Evaluation In Rabbits Research Articles

Limonene-enriched ultra-structural cubosomes to augment ocular delivery of a poorly water soluble anti-fungal drug: Fabrication, characterization, statistical optimization, in vivo corneal uptake and histopathological evaluation in rabbits

The target of this investigation was to obtain the composition of the optimized Fenticonazole nitrate (FCN)-loaded cubosomal formula that can prolong precorneal retention, increase corneal absorption, enhance corneal permeation, and anti-fungal efficacy of FCN. Cubosomes are bi-continuous structural vesicles fabricated using the hot emulsification technique in accordance with a 23-full factorial design. The selected fabrication factors were the concentration of the Lipid phase (X1), glyceryl monooleate: lipid phase stabilizer ratio (X2), and aqueous phase stabilizer types (X3). Whereas, the encapsulation efficiency percent (EE%), Mean particle size (PS), Polydispersity index (PDI), and Zeta potential (ZP) were chosen as measured responses. The numerical optimization criterion of the design expert software was utilized to select the optimized formula (Op) for extra investigations. The Op formula had EE% of 87.94 ± 0.7 %, PS of 249.75 ± 1.48 nm, and ZP of −34.25 ± 0.64 mV. The in vitro release study of the Op formula in comparison with FCN suspension showed a zero-order and controlled kinetic release behavior. Moreover, the results of the pH, refractive index, surface tension, and mucoadhesion study confirmed the superiority and the safety of the Op formula. Further, the ex vivo permeation study demonstrated a significant enhancement in the transcorneal permeation of the Op formula than FCN suspension by 2.69-fold. Besides, the in vivo corneal uptake confirmed the higher permeation of the Op formula in comparison with FCN suspension. Draize test and histopathological examination ensured the in vivo safety and tolerability of the Op formula. Overall, the previous findings ensured the efficacy of cubosomes in enhancing ocular retention, absorption, permeation, and bioavailability of FCN.

Precise Fabrication of Ocular Inserts Using an Innovative Laser-Driven CaliCut Technology: In Vitro and in Vivo Evaluation

Ocular inserts offer distinct advantages, including a preservative-free drug delivery system, the ability to provide tailored drug release, and ease of administration. The present research paper delves into the development of an innovative ocular insert using CaliCut technology. Complementing the hot melt extrusion (HME) process, CaliCut, an advanced technology in ocular insert development, employs precision laser gauging to achieve impeccable cutting of inserts with desired dimensions. Its intelligent control over the stretching process through auto feedback-based belt speed adjustment ensures unparalleled accuracy and consistency in dosage form manufacturing. Dry eye disease (DED) poses a significant challenge to ocular health, necessitating innovative approaches to alleviate its symptoms. In this pursuit, castor oil has emerged as a promising therapeutic agent, offering beneficial effects by increasing the thickness of the lipid layer in the tear film, thus improving tear film stability, and reducing tear evaporation. To harness these advantages, this study focuses on the development and comprehensive characterization of castor oil-based ocular inserts. Additionally, in-vivo irritancy evaluation in rabbits has been undertaken to assess the inserts' safety and biocompatibility. By harnessing the HME and CaliCut techniques in the formulation process, the study demonstrates their instrumental role in facilitating the successful development of ocular inserts.

Development of a Luliconazole Nanoemulsion as a Prospective Ophthalmic Delivery System for the Treatment of Fungal Keratitis: In Vitro and In Vivo Evaluation.

Luliconazole (LCZ), a novel imidazole drug, has broad-spectrum and potential antifungal effects, which makes it a possible cure for fungal keratitis; nevertheless, its medical use in ocular infections is hindered by its poor solubility. The purpose of this study was to design and optimize LCZ nanoemulsion (LCZ-NE) formulations using the central composite design-response surface methodology, and to investigate its potential in improving bioavailability following ocular topical administration. The LCZ-NE formulation was composed of Capryol 90, ethoxylated hydrogenated castor oil, Transcutol® P and water. The shape of LCZ-NE was spherical and uniform, with a droplet size of 18.43 ± 0.05 nm and a low polydispersity index (0.070 ± 0.008). The results of an in vitro release of LCZ study demonstrated that the LCZ-NE released more drug than an LCZ suspension (LCZ-Susp). Increases in the inhibition zone indicated that the in vitro antifungal activity of the LCZ-NE was significantly improved. An ocular irritation evaluation in rabbits showed that the LCZ-NE had a good tolerance in rabbit eyes. Ocular pharmacokinetics analysis revealed improved bioavailability in whole eye tissues that were treated with LCZ-NE, compared with those treated with LCZ-Susp. In conclusion, the optimized LCZ-NE formulation exhibited excellent physicochemical properties, good tolerance, enhanced antifungal activity and bioavailability in eyes. This formulation would be safe, and shows promise in effectively treating ocular fungal infections.

Hyaluronic acid-enriched bilosomes: an approach to enhance ocular delivery of agomelatine via D-optimal design: formulation, in vitro characterization, and in vivo pharmacodynamic evaluation in rabbits

Agomelatine (AGO) is a dual-functional drug. It uses as an antidepressant when orally administrated and antiglaucomic when topically applied to the eye. This study aimed to formulate AGO into bilosomal vesicles for glaucoma treatment, as modern studies pointed out the effect of topical AGO on intraocular pressure for the treatment of glaucoma. A modified ethanol injection technique was used for the fabrication of AGO bilosomes according to a D-optimal design. Phosphatidylcholine (PC) to edge activator (EA) ratio, Hyaluronic acid percentage (HA%), and EA type were utilized as independent variables. The measured responses were percent entrapment efficiency (EE%), particle size (PS), polydispersity index, zeta potential, percentage of drug released after 2 h (Q2h%), and 24 h (Q24h%). The optimal bilosomal formula (OB), with the desirability of 0.814 and the composition of 2:1 PC: EA ratio, 0.26% w/v HA and sodium cholate as EA, was subjected to further in vitro characterizations and in vivo evaluation studies. The OB formula had EE% of 81.81 ± 0.23%, PS of 432.45 ± 0.85 nm, Q2h% of 42.65 ± 0.52%, and Q24h% of 75.14 ± 0.39%. It demonstrated a higher elasticity than their corresponding niosomes with a typical spherical shape of niosomes by using transmission electron microscope. It exhibited acceptable stability over three months. pH and Refractive index measurements together with the histopathological study ensured that the OB formula is safe for the eye and causes no ocular irritation or blurred vision. The OB formula showed superiority in the in vivo pharmacodynamics parameters over the AGO solution, so AGO-loaded bilosome could improve ocular delivery and the bioavailability of agomelatine.

PH Sensitive Pluronic Acid/Agarose-Hydrogels as Controlled Drug Delivery Carriers: Design, Characterization and Toxicity Evaluation.

The objective of this study was to fabricate and evaluate a pH sensitive cross-linked polymeric network through the free radical polymerization technique for the model drug, cyclophosphamide, used in the treatment of non-Hodgkin’s lymphoma. The Hydrogels were prepared using a polymeric blend of agarose, Pluronic acid, glutaraldehyde, and methacrylic acid. The prepared hydrogels were characterized for drug loading (%), swelling pattern, release behavior, the ingredient’s compatibility, structural evaluation, thermal integrity, and toxicity evaluation in rabbits. The new polymer formation was evident from FTIR findings. The percentage loaded into the hydrogels was in the range of 58.65–75.32%. The developed hydrogels showed significant differences in swelling dynamics and drug release behavior in simulated intestinal fluid (SIF) when compared with simulated gastric fluid (SGF). The drug release was persistent and performed in a controlled manner for up to 24 h. A toxicity study was conducted on white albino rabbits. The developed hydrogels did not show any signs of ocular, skin, or oral toxicity; therefore, these hydrogels can be regarded as safe and potential carriers for controlled drug delivery in biomedical applications.

A composite scale to recognize abdominal pain and its variation over time in response to analgesia in rabbits

ObjectiveTo refine a composite scale for pain evaluation in rabbits and evaluate it for pain variations over time. To determine the differences between objective-Centro Animali Non Convenzionali Rabbit Scale (CANCRS) and subjective-Visual Analogue Scale (VAS) in assessing abdominal pain. Study designObservational case–control study. AnimalsA total of 86 rabbits, 47 healthy animals and 39 animals with gastrointestinal stasis syndrome (RGIS), participated in the study; of 39 animals with RGIS, 32 animals participated in the second part of the study. MethodsIn part 1, rabbits underwent pain assessments with VAS and CANCRS. In part 2, the animals underwent four pain assessments with three CANCRS. The first assessment was performed prior to pain management, the others after 30, 60 and 90 minutes. Statistics included Mann–Whitney U test for in-between group comparisons and analysis of variance to assess differences over time. Sensitivity and specificity for each variable of CANCRS were calculated to obtain weighting factors. ResultsCANCRS showed differences between healthy and diseased rabbits (p = 0.0001), and median scores were 5 [interquartile range (IQR): 4–6) and 9 (IQR: 7–11), respectively. VAS showed differences between healthy and diseased rabbits (p = 0.02), and median scores were 4 (IQR: 2–5.35) and 5.3 (IQR: 2.65–6.45), respectively. The cut-off scores for CANCRS and VAS for differentiation between healthy and diseased rabbits were 7 (specificity 89%, sensitivity 79%) and 4.4 (specificity 59%, sensitivity 69%), respectively. Internal validity testing of CANCRS was significant at each time point. Conclusions and clinical relevanceSome variables should be excluded from CANCRS when assessing abdominal pain. CANCRS performed better than VAS, and it detected variations in pain in response to analgesia.

Promising nanogels loaded with usnic acid for oral ulcer treatment: development, characterization, and in vivo evaluation in rabbits

This study aimed to present an effective formulation targeting oral ulcers that will remain in the application site for a longer period, reducing the frequency of administration. As a candidate formulation, usnic acid (UA) was loaded into the optimum nanogels. The characterization studies included physical, rheological, and bioadhesive properties as well as in vitro release and ex vivo studies. The rheological results revealed that the nanogels present pseudoplastic flow behavior. In vitro drug release showed a prolonged pattern. In further, the chosen UA nanogels showed very low percentages of penetration and permeation. F13, which showed the highest release, suitable bioadhesive properties (0.475 ± 0.033 N/cm2) and eligible particle size (250.22 ± 4.11 nm), PDI (0.089 ± 0.052), and zeta potential (20.56 ± 0.330 mV) values were chosen for in vivo experiments. The selected UA nanogels showed effective antimicrobial activity against Bacillus Cereus and great in vivo wound healing properties. The results indicated that suitable UA nanogels with desired properties could be prepared. The therapeutic potential of the nanogels for oral ulcers was assessed using an animal model and the histopathological findings suggested that the optimized formulation is a good choice for oral ulcer treatment. Nonetheless, further research is recommended to support its efficacy by applying pharmacodynamic and pharmacokinetic studies in human individuals.

A new decellularized tendon scaffold for rotator cuff tears \u2013 evaluation in rabbits

BackgroundScaffolds have considerably advanced in recent years. In orthopaedic surgery, scaffolds have been used as grafts in procedures involving tendon and ligament reconstruction. This paper aimed to produce and evaluate decellularized tendon scaffolds (DTSs) from biomechanical, microscopic, macroscopic and in vivo perspectives.MethodsBilateral gastrocnemius muscle tendons from 18 adult New Zealand rabbits were collected. Of these 36 tendons, 11 were used as controls (Group A - control), and 25 were used in the decellularization protocol (Group B - DTS). The groups were subjected to histological, biomechanical and macroscopic analyses, and Group B - DTS was subjected to an additional in vivo evaluation. In the decellularization protocol, we used a combination of aprotinin, ethylenediamine tetraacetic acid (EDTA), sodium dodecyl sulfate (SDS) and t-octyl-phenoxypolyethoxyethanol (Triton X-100) for six days. During this period, the scaffolds were kept at room temperature on an orbital shaker with constant motion.ResultsThe DTSs showed an increased cross-sectional area and inter-fascicular distance and no change in parallelism or matrix organization. The nuclear material was not organized in the DTSs as it was in the control. In the biomechanical analysis, no significant differences were found between the groups after analysing the ultimate tensile load, stiffness, and elongation at the ultimate tensile load. During the in vivo evaluation, mononuclear cell infiltration was noted.ConclusionsThe evaluated decellularization protocol generated a tendon scaffold, maintained the most important biomechanical characteristics and permitted cell infiltration.

HPMC/Carbopol based extended release gastroretentive dosage form of losartan potassium: Formulation and in vivo pharmacokinetic evaluation in rabbits

Novel HPMC/Carbopol based floating gastroretentive (GR) capsules were developed that provided extended release of losartan potassium (LP) in the upper region of gastrointestinal (GI) tract. The in vitro floating properties and drug release of capsules were evaluated in simulated gastric conditions (dissolution medium: 0.1 N HCl; 37 ± 0.5 °C; 100 rpm). In vivo buoyancy studies were performed in rabbits using X-ray radiographic technique. The capsules floated for >12 h in the dissolution medium and provided extended drug release with greater than 90% of the drug released over a period of 12 h. The X-ray images provided an evidence of gastric residence of >8 h. Pharmacokinetic evaluation was performed according to randomized crossover design using rabbits as animal models. The quantification of LP and its active metabolite, E3174 in plasma was performed using a validated HPLC method. Plasma concentration-time curves of LP and E3174 were plotted and pharmacokinetic (PK) parameters including MRT, t1/2, AUC, Cmax, Tmax and ke for both LP and E3174 were obtained. The results were compared with that of market formulation, Cozaar®. Except for the AUC of LP, the novel HPMC/Carbopol capsules had a significant effect on above mentioned PK parameters of LP as well as E3174. The relative bioavailabilities of the LP and E3174 were 126% and 140% respectively.

Veterinary and sanitary evaluation of rabbit as an important reserve of dietary products

The purpose of the study was to perform a comparative veterinary sanitary examination and vetting the rabbit meat of two breeds, depending on the time of year. The subject of the study was 4-month-old male rabbits raised in the private farm, certified with California matured breeds and a Belgian giant (Flanders). According to the principle of analogues, 4 groups of rabbits of 6 heads were formed (2 each in spring-summer and autumn-winter seasons). Before slaughter was determined – the index of abrasion (girth by shoulder blades, divided by the length of the trunk and multiplied by 100%). Carried out anatomical section of carcasses and determined the output of meat. Then they carried out veterinary-sanitary examination by conventional methods. Biochemical studies of meat samples were performed 12 hours after slaughter at storage at 0 – +2 °C. Chemical analysis of the samples included determination of the water content, total protein, ash and macronutrients: Calcium (oxalate method), Phosphorus (photocolorimetric method by A.Yu. Levitsky in AT Usovich's modification). The results were statistically processed using a MS Excel 2003 computer program using a Student's t-test table. The 4-month-old rabbit meat is of California matured breeds and the Belgian giant (flanders) has high, almost equivalent, organoleptic-tasting characteristics. In terms of taste, tenderness, juiciness, color and aroma, the overall average score in the spring-summer and autumn-winter periods, respectively, was: California maturity – 4.7–4.8, and 4.6–4.7; Belgian Giant (Flanders) – 4.8–5.0 and 4.7–4.8 points. The broth of experimental rabbit meat had a delicate, sophisticated aroma and taste, good transparency and received the following points on a 5-point system: California matured and flanders in spring and summer – 5.0, in autumn and winter – 4.8 points. A comparative analysis of the breed characteristics of the studied rabbit identical samples revealed that the Belgian giant (flanders) has the highest moisture-holding capacity in the spring-summer period. The amount of bound water in the muscles of 4-month-old rabbits of the Flanders breed is slightly higher, so it will be more tender and juicy after cooking. The highest slaughter yield was determined in 4-month-old rabbits of the Belgian giant (flanders) and Californians reared in the spring-summer period, respectively – 56.51 ± 0.2% and 0.75 ± 0.63% (P ≤ 0.001). Among the 2 breeds of 4-month-old rabbits, the largest live and slaughter weights reached the rabbits grown in spring and summer (respectively: Belgian giant – 3375 ± 27.0 g and 1912.03 ± 19.4 g; Californians – 2956.5 ± 6.74 g and 1502.48 ± 5.89 g (P ≤ 0.001) .The amount of nutrients in rabbit depends on the breed and time of year. The lowest protein content is found in the meat of 4-month-old rabbits of the California maturing breed period) – 15.47 ± 0.58%, and the highest – in 4-month flanders (spring-summer period) – 23.02 ± 0.78% (P ≤ 0.05). not, however, more meaty and less calorie meat is rabbit california matured breed, regardless of the time of year.

In vivo studies on Mg-1Sc alloy for orthopedic application: A 5-months evaluation in rabbits

The feasibility of Mg-1Sc alloy as orthopedic implant was studied by in vivo implantation into femur shaft of rabbit. The in vivo corrosion rate of Mg-1Sc alloy was 0.60 ± 0.06 mm·y−1. Mg-1Sc alloy could maintain its structural and mechanical integrity for more than 5 months. Compared with Ti6Al4V alloy, Mg-1Sc showed better osteogenesis. The corrosion products were mainly composed of Mg(OH)2, MgCO3·3H2O and calcium phosphate, which would not induce toxic effect. In general, the decent degradation rate in vivo and superior osteogenesis of Mg-1Sc alloy indicate that it may be a promising candidate for biodegradable orthopedic implants.

Cell Phone Radiation Effect on Bone-to-Implant Osseointegration: A Preliminary Histologic Evaluation in Rabbits.

The increased use of cell phones has raised many questions as to whether their use is safe for patients with dental implants. This study aimed to assess the consequences of cell phone-emitted radiation on bone-to-implant osseointegration during the healing phase. Twelve rabbits were grouped into three groups of four. Group 1 (control) was not exposed to electromagnetic radiation; group 2 (test) was exposed for 8 hours/day in speech mode and 16 hours/day in standby mode; and group 3 (test) was exposed for 24 hours continuously in standby mode for 3 months. Forty-eight implants were placed in tibia and femur bone of rabbits, and after 90 days the rabbits were sacrificed and bone surrounding the implant was retrieved. Histopathologic evaluations of the specimens were done using transmitted light microscope. The differences among the three groups were statistically analyzed with analysis of variance (ANOVA) and pairwise comparisons via Fisher's exact test. Significantly less bone-to-implant contact and bone area surrounding implant threads were found in the test groups compared to the control group. There was a significant difference in regular bone formation (P < .001) among the three groups. Implants exposed to cell phone radiation showed more inflammatory reaction when compared to the nonexposed implants, thus indicating that cellular phone overuse could affect the maturation of bone and thus delay osseointegration.

Effect of phage lysin on infection and biofilm formation in rabbit after knee joint prosthesis implantation

Objective To investigate the effect of local injection of phage lyase LysGH15 into rabbits’knee joint on the systemic inflammation, local infection around knee joint prosthesis and biofilm formation on the prosthesis surface after their knee joint prosthesis implantation surgeries. Methods Models of Staphylococcus aureus infection on rabbits’ knee joint prosthesis after prosthesis implantation were built and divided into experimental group for intra-articular injection with lyase and control group for injection with saline into their joint cavity. The phage lysin LysGH15 was synthesized and purified. On the 1st, 2nd and 3rd day after the inoculation with Staphylococcus aureus bacteria into the rabbits’ knee joint cavity of the prosthesis implanted side, 0.5 ml diluted solution of LysGH15 was injected into the knee joint cavity with infection around the prosthesis for the experimental group rabbits and 0.5 ml saline was injected into the corresponding joint cavity for control group rabbits as blank contrast. On the 1st, 3rd, 7th and 14th day, blood samples were collected from their ear vein to make plasma procalcitonin test for evaluation of rabbits’ systemic infection. After the last time for collection of venous blood samples, these rabbits were killed instantly and their knee joints of prosthesis implantation side were dissociated. Tissue around the prosthesis was processed with HE staining to observe and evaluate the local infection and tissue necrosis around the prosthesis. The biofilm formation on the prosthesis surface was evaluated with semi quantitative method after the observation of samples under scanning electron microscope (SEM). Results After the injection of LysGH15 in experimental group, their serum procalcitonin level, which worked as the systemic inflammatory marker, decreased rapidly especially on the 3rd day after lysin injection. Compared with the control group, the infection degree of experimental group significantly decreased. In the experimental group, the infection and necrosis degree of the tissue surrounding the prosthesis were significantly lower in the experimental group than those in the control group. The semi quantitative scores were conducted for these samples and graded to make rank sum test. The difference between the two groups was statistically significant (U=2.4948, P=0.0126). There was a statistically significant difference in the rank sum test between the two groups in the quality of biofilm formation (U=2.2539, P=0.0242). Conclusion Phage lysin LysGH15 can alleviate the rabbits' systemic inflammation caused by Staphylococcus aureus bacteria after their knee joint prosthesis implantation, reduce the extent of damage caused by infection and inflammation to the tissue around the prosthesis, and inhibit the formation of bacterial biofilm on the surface of implanted prosthesis. Key words: Rabbits; Knee joint; Bacteriophages; Biofilms; Prosthesis-related infections; Staphylococcus aureus

Sustained ocular delivery of Dorzolamide-HCl via proniosomal gel formulation: in-vitro characterization, statistical optimization, and in-vivo pharmacodynamic evaluation in rabbits

Glaucoma is the second cause of blindness worldwide. Frequent administration of traditional topical dosage forms may lead to patient incompliance and failure of treatment. Our study aims to formulate proniosomal gel formulations that sustain the release of the water-soluble anti-glaucoma drug Dorzolamide-HCl (Dorz). Proniosomal gel formulations were prepared using coacervation phase separation method according to a 52 full factorial design. The effects of Cholesterol and surfactant (Span 40) amounts (independent variables) on the percentage entrapment efficiency (EE%), particle size (PS), and the percent of drug released after 8 h (Q8h) (dependent variables (DVs)) were investigated. An optimized formulation (OF) was chosen based on maximizing EE% and Q8h and minimizing PS. An intraocular pressure (IOP) pharmacodynamic study was performed in rabbits to evaluate the in-vivo performance of the OF-gel compared to the marketed Trusopt® eye drops. The results showed that the independent variables studied significantly affected EE%, PS, and Q8h. OF was the one containing 60 mg Cholesterol and 540 mg Span 40. It had desirability of 0.885 and its actually measured DVs deviated from the predicted ones by a maximum of 4.8%. The in-vivo pharmacodynamic study showed that OF could result in higher reduction in IOP, significantly sustain that reduction in IOP and increase Dorz bioavailability compared to Trusopt® eye drops. Thus the OF-gel is very promising for being used in glaucoma treatment.

Novel pH responsive supramolecular hydrogels of chitosan hydrochloride and polyoxometalate: In-vitro, in-vivo and preliminary safety evaluation

In the current study, electrostatically-driven pH responsive, supramolecular hydrogels of the trilacunary Wells-Dawson-type 15-tungsto-2-phosphate polyanion (P2W15) and chitosan hydrochloride (ChCl) were prepared, using methacrylic acid as pH responsive agent using benzoyl peroxide (BPO) as initiator. The prepared hydrogels were characterized by FT-IR, SEM, XRD and thermal analyses (TGA-DSC). The swelling and pH based P2W15 release profile of the hydrogels showed maximum swellability and release at pH 7.4. Different mathematical models were applied, showing that P2W15 release followed supercase transport-II mechanism and zero-order kinetics. The cytotoxicity results showed that free and embedded P2W15 exhibited dose-dependent cytotoxicity against cancer cell lines (MCF-7; HeLa) with minimal effects on normal cells (Vero). The developed hydrogels were administered to the rabbits for determining the pharmacokinetic behavior of the polyanion. Moreover, the developed hydrogel system as well as polyanion concentration used were also checked for its oral tolerability and safety evaluation in rabbits. The histopathological studies, serum chemistry (except blood glucose level) and hematological investigations exhibited that administered hydrogel suspension at maximal tolerable dose (4000mg/kg body weight) and polyanion concentration used (20mg) were safe from in-vivo point of view. The developed hydrogels exhibited desirable qualities of a drug delivery system that can be used for the delivery of the embedded polyanion.

Development of novel amisulpride-loaded solid self-nanoemulsifying tablets: preparation and pharmacokinetic evaluation in rabbits

Objective: The current investigation is focused on the formulation and in vivo evaluation of optimized solid self-nanoemulsifying drug delivery systems (S-SNEDDS) of amisulpride (AMS) for improving its oral dissolution and bioavailability.Methods: Liquid SNEDDS (L-SNEDDS) composed of Capryol™ 90 (oil), Cremophor® RH40 (surfactant), and Transcutol® HP (co-surfactant) were transformed to solid systems via physical adsorption onto magnesium aluminometasilicate (Neusilin US2). Micromeretic studies and solid-state characterization of formulated S-SNEDDS were carried out, followed by tableting, tablet evaluation, and pharmacokinetic studies in rabbits.Results: Micromeretic properties and solid-state characterization proved satisfactory flow properties with AMS present in a completely amorphous state. Formulated self-nanoemulsifying tablets revealed significant improvement in AMS dissolution compared with either directly compressed or commercial AMS tablets. In vivo pharmacokinetic study in rabbits emphasized significant improvements in tmax, AUC(0–12), and AUC(0–∞) at p < .05 with 1.26-folds improvement in relative bioavailability from the optimized self-nanoemulsifying tablets compared with the commercial product.Conclusions: S-SNEDDS can be a very useful approach for providing patient acceptable dosage forms with improved oral dissolution and biovailability.

Formulation and development of di-dependent microparticulate system for colon-specific drug delivery.

Colorectal cancer (CRC) is the third most common cancer globally and the second most common cause of cancer-related deaths. Site-specific delivery of drugs leads to an increase in the availability of drugs at the targeted region. The objective of the present investigation was to develop a dually functional microparticulate colon-targeted drug delivery system of meloxicam for potential application in the prophylaxis of colorectal cancer. Chitosan microspheres were prepared by using emulsification-chemical cross-linking technique. Formulation parameters studied include chitosan concentration, drug to polymer ratio, agitation speed, emulsifier concentration, quantity of cross-linking agent and time for cross-linking. In vitro evaluation of microspheres revealed premature release of drug in the upper part of gastrointestinal tract. Since coating of microspheres is difficult to accomplish (with reproducible results), they were compacted to tablets. Enteric coating of tableted microspheres was achieved using Eudragit® S100. In vitro evaluation and SEM studies depict that the microspheres remain intact during compression process. The developed system was further evaluated for in vivo pharmacokinetic and roentgenography studies. In vivo pharmacokinetic evaluation in rabbits reveal that the onset of drug absorption from the coated tableted microspheres (T lag time=4.67±0.58h) was significantly delayed compared to uncoated tableted microspheres. In vivo roentgenographic study revealed that the system remained intact, until it reaches to the colonic region (5h). Thus, from the results of the study, it can be revealed that the developed system could serve as a potential tool for efficient delivery of drug to the colonic region.

In vivo response of AZ31 alloy as biliary stents: a 6 months evaluation in rabbits

Mg-based metallic materials have been making continuing progress as vascular stents. However, the research of Mg-based materials as non-vascular stents is still at its primary stage. AZ31 stents hereby were implanted into the common bile duct of rabbits for 6 months. The results revealed an existence of 93.82 ± 1.36% and 30.89 ± 2.46% of the original volume after 1 and 3 month, respectively. Whole blood tests indicated an inflammation decreasing to normal level after 3 month implantation. A benign host response was observed via H&E staining. Nonuniform corrosion at the two ends of the stents was observed and considered the results of flow or local inflammation. Moreover, the application of Mg-based materials for different stenting treatment were reviewed and compared. Esophagus was hypothesized most destructive, whilst blood vessel and bile duct considered similar and less destructive. Trachea and nasal cavity were thought to be mildest.

Novel non-ionic surfactant proniosomes for transdermal delivery of lacidipine: optimization using 23 factorial design and in vivo evaluation in rabbits

Context: Proniosomes offer a versatile vesicle drug delivery concept with potential for delivery of drugs via transdermal route.Objectives: To develop proniosomal gel using cremophor RH 40 as non-ionic surfactant containing the antihypertensive drug lacidipine for transdermal delivery so as to avoid its extensive first pass metabolism and to improve its permeation through the skin.Materials and methods: Proniosomes containing 1% lacidipine were prepared by the coacervation phase separation method, characterized, and optimized using a 23 full factorial design to define the optimum conditions to produce proniosomes with high entrapment efficiency, minimal vesicle size, and high-percentage release efficiency. The amount of cholesterol (X1), the amount of soya lecithin (X2), and the amount of cremophor RH 40 (X3) were selected as three independent variables.Results and discussion: The system F4 was found to fulfill the maximum requisite of an optimum system because it had minimum vesicle size, maximum EE, maximum release efficiency, and maximum desirability. The optimized system (F4) was then converted to proniosomal gel using carbopol 940 (1% w/w). In vitro permeation through excised rabbit skin study revealed higher flux (6.48 ± 0.45) for lacidipine from the optimized proniosomal gel when compared with the corresponding emulgel (3.04 ± 0.13) mg/cm2/h. The optimized formulation was evaluated for its bioavailability compared with commercial product. Statistical analysis revealed significant increase in AUC (0 − α) 464.17 ± 113.15 ng h/ml compared with 209.02 ± 47.35 ng h/ml for commercial tablet. Skin irritancy and histopathological investigation of rat skin revealed its safety.Conclusions: Cremophor RH 40 proniosomal gel could be considered as very promising nanocarriers for transdermal delivery of lacidipine.

Formulation of mucoadhesive gastric retentive drug delivery using thiolated xyloglucan

Tamarind seed xyloglucan is a polymer reported to possess mucoadhesive property. In the present work, role of cysteine derivative of tamarind seed polysaccharide (thiomer) to enhance the mucoadhesion and its influence on drug permeation has been studied. The xyloglucan was first chemically modified to carboxymethyl derivative which was further converted to thiomer by conjugation with cysteine in presence of a coupling agent, EDAC. The matrix tablets of simvastatin prepared using thiomer demonstrated drug release retardation, increased mucoadhesion force and increased ex vivo permeation, the same were proportional to the increase in the amount of thiomer. The in vivo residence of thiomer placebo was more than 7h in rabbit. Pharmacokinetic evaluation in rabbits indicated higher AUC for the formulation with highest content of thiomer and level ‘A’ correlation could be established from the generated dissolution and bioavailability data.