PROFESSOR VINESS PILLAY & DR. YAHYA E. CHOONARA Department of Pharmacy and Pharmacology at the University of the Witwatersrand NRF/DST South African Research Chair: Pharmaceutical Biomaterials and Polymer-Engineered Drug Delivery Technologies Director: Wits Advanced Drug Delivery Platform Institutional Director: Wits Hub of the MRC/Wits National Medical Devices Innovation Platform Email: viness.pillay@wits.ac.za Wits Advanced Drug Delivery Wits Advanced Drug Delivery Platform Platform… …. . Innovation in Motion Innovation in Motion
In a nutshell: � Drug carriers � Modification of drug release and ADME properties � Drug targeting Common types of drug delivery systems: � Conventional dosage forms � Modified release systems � Gastroretentive systems � Microstructures � Nano-Enabled systems Wits Advanced Drug Delivery Wits Advanced Drug Delivery Platform Platform… ….Innovation in Motion .Innovation in Motion
� Nanostructures cannot be considered superior as they do form part of larger systems/devices � Is it a case where Microtechnology has just gotten smaller…so what is the big deal?... � Microtechnology is also very small and has shrunk to the point that it is now nano anyway… � Many times Nanotechnology is built upon Microtechnology via modified microfabrication � This may imply Nanotechnology is not yet mature and should remain as Nanoscience. There is plenty good Nanoscience, but not yet much in the way of viable Nanotechnology � Our limited understanding of the complexities indicate that molecular modeling simulations and chemometrics would win in predictive power and assisting in rational systems design � Describing nanotechnology based on merely size is pointless since the usefulness of drug delivery systems are not based only on size � Nevertheless, it is the largest potential growth sector of the pharmaceutical industry and is spurring researchers to take that leap in enabling the generation of innovative nanomedicines � An exceptionally large economic force set to reach an annual global market worth USD1 trillion Wits Advanced Drug Delivery Wits Advanced Drug Delivery Platform Platform… ….Innovation in Motion .Innovation in Motion
� For a freely soluble drug, S is not critical: large C s � large k � large dC/dt dC DS ( ) = S − C C � For a poorly soluble drug, k is small � dC/dt is highly responsive to S dt Vh For e.g. 5cm 3 – about 1.7cm per side – of material divided 24 times will produce 1nm cubes and spread in a single layer could cover the field at Soccer City Wits Advanced Drug Delivery Wits Advanced Drug Delivery Platform Platform… ….Innovation in Motion .Innovation in Motion
� Nanomedicines may be less favored due to safety concerns with pulmonary disposition leading to inflammation or even tumor formation � Globally, including SA legislation is under development on the handling of hazards/exposure and there is a need for risk assessment and risk management of nanomaterials � Size, shape and morphology play a key role in determining safety � Little attention has been placed on requiring approval from the US Food and Drug Administration (FDA) – grey area � The main challenge with current methods are low drug-loading capacity and poor ability to control the size distribution � Pharma industry is slow to utilize the new systems with components that are not G enerally R egarded A s S afe (GRAS) � The future depends on the ability of scale-up production by nano-manufacturing � Re-engineering of clinical research through translational research is required to advance basic discoveries to clinical studies Wits Advanced Drug Delivery Wits Advanced Drug Delivery Platform Platform… ….Innovation in Motion .Innovation in Motion
� Speaks of the ‘control of matter’ that can be used to design systems to serve specific therapeutic needs � The ‘nanocrystal story’ demonstrates how a simple technique can improve the performance of poorly water-soluble drugs � Essentially the physicochemical principles in terms of interactions with surfaces, diffusion behavior and hydrodynamics are modified � This overcomes anatomical and physiological barriers to provide efficacious drug delivery � Characterized by high surface-area to mass ratio and stabilized against agglomeration � Typically prepared by molecular deposition/complexation (“bottom up”) or attrition of larger materials (“top down”) � Range in size from 80-1000nm for many pharmaceutical applications Wits Advanced Drug Delivery Wits Advanced Drug Delivery Platform Platform… ….Innovation in Motion .Innovation in Motion
� According to the US National Institute of Health’s Nanomedicine Roadmap Initiative, nanotech will offer innovative medical intervention for diagnosis, prevention and treatment of diseases � The secret is to manipulate supramolecular structures to produce programmed nanodevices � Nano-manufacturing processes that can churn out nano drug delivery systems for e.g. soft gelatin capsules at the nano-scale will revolutionize drug therapy. � Development of nanodevices for both diagnosis and therapy (theragnosis) using the same device hold great promise in personalized medicine Wits Advanced Drug Delivery Wits Advanced Drug Delivery Platform Platform… ….Innovation in Motion .Innovation in Motion
Nanocrystals � ����������� Nanoparticles � Nanocapsules � ������������ ���������� Nanofibers � Nanoliposomes � Nanotubes � �������� Nanogels � ��� Dendrimers � �������� Nanosuspensions � Nanomicelles � ��������� ���������� ������������ ��������������� ���������� Wits Advanced Drug Delivery Wits Advanced Drug Delivery Platform Platform… ….Innovation in Motion .Innovation in Motion
� Spray freezing into liquid (SFL) � Emulsification � Precipitation with a compressed fluid antisolvent (PCA) � Rapid expansion from a liquefied-gas solution (RESS) � Evaporative precipitation into aqueous solution (EPAS) � High-pressure homogenization � Microfluidization � High-energy wet milling Wits Advanced Drug Delivery Wits Advanced Drug Delivery Platform Platform… ….Innovation in Motion .Innovation in Motion
Professor William Pardridge, M.D. Professor William Pardridge, M.D. UCLA, Brain Research Institute, Los Angeles, CA, USA (Drug Discovery Today, UCLA, Brain Research Institute, Los Angeles, CA, USA (Drug Discovery Today, 12, 54-61, 2007) 12, 54-61, 2007) “Considering the potential size of the global CNS pharmaceutical market, and considering that so “Considering the potential size of the global CNS pharmaceutical market, and considering that so few drugs cross the BBB, one would expect that the development of BBB drug delivery technologies would few drugs cross the BBB, one would expect that the development of BBB drug delivery technologies would be a high priority in the pharmaceutical industry and in the academic sciences. be a high priority in the pharmaceutical industry and in the academic sciences. In fact, there is not a single medium or large pharmaceutical company in the world today that has a BBB- In fact, there is not a single medium or large pharmaceutical company in the world today that has a BBB- drug-targeting technology program. drug-targeting technology program. Even if Big Pharma wanted to change this situation, there would be no staff to hire because there are so few Even if Big Pharma wanted to change this situation, there would be no staff to hire because there are so few BBB scientists being trained in academia. BBB scientists being trained in academia. In the USA, there is not a single academic neuroscience program that has any emphasis on BBB drug In the USA, there is not a single academic neuroscience program that has any emphasis on BBB drug targeting technology. targeting technology. One routinely reads summaries of workshops in either the USA or Europe that are devoted to various CNS One routinely reads summaries of workshops in either the USA or Europe that are devoted to various CNS diseases such as Alzheimer’s and Parkinson's disease, brain cancer or stroke, and the issue of BBB drug diseases such as Alzheimer’s and Parkinson's disease, brain cancer or stroke, and the issue of BBB drug delivery is not even mentioned” delivery is not even mentioned” � Drug delivery to the brain is limited by the BBB � Drug delivery to the brain is limited by the BBB � <2% of small molecules cross the BBB (400Da; lipophilic) � <2% of small molecules cross the BBB (400Da; lipophilic) � 100% of large molecules do not cross the BBB � 100% of large molecules do not cross the BBB � Rely on specialized transport mechanisms at the BBB interface � Rely on specialized transport mechanisms at the BBB interface � CNS conditions are escalating in the young and old......need breakthroughs now!!! � CNS conditions are escalating in the young and old......need breakthroughs now!!! Wits Advanced Drug Delivery Wits Advanced Drug Delivery Platform Platform… ….Innovation in Motion .Innovation in Motion
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