Current Drug Delivery - Volume 8, Issue 6, 2011

Aim: The goal of this study was to assess the effect of dark chocolate intake on cardiovascular parameters like blood pressure and heart rate values in a normotensive population. Subjects and methods: This is a randomized crosssectional study involving a total of 14,310 adults that were selected from various regions of Jordan. Well-trained pharmacy students interviewed participants in the outpatient settings. Participants reported their weekly intake of dark chocolate that has been further classified into mild (1-2 bars/week), moderate (3-4 bars/week), and high intake (>4 bars/week). For each participant, the systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate were measured three times with (10-15) minute intervals in the sitting position and the resting state. The arterial blood pressure (ABP) was calculated from the measured SBP and DBP values. Results: All measured blood pressure values were significantly decreased for participants who reported higher dark chocolate consumption. Our results showed that heart rate values were not affected by variable intake of dark chocolate. In addition, increasing dark chocolate intake was associated with a significant decrease of blood pressure values in participants irrespective of the family history of hypertension or the age of the individual. However, heart rate values were unaffected. Conclusion: Higher intake of dark chocolate can be associated with lower values of blood pressure, while its effect on heart rate values was not consistent.

Objective: To examine the clinical and histological outcomes following intra-articular injection of an immunomodulatory peptide (CP) during an acute attack of adjuvant induced arthritis in rats. Methods: Arthritis in rats was induced by injecting 0.1mL of Mycobacterium Tuberculosis (MTB; 10mg/ml) intra-dermally at the base of the tail. After the onset of arthritis, affected ankle joints were injected with either 20μl of water, dexamethasone (4mg/ml), cyclosporine (0.38mg; equivalent to 3mg/kg in humans), CP (60mg/ml; 12.5 mg/ml; 6.25 mg/ml; 3.125 mg/ml) or a CP analogue (CPD; 6.25mg/ml). There were a minimum of 5 rats/group and intra-articular injection was given on two separate occasions following the onset of arthritis. Rat weight, paw thickness, paw-width, ankle width and arthritic joint count were measured. Affected joints were X-rayed and joint tissue taken for histology. Results: Rats given dexamethasone and cyclosporine had a significant improvement in clinical outcomes compared to the control group. CP at the highest dose was significantly better compared to the water group and the clinical effects were dose dependent. Histology of the joints showed severe inflammation and destruction in the water treated group with minimal inflammatory effects in the dexamethasone and cyclosporine group. Joints injected with cyclosporine were characterized by extensive fibrosis. The joints from CP treated rats showed mild to moderate inflammation with histological features somewhere between the cyclosporine and water injected groups. Conclusion: This study demonstrates that CP given intra-articularly has antiarthritic effects and raises new possibilities for treatment.

The objective of this study is to utilize the pH sensitivity of modified mesoporous silica nanoparticles (MSN) for oral delivery of insulin. Activated silica nanoparticle was modified first with different densities of 3- Chloropropyltrimethoxysilane (3-CTMS) to load the Chlor group which will bond with the organic functional group contained in 4-hydroxybenzoic acid (4-HBA). The nanoparticles were characterized by FTIR and SEM. Equilibrium swelling studies were carried out in enzyme-free simulated gastric and intestinal fluids (SGF and SIF, respectively). Insulin was entrapped in these nanoparticles and the in vitro release profiles were established separately in both (SGF, pH 1) and (SIF, pH 7.4). The amount of loading of insulin was increased with increasing -COO- densities resulting from the increasing number of 4-HBA groups. In these cases, the biological activity of insulin was retained. These results were used to design and improve protein release behavior from these carriers.

This study investigated the site of release of a model vaccine antigen from plant cells and the corresponding induced immune response. Three plant tissues (leaf, fruit and hairy root) and two formulations (aqueous and lipid) were compared in two mouse trials. A developed technique that enabled detection of antigen release by plant cells determined that antigen release occurred at early sites of the gastrointestinal tract when delivered in leaf material and at later sites when delivered in hairy roots. Lipid formulations delayed antigen release from all plant materials tested. While encapsulation in the plant cell provided some protection of the antigen in the gastrointestinal tract and influenced antigen release, formulation medium was also an important consideration with regard to vaccine delivery and immunogenicity. Systemic immune responses induced from the orally delivered vaccine benefited from late release of antigen in the mouse gastrointestinal tract. The influences to the mucosal immune response induced by these vaccines were too complex to be determined by studies performed here with no clear trend regarding plant tissue site of release or formulation medium. Expression and delivery of the model antigen in plant material prepared in an aqueous formulation provided the optimal systemic and mucosal, antigen-specific immune responses.

The purpose of writing this review on chronotherapeutic drug delivery systems (ChrDDs) is to review the literatures with special focus on ChrDDs and the various dosage forms, techniques that are used to target the circadian rhythms (CR) of various diseases. Many functions of the human body vary considerably in a day. ChrDDs refers to a treatment method in which in vivo drug availability is timed to match circadian rhythms of disease in order to optimize therapeutic outcomes and minimize side effects. Several techniques have been developed but not many dosage forms for all the diseases are available in the market. ChrDDs are gaining importance in the field of pharmaceutical technology as these systems reduce dosing frequency, toxicity and deliver the drug that matches the CR of that particular disease when the symptoms are maximum to worse. Finally, the ultimate benefit goes to the patient due the compliance and convenience of the dosage form. Some diseases that follow circadian rhythms include cardiovascular diseases, asthma, arthritis, ulcers, diabetes etc. ChrDDs in the market were also discussed and the current technologies used to formulate were also stated. These technologies include Contin® , Chronotopic®, Pulsincaps®, Ceform®, Timerx®, Oros®, Codas®, Diffucaps®, Egalet®, Tablet in capsule device, Core-in-cup tablet technology, A coated drug-core tablet matrix, A bi-layered tablet, Multiparticulate-based chronotherapeutic drug delivery systems, Chronoset and Controlled release microchips.

Acne vulgaris is an extremely common condition affecting more than 80-90% of adolescents and young adults. It typically starts in late childhood or early teens, but onset may be delayed in some people well into their 20s and 30s. The incidence rate of acne is roughly the same in males and females but, males tend to have more serious conditions. Common therapies that are used for the treatment of acne include topical, systemic, herbal and combination therapies. This review is an attempt to trace out the causes of acne, to know its treatment options and precautions to be taken to prevent it.

Reactive oxygen species (ROS) and free radicals have been implicated in a number of diseases and disorders, and the skin, for its localization, is exposed to a large number of environmental threats. Free radical scavengers and antioxidants have thus been proposed as protective or therapeutic agents against ROS-mediated injuries. Oral treatment with several antioxidants has been reported to provide skin protection against deleterious effects of ultraviolet radiation. Topical delivery of antioxidants has increasingly gained interest and development, especially by offering better targeting to the upper skin layer. However, the topical delivery of antioxidants for dermal action is a challenging research field since the molecules are, in general, susceptible to degradation. The search for a new delivery system that, simultaneously, preserves the antioxidant stability and enhances its deposition on the skin, opened a new chapter in drug delivery design. Nanocarriers have been successful in enhancing the clinical efficiency of several drugs. More recent approaches in modulating through the skin delivery led to the development of specialized nanoparticulated systems. The first part of this article presents a review of the potential of antioxidants as pharmacological agents in ROS related diseases, with a special focus on oxidative stress implicated skin pathologies: ROS formation and natural protection against ROS toxicity, ROS-mediated skin damage and skin protection by antioxidants. In the second part of this work, we present reported formulation strategies for dermal delivery of antioxidants focusing on the nanoparticulated systems developed in recent years.

The aim of this study was to formulate polyethylene glycol (PEG) based nanoparticulate camptothecin analog for oral administration and to evaluate its pharmacological activity. Camptothecin analog (CA) belongs to topoisomerase-I inhibitor class of compounds with proven antitumor activity but exhibits poor solubility. To enhance solubility and oral bioavailability, a PEG based nanoparticulate formulation was developed using a high pressure homogenization technique. The saturation solubility and dissolution characteristics of the nanoparticulate formulation were investigated and compared with as-is drug formulation to ascertain the impact of particle size on drug dissolution in physiologically relevant dissolution media. Systemic exposure of nanoparticulate formulation were evaluated in Wistar rats for increase in the rate and extent of drug absorption. The antitumor activity of nanoparticulate formulation was evaluated on human tumor xenografts (NCI-H460 cell lines) grown in athymic nude mice and compared with a positive control, Irinotecan Hydrochloride administered intravenously. The saturation solubility and dissolution rate of the nanoparticulate formulation were significantly higher as compared to as-is drug formulation. Pharmacokinetic (PK) studies in Wistar rats indicated significant increase in the rate and extent of absorption for the nanoparticulate formulation. Pharmacological activity of nanoparticles in athymic nude mice with implanted tumors revealed that the tumor inhibition activity was equivalent to Irinotecan Hydrochloride intravenous formulation with comparable safety profile at lower doses. These studies demonstrated the feasibility of developing a safe and efficacious oral formulation for a sparingly soluble camptothecin analog that may provide a viable, patient compliant and, cost effective option for the treatment of solid tumors.

Helicobacter pylori reside in the gastric mucus layer and at the mucus-epithelial cell interface wherein access of antimicrobial drug to the infection site is restricted both from the stomach and from the gastric blood supply. The aim of the present study was to develop pectin or gellan gum blended sodium alginate microspheres in order to eradicate gastric Helicobacter pylori. The percentage drug release and mucoadhesion were decrease on increasing the calcium chloride in the formulation dispersion. Curing time significantly effected encapsulation efficiency and was not affected % drug content, % buoyancy, and particle size and drug release. The efficacy of the optimized formulation was evidenced by absence of amplified bacterial gene in treated stomach tissue of Mongolian gerbils as observed using in polymerase chain reaction. The results demonstrate that the developed formulation of Am has potential to eradicate Helicobacter pylori by targeted and prolonged retention at gastric mucosa.

No literature on the protein stabilization of human serum albumin (HSA) by vacuum foam drying (VFD) has been reported. The purpose of this study was to investigate the effect of sugar-additive systems on the stability of HSA by VFD. For the assessment, HSA was formulated with sucrose and mannitol, respectively, alone or in combination with stabilizers, which were vacuum foam dried and stored at 25°C. Protein content of the resulting dried formulations was analyzed by Lowry method. Fourier-transform infrared spectroscopy (FT-IR) analysis of the HSA secondary structure showed apparent protein structure-stabilizing effects of the amorphous sugar and phosphate combination during the VFD. In particular, sucrose-sodium phosphate monobasic mixture provide an interesting alternative to pure saccharide formulations due to their high glass transition temperatures and their increased ability to maintain a low melting transition temperature in the presence of small amounts of water. Inhibition of the sucrose crystallization in solutions under vacuum resulted in highly amorphous sucrose. Changes in the endothermic melting transition suggested reduced sucrose molecular mobility with increase in the sodium phosphate ratio. The addition of phosphate salts to sugar systems has several interesting features that merit its consideration in formulations to protect dehydrated labile biomaterials. In conclusion, our data suggest that sucrose and phosphate as additives seem to protect HSA during VFD better than lyophilized products and also maintain its stability in the VFD state during storage.

Poor solubility remains a major challenge for pharmaceutical industry, which is now considered to be an area of prime importance in the field of biomedical research. Approximately 40% new molecular entities (NMEs) synthesized in pharmaceutical R&Ds with advanced combinatorial chemistry and computer aided drug designing (CADD) approaches suffer from poor solubility and bioavailability related issues. Apart from these presence of intestinal tight junctional epithelial cells, transporters and enzymatic barriers further reduces the oral absorption of drugs. Implication of the novel lipid based nanocarriers and nanomaterials like dendrimers and carbon nanotubes as a delivery system can effectively enhance the oral bioavailability of drugs by breaching the barriers, and resolve all critics related to solubility and bioavailability. Thus prime objectives of this review are to give in-depth knowledge and critical appraisal on the barriers for poor oral bioavailability of drugs, along with various novel formulation approaches used for bioavailability enhancement such as lipid based formulations, nanosizing techniques, complexation with polymers and nanomaterials like dendrimers, carbon nanotubes, and penetration enhancers. Also it gives a brief account on in vitro, in vivo screening methods used for assessment of oral bioavailability, and regulatory considerations for the approval.