Lipoid S45 or Phospholipon 90H, with span 60 while incorporating a penetration enhancer (Labrafac or labrasol) followed by full assessment of their size, entrapment efficiency, and drug release profiles. The optimum formulation, composed of Lipoid S45 and Labrafac, possessed the smallest vesicle size (346.1 nm), highest entrapment efficiency (94.4%), and sustained CPO release pattern, and was characterized for its morphology and thermal properties. This powerful mixture of the penetration enhancers (Lipoid S45 and Labrafac) in the designed hybridized vesicles was thoroughly investigated for their characteristics after being incorporated in bioadhesive gel. Moreover, enhanced antifungal activity was demonstrated either upon testing the designed formulation on agar plates or in vivo upon treating infected rabbits with the proposed formulation. Results suggest that the presented bioadhesive gel incorporating the CPO-loaded vesicles can be a promising delivery system that can offer a prolonged localized antifungal treatment with enhanced therapeutic effect.

Nanotechnology based blended chitosan-pectin hybrid for safe and efficient consolidative antiemetic and neuro-protective effect of meclizine hydrochloride in chemotherapy induced emesis.

The aim of this study was to formulate an easily-administered, safe and effective dosage form loaded with meclizine for treatment of chemotherapy-induced nausea and vomiting (CINV) through the buccal route. CINV comprises bothersome side effects accompanying cytotoxic drugs administration in cancer patients. Meclizine was loaded in chitosan-pectin nanoparticles which were further incorporated within a buccal film. Different formulations were prepared based on a 21.31 full factorial study using Design Expert®8. The optimum formulation possessed favorable characters regarding its particle size (129 nm), entrapment efficiency (90%) and release profile. Moreover, its permeation efficiency through sheep buccal mucosa was assessed via Franz cell diffusion and confocal laser microscopy methods. Enhanced permeation was achieved compared with the free drug form. In-vivo performance was assessed using cyclophosphamide induced emesis. The proposed formulation exerted significant relief of the measured responses (reduced body weight and motor coordination, elevated emesis, anorexia, proinflammatory mediators and neurotransmitters that were also associated with scattered degenerated neurons and glial cells). The developed formulation ameliorated all behavioral, biochemical and histopathological changes induced by cyclophosphamide. The obtained data were promising suggesting that our bioadhesive formulation can offer an auspicious medication for treating distressing symptoms associated with chemotherapy for cancer patients.

Etoricoxib-loaded bio-adhesive hybridized polylactic acid-based nanoparticles as an intra-articular injection for the treatment of osteoarthritis.

Osteoarthritis is a major problem in elder people. Etoricoxib-loaded bio-adhesive hybridized nanoparticles were prepared using polylactic acid (PLA) and chitosan hydrochloride (CS-HCl) in presence of Captex®200 as a liquid oil, polyvinyl alcohol (PVA) and Tween®80 as surfactants. The study aimed to present a new intra-articular treatment of osteoarthritis with anti-inflammatory as well as bone rebuilding effects. Hybridized nanoparticles were fabricated applying the emulsion solvent evaporation technique then assessed for particle size, zeta potential, entrapment efficiency and in-vitro drug release. Furthermore, FT-IR and DSC in addition to morphological examination were done. Results revealed that the formulation composed of PLA:Captex®200 in ratio 1:2 (w/w), 1%w/v Tween®80, 0.3% w/v CS-HCl and 3%w/v PVA possessed the smallest particle size and the most sustained drug release, thus was sorted for further analyses. The selected formulation ability to interact with the negatively charged sodium fluroscein was evaluated to predict its binding with the naturally occurring hyaluronic acid in the knee joint where promising results were obtained. Results showed the cytocompatibility of the formulation when tested using MC3T3-E1 normal bone cell line, enhanced ALP activity and increased calcium ion deposition and binding. Results suggested that the presented formulation can be considered as an innovative approach for osteoarthritis.

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.

Cubic liquid crystalline nanoparticles containing a polysaccharide from Ulva fasciata with potent antihyperlipidaemic activity.

The present study involves the preparation of cubic liquid crystalline nanoparticles (cubsomes) for liver targeting to assess the potential of a formulated bioactive polysaccharide isolated from the hot aqueous extract of Ulva fasciata as an alternative natural agent with anti-hyperlipidaemic activity. Cubosomal nanoparticles were prepared by disrupting the cubic gel phase of the polysaccharide and water in the presence of a surfactant. Different lipid matrices and stabilizers were tested. All the formulations were in the nanosize range and showed sufficient negative charge to inhibit the aggregation of the cubosomes. Drug entrapment efficiencies (EEs%) were determined and in vitro release studies were performed. Transmission electron microscopy (TEM) and differential scanning calorimetry were used to analyze the loaded cubosomal nanoparticles containing glyceryl monostearate (GMO 2.25 g), poloxamer 407 (0.25 g) and 50 mg of the polysaccharide. A preclinical study comparing the cubic liquid crystalline nanoparticles containing polysaccharide to fluvastatin as a reference drug in hyperlipidaemic rats was conducted. The rats treated with the polysaccharide- loaded cubosomes showed significant decreases in total cholesterol (TC), triglycerides (TG) and total lipid (TL) compared to the untreated HL rats. In addition, oxidative stress and antioxidant biomarkers were measured in the HL rats. Compared to the untreated HL rats, the cubosome treated rats showed a significant reduction in malondialdehyde (MDA), whereas insignificant changes were detected in nitric oxide (NO), glutathione (GSH) levels and total antioxidant capacity (TAC). Further, vascular and intercellular adhesion molecules (VCAM, ICAM), and myeloperoxidase were demonstrated. A histopathological examination was conducted to study the alterations in histopathological lesions and to document the biochemical results. In conclusion, this study demonstrates the superiority of using a natural lipid regulator such as polysaccharide loaded cubosomes instead of fluvastatin.

Experimentally designed lyophilized dry emulsion tablets for enhancing the antihyperlipidemic activity of atorvastatin calcium: Preparation, in-vitro evaluation and in-vivo assessment.

This article presents the development of lyophilized orally disintegrating tablets prepared with the dry emulsion technique to enhance the in-vitro dissolution and in-vivo performance of the poorly bioavailable drug atorvastatin calcium (ATV). Tablets were fabricated by freeze-drying o/w emulsions of ATV. The Emulsions were prepared using a matrix former solution (alginate or gelatin, 2 or 4%) containing a sugar alcohol (mannitol) and a collapse protectant (glycine) as the water phase and Labrafac® as the oil phase in the presence of surfactant (synperonic® PE/P 84 or synperonic® F108) under proper homogenization. The influence of formulation parameters on friability of the prepared tablets, disintegration time and in-vitro dissolution of the drug from these tablets were investigated. Results showed the significant influence of the matrix former and emulsifier type on the disintegration time. In-vitro dissolution study revealed the enhanced dissolution rate of ATV from the lyophilized dry emulsion tablets (LDET) compared to the plain drug. DSC and XRD studies of the optimized ATV-loaded LDET proved the presence of the drug in the amorphous form. SEM images showed the intact, porous and non-collapsible structure of the prepared LDET with complete loss of ATV crystallinity. Administration of ATV-loaded LDET to high fat diet-induced hyperlipidemic rats demonstrated a significant decrease (p<0.05) in the serum and tissue levels of the tested parameters compared to the market product used. The obtained results suggest a promising, easy-to-manufacture and effective dosage form for the treatment of hyperlipidemia.

Reconstitutable spray dried ultra-fine dispersion as a robust platform for effective oral delivery of an antihyperlipidemic drug.

The current article highlights the application of spray drying technique to produce an ultra-fine powder encapsulating the antihyperlipidemic drug, atorvastatin calcium (ATV). First, ATV was dissolved in an emulsion formulation, and different carriers (pectin, alginate, chitosan HCl and hydroxypropylmethyl cellulose) in two concentrations (1.5 and 3%) were added. Then, these carrier-containing formulations were subjected to spray drying, whereby ultra-fine ATV-loaded spray dried emulsions were produced (ATV-SDE). The optimum formulation; ATV-SDE7 containing 3% w/w pectin was selected showing an obviously enhanced dissolution profile compared to the other used polymers which could be attributed to its lower ability to swell in acidic medium, resulting in faster drug diffusion into release medium. Thus, ATV-SDE7 was subjected to further characterization including; DSC, XRPD, SEM and flowability properties. In-vivo studies were conducted using high-fat induced hyperlipidemic rats. The optimum formulation depicted normal lipid profile showing significant reduction in the measured parameters at the end of daily oral treatment, compared to ATV marketed tablets and control hyperlipidemic rats confirmed by normal liver sections upon histopathological examination. The superior lipid-lowering activity of ATV-SDE7 was not only due to the enhanced dissolution of ATV but also due to the presence of pectin which is capable of lowering both cholesterol and triglyceride serum levels. Hence, the present study suggests that the formulation strategy employing ultrafine redispersible spray dried emulsion with pectin as a carrier holds a promising approach for the development of a novel dosage form of enhanced antihyperlipidemic effect for ATV.

Development and optimization of self-assembling nanosystem for intra-articular delivery of indomethacin.

Osteoarthritis is a propagated debilitating condition affecting patients' quality of life. Intra-articular injection approach was investigated as a localized treatment strategy providing: site-specific delivery, decreased side effects and, increased patient compliance. A 32 full factorial experimental design was employed to prepare the indomethacin-loaded self-assembling nanosystems (SANS). The surfactant (Poloxamer 407/Tetronic 90R4) ratio and the poly(lactic-co-glycolic acid) (PLGA) concentration significantly affected encapsulation efficiency and drug release (p<0.05). The optimized formula was subjected to modification by addition of different proteoglycans, as a compensatory treatment, to improve its pharmacological properties. The modified SANS, containing glucosamine (150mg), was selected for in-vivo studies as it had a sustained drug release profile and a small particle size (173.90nm). The effect of the optimized SANS, with or without PLGA, was compared with the modified formula containing glucosamine and, with the drug suspension on the arthritic knee joints of rats. It was found that the formulation containing PLGA and glucosamine showed significantly higher reduction in both, knee diameter and TNF-α levels, compared to other groups. Furthermore, all SANS showed histological improvement in the cellularity of the synovial membranes and joints. Our results indicate that SANS containing PLGA and glucosamine is capable of treating arthritic joints.

Design and optimization of gastro-retentive microballoons for enhanced bioavailability of cinnarizine.

This study is focused on the design of gastro-retentive drug delivery system composed of hollow microspheres (microballoons) for the sustained delivery of cinnarizine (CIN). The microballoons (MBs) were prepared by the emulsion solvent diffusion method using cellulose acetate butyrate (CAB) as the hosting polymer and absolute ethanol (ETH) and dichloromethane (DCM) as solvents. A 3(3) full factorial experimental design was adopted to study the effect of different variables and to find an optimum formula with desired properties. Prepared microballoons showed high drug loading capacities and controlled release behaviour. The optimum formulation was chosen on the basis of achieving maximum values for both drug loading capacity and release efficiency as well as having suitable size. The optimized MB (MB-F21) was composed of 200 mg CIN and 400 mg CAB with a DCM/ETH ratio of 2:1. Scanning electron microscopy for the optimum formulation showed a spherical outline with internal porous structure. An in vivo study using human volunteers was performed by determination of CIN concentration in the plasma using the liquid chromatography-mass spectrometry (LC-MS) method. Results proved the superiority of the designed formulation over the market product Stuval® tablets in bioavailability parameters comprising T max as well as area under the plasma CIN concentration-time curve (AUC0-24 h) and AUC0-∞ values. Also, the significantly greater value of mean residence time (MRT) in case of MB-F21 indicates its higher gastric residence time and proves the advantages of micro-multiparticulate dosage forms over conventional one.

Norfloxacin-loaded collagen/chitosan scaffolds for skin reconstruction: Preparation, evaluation and in-vivo wound healing assessment.

Biomaterial scaffolds are versatile tools as drug carrier for treatment of wounds. A series of norfloxacin-loaded scaffolds were synthesized for treatment of wounds by combining collagen with two different types of chitosan using freeze-drying technique. Subsequently, scaffolds were screened in terms of morphology, water absorption and retention capacity, biodegradation, ex-vivo bioadhesive strength, in-vitro drug release biological compatibility, X-ray diffractometry, differential scanning calorimetry as well as in-vivo evaluation. The results indicate that the scaffold mechanical strength is dependent on the type of used chitosan. The prepared scaffolds contained interconnected porous architecture. The scaffolds had high water uptake and retention capacity with extended biodegradation rate. Scaffolds prepared with chitosan HCl showed superior bioadhesive strength compared to those prepared with low molecular weight chitosan. All scaffolds showed almost 100% drug release within 24h. As identified by the terahertz pulsed imaging measurements, there is single scaffold area with the same concentration. After 28 days of wound dressing with selected norfoloxacin-loaded or unloaded collagen/chitosan scaffolds in Albino rats, it was found that the tissue regeneration time was fast compared to non-treated wounds. Furthermore, the drug-loaded scaffolds showed normal structure of an intact epidermal layer as well as the underlying dermis as revealed by histopathological studies. The obtained results suggest that the investigated norfloxacin-loaded collagen/chitosan scaffold is a potential candidate for skin regeneration application.

A trial for the design and optimization of pH-sensitive microparticles for intestinal delivery of cinnarizine.

The aim of this study was to formulate a microparticulate delivery system to deliver cinnarizine (CIN) directly to its site of absorption to overcome its low oral bioavailability. Enteric microparticles were prepared by varying ratios of pH-sensitive polymers (Eudragit L100 and Eudragit S100). A full 3(3) factorial experimental design was adopted to evaluate the effect of variables (CIN concentration as well as Eudragit's concentration) on the tested parameters, namely, particle size (p.s.), drug entrapment efficiency (E.E.), and release efficiency (R.E.). Optimization was done using Design Expert® software to maximize E.E. and R.E. and minimize p.s. The optimized formula was characterized using scanning electron microscopy, differential scanning calorimetry, and X-ray diffractometry. In vivo studies conducted on human volunteers using LC-MS analysis revealed improved bioavailability of CIN-loaded enteric microparticles compared to the market product as detected from calculated pharmacokinetic parameters. This study reveals the usefulness of site-specific delivery of CIN.

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.