Current research interest can be categorized into four main areas:
I. Drug Formulations Development:
The main research interest of this group is focused on the development of pharmaceutical preparations for newly approved medications based on new approaches of pharmaceutical nanotechnology to: develop unique delivery systems for variety of medications implementing new approaches such as proniosomes, niosomes,...etc.
Our research interests focus on the development of nano/microparticle formulations for controlled delivery of therapeutic molecules including proteins and peptides. The research team is studying various approaches and mechanisms for enhancing drug incorporation and controlled release in formulation of drug delivery systems. The primary objective of the research projects is to achieve targeted drug delivery into the brain, skin and eye using novel biodegradable polymeric systems.
II. Pharmaceutical Biotechnology:
Our research team is currently working on investigation of newly drug delivery systems for treatment of cancer (colorectal cancer and lymphoma).
A. Colorectal cancer:
King Abdulaziz City for Science and Technology
Grant Number: KACST (AT-25-23)
The incidence of colon cancer has increased over the last 25 years worldwide and in Saudi Arabia. Each year, there are about one million new case of colorectal cancer. It is considered the second leading cause of cancer-related death for men and women.
Colorectal cancer is the second leading cause of cancer-related death for men and women. Each year there are about one million new case of colorectal cancer. Its incidence has increased over the last 25 years. The early detection and diagnosis and the use of more effective less toxic systems would tremendously improve the efficacy of therapy. The objective of the work in this filed is to prepare an optimum colonic drug delivery system and evaluating the efficiency of the system for delivering diagnostic elements like 5-aminolevulinic acid (5-ALA) directly to the colon providing a novel, simple, and non-invasive method that can be easily used for routine screening for colon cancer. In addition, this system will be utilized in providing a useful way of targeting anticancer drugs like 5-fluorouracil (5-FU) to the colon with the potential of much more effective and less toxic colon cancer treatment.
B. Production and site-specific delivery of bleomycin for treatment of cancer:
Center of Excellence in Biotechnology Research
Grant Number: (CEBR-06)
The incidence of cancer has increased over the last 25 years in Saudi Arabia. Bleomycin (BLM) is a glycopeptide antibiotic that is used in treatment of variety of human neoplasms, particularly lymphomas, squamous cell carcinoma and germ-cell tumors. Cytotoxicity of BLM once inside the cell is very high, but limited due to the poor uptake into the cells, which was shown to be receptor mediated endocytosis. Bleomycin has been identified as the most effective anti-cancer drug among many tested when delivered intracellularly by electroporation. Bleomycin is currently produced by fermentation. Production of antibiotic anticancer is considered the most important useful application of the current pharmaceutical biotechnology.
Generally antibiotics are produced by batch fermentation using free cell cultures. To enhance the productivity and improve the economics, much attention has been paid on the improvement of the culture employed in the antibiotics production. The large scale production technology is lacking in Saudi Arabia and in most of the developing countries.
The aim of this project is to transfer and implement fermentation technology to KSA and utilize it in the production of BLM in economical quantities and design novel drug delivery systems that ensure superior therapeutic efficacy and much less toxic profile than the currently marketed products of BLM.
The production of BLM will start by traditional fermentation techniques of a producer strain of streptomycetes. The physiological parameters will be optimized to attain productivity. Scaling up will be carried out to re-optimize the production conditions of 50-100 liters. Meanwhile the microorganism will be subjected to gene amplification to enhance the production of BLM. An attempt to enhance the productivity via the immobilizations of microbial cells into hydrogel microspheres will be considered in the study.
Various particulate and viscular drug delivery systems will be utilized in enhancing BLM intracellular uptake by cancer cells. Controlling the vesicular size to the nano-scale would have high potential in improving the efficacy of BLM. These systems will be targeted for the local treatment of colon cancer topically by encapsulation into hard gelatin capsule coated with a combined pH-dependent polymer. In addition, it will be designed as new injectable form with high specificity toward leukemia.
Establishment of fermentation unit capable for designing a no-how for the economical production of BLM in KSA. Introducing novel drug delivery system(s) for superior therapeutic efficacy and less toxicity profile.
C. Optimization of Oral Delivery for DNA Based Vaccines:
Center of Excellence in Biotechnology Research
Grant Number: (CEBR2-05)
The use of DNA-based vaccines attracted much attention recently. In addition to their ability to elicit both humoral and cellular immune responses, they are very stable, safe and cost effective in manufacturing and storage. Intramuscular administration was initially considered as the primary route for DNA vaccine delivery. Because of the limited and variable potency after injection, there is always a need to improve the immunogenicity of the vaccines and/or to explore alternative delivery systems.
Oral immunization provides a promising alternative. This route can allow for massive immunization without the need for specially trained personnel to deliver the vaccine and does not require the strict sterility of parenteral products. Orally administered DNA vaccine is taken up by the M-cells which are the entrance port to the Peyer`s patches where antigen presentation can take place. This will stimulate B- and T-cells and thus, stimulate mucosal immune response before leaving the Peyer`s patches through the thoracic duct and reaching the systemic circulation. Oral vaccination can thus provide both mucosal and systemic immunization providing double protection. However, the development of effective oral DNA vaccine is hindered by many complications such as gastrointestinal degradation and poor uptake by the Peyer`s patches.
DNA vaccine plasmid gWIZ/HBs HBs in which expression of the HBs antigen is driven by a strong CMV modified promoter will be used. An incremental innovative approach to optimize the HBs cDNA expression delivered to the target cells will also be developed. This approach consists in genetically engineering the plamid to tune the HBs cDNA sequence to the human codon-usage preference.
Accordingly the objective of this work will be to optimize nanoemulsion formulation for enhancing the oral bioavailability of drugs especially those having poor permeability problem and/or subject to presystemic disposition via efflux and metabolism.
To achieve this objective effect of various formulation parameters such as composition, charge, droplet size and the presence of antinucleant on the oral bioavailability of model drug(s) from nanoemulsion and SNEDDS. The model drug(s) will be selected from those suffering poor bioavailability due to permeability problems or due to extensive presystemic disposition like paclitaxel (anticancer), carbamazepine (antiepileptic) or atenolol (antihypertensive). The nanoemulsion will be formulated and characterized with respect to size, zeta potential, dispersability, solubilization capacity and drug release. Optimum formulation will be tested for improved drug delivery potential. These evaluations will employ intestinal absorption measurement in vitro, in situ and in vivo.
III. Nanotechnology and Drug Delivery:
National Research Funding Program (Nano Technology Research)
Grant Number: (08-Nan307-2)
Optimization of nanoemulsion and self nanoemulsifying drug delivery systems for oral drug delivery:
The oral drug delivery route offers many advantages over other routes of administration. It eliminates the need for strict sterility and trained persons required for production and administration of injections. However, poor oral bioavailability made it difficult for many valuable drugs such as insulin and most anticancer agents to be delivered via the oral route. Poor oral bioavailability can be attributed to different reasons including enzymatic degradation of drug, poor permeability, poor solubility and dissolution, intestinal efflux and pre-systemic metabolism in the intestine and liver. The use of nanoemulsions to overcome these problems is being investigated extensively. They can be used as O/W or W/O liquids or as self nanoemulsifying drug delivery systems (SNEDDS).
Nanoemulsions can improve oral bioavailability by many mechanisms. These include protection of drugs (such as peptides and proteins) from degradation by the metabolizing enzymes and enhancing the solubility and dissolution of lipophilic drugs. In addition, they can increase the transcellular and/or paracellular gastrointestinal membrane permeability, they may reduce hepatic metabolism of drugs that have significant first pass effect by increasing the trans-lymphatic drug transport lipophilic drugs or they can inhibit the P-glycoprotein efflux pump, which is responsible for secretion of the absorbed molecules entering the enterocytes back to the gastrointestinal lumen. All these effects were found dependent the composition and characteristics of the emulsion and were unpredictable.
The objective of this proposed research is to develop and deliver DNA vaccines via a route of administration other than injection. Oral delivery system is chosen for this proposed research aiming to improve patient compliances and increase immunogenicity. Hepatitis B vaccine was chosen in the proposed research as a model DNA vaccine. Genetic engineering of an existing Hepatitis B DNA vaccine plasmid will be one of the aims of this work to optimize the antigen expression in the target cells by tuning the HBs cDNA sequence the human codon-usage preference. Different carrier systems including liposomes, niosomes and micro and nano suspensions will be formulated for the delivery of DNA vaccine. The different formulations will be characterized, optimized and compared in vitro. The most promising formulations with high stability and good physical characteristics will be subjected to in vivo study in small and higher animals. The efficacy and safety of the different vaccine formulations will be assessed by measuring the antibody and cellular responces post-immunization. Based on these immunological studies the successful formulation that will show high immunogenicity are planned to be evaluated in human volunteers aiming to produce market formulations for oral delivery of hepatitis B vaccine.
Different carrier systems including liposomes, niosomes and micro and nano suspensions will be formulated as the carrier system for the delivery of hepatitis B vaccine as a model DNA based vaccine. This work is expected to lead to potential applications for international patents regarding optimizing genetically engineered Hepatitis B vector (in agreement with Alveron) and optimizing carrier systems for oral delivery of a model DNA based vaccine. The formulations are planned to be subjected to evaluation on experimental animals and human volunteers aiming to produce market formulations for oral delivery of the DNA based vaccines with improved patient compliances and increased immunogenicity.
The expected results could lead to the rapid development of a potent and cost effective oral DNA vaccine for hepatitis B. The development of such vaccine will be a breakthrough achievement and will greatly benefit the countries with intermediate or high endemicity of hepatitis B infection such as in the Middle East area including Saudi Arabia where this infection is a major health problem.
IV. Advanced Polymer Sciences:
The center of Excellence for Research in Engineering Materials
Grant Number: (430-CEREM-03)
Design and Synthesis of a Novel Crown Ether-Crosslinked Chitosan for Removal of Toxic Metal Ions (M+n) from Wastewater: An Industrial Application:
The water supply in Saudi Arabia has increased dramatically from 1.75 billion m3 in 1975 to 22.93 billion m3 in 1992. In Saudi Arabia, the total amount of wastewater available is around 1.32 million m3/d. In the near future, these amounts of industrial wastewater are of several hundred times-folds larger. The industrial areas of Saudi Arabia generate some of industrial wastewater which is discharged directly into the sea water without extensive treatment. The four main components of wastes in the Saudi Arabia industries are large-volume cooling water, lower volume but high-to-low strength process wastes from refineries and petrochemicals, and sanitary wastes. In addition, future expansion in the refineries and secondary industries in the areas will result in a greater pollution of the seawater and thus affect the productivity and quality of the seawater and environments surrounding the industrial areas.
An unfortunate consequence of industrialization is the generation and the release of toxic waste products which are polluting our environment. Heavy metal contamination of various water resources is of great concern because of the toxic effects of heavy metals on human beings and other animals and plants, even at very low concentrations, and were listed as priority pollutants by the United States Environmental Protection Agency.
Addressing these problems calls out for a tremendous amount of research to be conducted to identify robust new methods of purifying water at lower cost and with less energy consumption, while at the same time minimizing the use of chemicals and impact on the environment. Advanced techniques of the science and technology are being developed to improve the disinfection and decontamination of water, as well as efforts to increase water supplies through the safe re-use of wastewater and efficient desalination of sea and brackish water. Adsorption has been proved to be an excellent way to treat industrial waste effluents, offering significant advantages like the low-cost, availability, profitability, easy of operation and efficiency.
In recent years, biosorption using materials of biological origin as the adsorbents for heavy metal removal has attracted more interest, largely due to the unique properties of these biomaterials being environmentally benign, low cost, effective at low metal concentrations, and easily reusable. Among these biomaterials, chitosan, a derivative from N-deacetylation of chitin (a naturally abundant polysaccharide from crustacean and fungal biomass) has particularly attracted attention because of its capability to chemically or physically adsorb various heavy metal ions.
Chitosan has received considerable interests for heavy metals removal due to its excellent metal-binding capacities and low cost as compared to the activated carbon. Chitosan can be recycled by releasing bound metals with an acid wash leaving the metal waste more highly concentrated in a greatly reduced volume. After rinsing with water, chitosan is available for immediate re-use. However, chitosan usually displayed poor acidic resistance and would gradually dissolve in a solution of pH 4 or less, which is considered a major drawback of chitosan as most industrial wastewater containing heavy metals are almost acidic and eventually, will limit the use of the chitosan, as low-cost recyclable sorpent, in decontamination of industrial wastewater.
One goal of this research is to investigate and plan to overcome the above mentioned dilemma through the synthesis of new and novel chitosan derivatives, crown ether crosslinked chitosan. This crown ether crosslinked chitosan is a water insoluble derivative either in a basic or in an acidic medium and still exhibits an excellent heavy metal adsorption capacity. In addition, the crown ethers, which contain a hydrophobic ring of ethylenic groups surrounding a hydrophilic cavity of ether oxygen atoms, possess the greatest affinities for the alkali and alkaline earth cations. The crown ether crosslinked chitosan proposed to be synthesized will be characterized using analytical and instrumental methods. Also, its adsorptive properties of industrial heavy metals either in basic or acidic industrial waste water will be characterized for large scale usefulness in decontamination of industrial waste water to be re-used in our daily life as in agriculture and in industries that require large amounts of water as in cooling process of nuclear plants or even to be re-used for human being.