Iranian Journal of Pharmaceutical Sciences

In recent decades, most of researchers in pharmaceutical preparations have focused increasingly on new formulations that control the site and amount of drug delivery. Mucoadhesive dosage forms are available for systemic or local treatment. The mucoadhesive dosage forms are introduced in various forms such as tablets, gels, ointments, patches and polymeric films. For buccal wound and injury the polymeric films may be preferred due to flexibility, comfort, longer residence time, protection of the wound surface and promotion of the wound healing. Most of dentists apply phenytoin sodium suspension as a gargle for promoting healing in dental surgery. In this study, a novel phenytoin sodium mucoadhesive film consisting of two layers of polymeric film was prepared by solvent casting method. One layer contained various ratios of carbapol 934, NaCMC, HPMC and a constant proportion of PEG 400 as plasticizer. The other layer contained cellulose acetate phethalate which acts as water resistant for unidirectional release. The film's mechanical properties such as swelling, in vitro adhesion/drug release and residence time by using human volunteers were measured.among different polymers the HPMC/Na CMC/CP 934 were selected and thirteen formulations (F1-F13) were prepared. The best formulation in physical properties were F1, F6, F8, F9 and F13. F8 had the highest and F1 had the lowest swelling index, and all formulations had high adhesive strength. Formulation F6 had a fast release pattern during the first 30 mins, but F8 had the highest amount of release in 3 hours. F1 had the lowest amount of release during 3 hours. F1 had the longest residence time while F8 and F9 showed the shortest residence time accompanied with detachment. From the current study, one can conclude that the buccoudhesive film of F13 containing 60% HPMC, 20% NaCMC and 20% CP had zero order models of drug release and possesses suitable swelling profile, good adhesion strength, appropriate residence time and produced no irritation. Optimum ratio for the mucoadhesive polymeric film composed of Carbopol/Na CMC/HPMC, was 20/30/40 (wt/wt/wt) in terms of flexibility, comfort, long residence time, swelling, and bioadhesive force.

Survivin, an inhibitor of apoptosis protein is highly expressed in most cancers and considered as an attractive target for cancer antisense therapy. To vectorize antisense molecules, cationic nanoliposomes are generally used; however, their complexes are too instable, during shelf-life and upon exposure to blood components and extracellular matrix, to be used in-vivo. The present study aimed to develop fresh and lyophilized formulations of antisense/DOTAP nanoliposomes with different helper lipids and compare their shelflife and biologic stabilities and their transfection activities in tumor cell lines. DOTAP nanoliposomes in combination with different helper lipids were prepared in HEPES buffer (20 mM, pH=7.4) by thin-layer hydration followed by thermobarrel extrusion and PTFE membrane filter sterilization. Nanoliposomes were characterized regarding their particle size distribution, final lipid recovery and physical stability. Following antisense loading by direct addition through electrostatic attraction, the degree of complexation was determined by ethidium bromide displacement assay. To stabilize the formulations, they were freezedried with 10% sucrose. The potential of the lyophilized and fresh formulations of
FITC-labeled antisense to transfect different cell lines (SK-BR-3, MCF-7) was studied by flow cytometry. Fresh nanoliposomes of different formulations had a size in range of 50-100 nm. The degree of complex formation with antisense was determined almost 70-80% (N/P ~ 2) which decreased as incubated with either PBS or complete medium and heparin sulfate. Their average sizes significantly changed after preservation for few days at 4 °C.Lyophilization process compromised the particle size distribution and antisense loading efficiency of different formulations except for DOTAP/DOPE (1:1 mole ratio) which did
not change significantly. Both fresh and lyophilized formulations exhibited the highest transfection activity at comparable levels especially in SK-BR-3 cells. As a conclusion, lyophilization process could promote stability and preserve transfection activity of the antisense complexes of DOTAP/DOPE (1:1) nanoliposomes.

Polyphenolics form a major part of the dietary antioxidant capacity of fruits and vegetables have been identified as chemopreventive or anticancer agents. Hydroxychalcones are polyphenols abundantly distributed throughout the plant kingdom and are compounds with two aromatic rings (benzene or phenol) and an unsaturated side chain. In the present study, effect of phloretin (apple major flavonoid), 4-hydroxychalcone and 4'-hydroxychalcone were investigated against acetaminophen-induced acute liver damage. The study was designed as multiple dose pre- and post-treatments. Mice were administrated
acetaminophen (1g/kg and 640 mg/kg for mortality and acute toxicity experiments, respectively). Mortality rate, serum transaminases (SGOT and SGPT) and histological examination were applied. Acetaminophen produced 100% mortality at the dose of 1 g/kg in mice, while pre-treatment and post-treatment (i.p., twice daily for 48 hrs) of animals with phloretin and 4-hydroxychalcone (50 mg/kg) and 4'-hydroxychalcone (25 mg/kg) significantly reduced the mortality rate. Acetaminophen produced acute toxicity at the dose of 640 mg/kg in mice, while pre- and post-treatments of animals with phloretin and hydroxychalcones significantly lowered the rise in SGOT and SGPT. Liver sections collected for histological examination showed cellular changes including centrilobular necrosis, extensive portal inflammation, and micro and macro vesicular structures in the acetaminophen group. These cellular changes were reduced following treatment of mice with Phloretin and hydroxychalcones. Taken collectively, from the results of this study it may be suggested that phloretin and hydroxychalcones have hepatoprotective activity against acetaminophen liver injury in mice.

Caffeine, an adenosine A1, A2A, and A2B receptor antagonist, is frequently used as an adjuvant analgesic in combination with non steroidal anti-inflammatory drugs or opioids. The aim of this study was to evaluate the effects of caffeine on preventing the development of morphine tolerance and analgesia in mice. In this study, different groups of mice received morphine (30 mg/kg) + saline (10 ml/kg), or morphine (30 mg/kg) + caffeine (10, 15, 25, 50, 75, or 100 mg/kg) i.p. once a day for four days. Tolerance was assessed by administration of morphine (9 mg/kg) and using hot-plate test on the fifth day. Analgesic effects of caffeine also were evaluated alone or in combination with different doses of morphine. It was found that pretreatment with caffeine (75, 100 mg/kg) decreased the degree of morphine tolerance significantly (p<0.01). Combination of caffeine (10, 50 mg/kg) with morphine (3, 6, 9 mg/kg) caused a significant decrease in morphine analgesic effect (p<0.01). But, in high doses of caffeine (100 mg/kg) the analgesic effect of morphine increased significantly (p<0.01). This effect was inhibited by atropine (5 mg/kg, SC). These effects can be related to different mechanisms of caffeine in different doses and the effects of caffeine to the release of acetylcholine.

The present study was carried out to determine the hypoglycemic activity of the methanolic extract and solvent fractions (n-hexane and ethyl acetate) of Ruellia tuberosa in normal and alloxan-induced diabetic rabbits. Optimum dose of R. tuberosa for hypoglycemic activity was determined by oral administration of the methanolic extract (ME) to normal and diabetic rabbits. Diabetes was induced by intra-peritoneal injection of alloxan monohydrate (150 mg/kg). Hypoglycemic effect of n-hexane (HF) and ethyl acetate (EF) fractions was evaluated at a dose of 150 and 100 mg/kg b.w., respectively, in normal and diabetic rabbits. Administration of the optimum dose (500 mg/kg b.w.) of R. tuberosa to normal and diabetic rabbits showed significant blood glucose lowering effect. EaF (100 mg/kg) showed the highest anti-diabetic activity with 28.64±0.28% decrease in blood glucose, while HF (150 mg/kg) showed moderate anti-diabetic activity and lowered the blood glucose level around 15.17±0.58%. The results were compared with the standard drug tolbutamide (100 mg/kg). Phytochemical investigation of EF and HF indicated flavonoids and triterpenoids in the extracts, respectively. Antioxidant activity was evaluated by DPPH method and the amount of total phenols was determined by Folin-Ciocalteu method. ME extract and its fractions showed the antioxidant activity in the order of EF>ME>WF>HF. The results were in agreement with the folkloric use of R. tuberosa in the treatment of diabetes and related complications.

Biosurfactants are surface-active compounds produced by microorganisms. In this study, we collected 60 inguinal area and ear canal samples from cows, sheep, and goats (each, 10 animals) and screened for biosurfactant-producing bacteria. We also determined the genera of culturing strains. Fifty six hemolytic bacterial strains (27, 22 and 7, from cows, sheep and goats, respectively) were isolated. Oil spreading
test and bioemulsifying activities were measured for all isolates. The cows’ samples had higher population of positive strains than other animals, so that 5 isolates from inguinal area and 4 from ear canal samples (16.1%) were positive for all tests. For sheep, the numbers were 6 and one (12.5%) while for goats one and two (5.3%), respectively. Totally, 19 isolates (33.9%) were positive for all examinations out of
them 12 were gram positives. The microorganisms isolated in this study could well be sources of novel biosurfactants. Further investigation into the composition of the biosurfactants and phylogenetic determination of biosurfactant producing bacteria is suggested.

The effect of prepared Ayurvedic formulation was evaluated on excision and incision wound models in rats. The wound-healing activity was assessed by the rate of period of epithelialization and skin-breaking strength. Histological study of the granulation tissue was carried out to know the extent of collagen formation in the wound tissue. The Ayurvedic formulation prepared was then promoted for woundhealing
activity in two wound models. The treated animals showed a significant reduction in the wound area and faster rate of epithialisation. In an incision wound model, formulation treated animals demonstrated a significant skin-breaking strength. Histological studies of the tissue obtained from the formulation treated group revealed that the activity was more significant in this group. Our present study reveals that the Ayurvedic formulation posses a potent wound healing activity, which could be a good choice of remedy for wound healing but less potent than standard nitrofurazone.