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Personal care products and pharmaceuticals (ppcp)
Interaction of membrane transporters with ppcps
Solvo's offer
Applications of ABC transporter assays
How to benefit from our assays?
Solvo: the transporter company
Partnering with Solvo
Cooperation / service business models on drug transporters


Ecosystem change is effected by human activities primarily via three routes: habitat fragmentation, alteration of community structure and chemical pollution. Previously, the impact of chemical pollution has focused almost exclusively on the conventional priority pollutants. SOLVO is developing assay systems and diagnostic tools based on the interaction of various chemical compounds with ABC and Efflux transporters. These tools will serve as early and rapid (High throughput) indications of the environmental toxicity profile of the compounds.



Personal care products and pharmaceuticals (ppcp)



Figure 1: Effects of pollution
(Source: http://www.claybennett.com)


A very important, diverse group of bioactive chemicals receiving comparatively little attention as potential environmental pollutants includes the pharmaceuticals and active ingredients in personal care products (PPCPs), both human and veterinary, including not just prescription drugs and biologics, but also diagnostic agents, "nutraceuticals", fragrances, sun-screen agents and numerous others.

Even though some PPCPs are extremely persistent and introduced to the environment in very high quantities and perhaps have already gained ubiquity worldwide, others could act as if they were persistent, simply because their continual infusion into the aquatic environment serves to sustain perpetual life-cycle exposures for aquatic organisms.





Figure 2: Destroying the environment
(Birds I view: Noel O. Pama, Sr,
Source: http://www.ncca.gov.ph)

In contrast to agrochemicals, the majority of the pharmaceuticals are discharged into the environment on a continual basis via domestic/industrial sewage systems and wet-weather run-off.
Some studies show that many of the compounds survive biodegradation, eventually being discharged into receiving waters; moreover, metabolic conjugates can even be converted back to their free parent forms. These chemicals, together with their synthetic precursors and transformation products, are continually released into the environment in enormous quantities as a result of their manufacture, use (via excretion, mainly in urine and feces), and disposal of unused/unwanted drugs and those that have expired, both directly into the domestic sewage system and via dumping to inappropriate landfills.
A striking reality is that pharmaceuticals have the potential for ubiquitous direct release into the environment worldwide-anywhere that humans live or visit. Even areas considered relatively untouched (e.g. national parks) are subject to pharmaceutical exposures. Other possible sources include disposal of pharmaceuticals into domestic sewage systems.
Although most pharmaceuticals are designed to target specific metabolic pathways in humans and domestic animals, they can have numerous often unknown effects on metabolic systems of nontarget organisms, especially invertebrates.


Personal care products differ from pharmaceuticals in that large amounts can be directly introduced to the environment. These products can be released directly into recreational waters or volatilized into the air. In contrast to pharmaceuticals, less is known about the effects of this broad and diverse class of chemicals on nontarget organisms, especially aquatic organisms. Most of these personal care products are used as the active ingredients or preservatives in cosmetics, toiletries, or fragrances. Almost no attention has been given to the end of life of personal care products i.e. fate after disposa - the focus has traditionally been on the effects from intended use on human health.

  • Fragrances are ubiquitous, persistent, bioaccumulative pollutants that are sometimes highly toxic; amino musk transformation products are toxicologically significant.
  • Parabens are one of the most widely used suites of antimicrobial preservatives in cosmetics, toiletries, pharmaceuticals and food. Although the acute toxicity of these compounds is very low, some studies reported that these compounds display weak estrogenic activity in several assays. Although the risk from dermal application in humans is unknown, the probable continual introduction of these benzoates into sewage treatment systems and directly to recreational waters from the skin leads to the question of risk to aquatic organisms.
  • A wide array of disinfectants/antiseptics is used in large amounts not just by hospitals, but also by households and livestock breeders. Many of these compounds directly or indirectly find their way into receiving waters As with all antibiotics in the environment, this could lead to development of resistance and change in the microbial community structure (diversity).
  • Sunscreen agents (SSAs) are frequently found in fish from small lakes used for recreational swimming (). SSAs was also detected in human breast milk (). This shows the potential for dermal absorption and bioconcentration in aquatic species.
  • Nutraceuticals are a rapidly growing commercial class of bioactive compounds, usually botanicals, intended as supplements to the diet. Normally, naturally occurring compounds would not pose an ecologic risk, but this statement ignores that the concentrations of these compounds in effluents could be higher than they are in the environment in which they occur naturally. Moreover, many of these substances/mixtures come only from isolated parts of the worlds, and their use/dispersal in other parts of the world would essentially make them anthropogenic. This promotes exposure to organisms that normally would never occur.
  • In addition, scientists have been warning consumers that the use of detergents and their disposal in our rivers, lakes and oceans are creating a problem for these delicate ecosystems. With the rapid increase of human populations, it is becoming an urgent problem.


Interaction of membrane transporters with ppcps

ABC transporter proteins are mostly known from their role in Multidrug resistance (MDR). However, the physiological function of ABC transporters is protection of cells from xenobiotics, a phenomenom also referred to as Multixenobiotic Resistance (MXR). This function of ABC transporters is not well explored, though studies exist on aquatic organisms (Smital et al., 2004).

Inhibition or saturation of MXR in aquatic organisms is a cause for concern. Aquatic organisms are continually exposed to pollutants present in water. When ABC transporters, and hence, the natural defense system of these organisms is saturated or inhibited, accumulation of toxins might occur. This might lead to dramatic changes in aquatic wildlife but also to introduction and accumulation of certain pollutants in the food chain.
Little is known about the interaction of human ABC transporters with common pollutants like polycyclic aromatic hydrocarbons (PAHs), heavy metals, chloroalkanes, phthalates or agrochemicals.

Solvo's offer

SOLVO is developing assay systems and diagnostic tools based on the interaction of various chemical compounds with ABC and Efflux transporters. These tools will serve as early and rapid (High throughput) indications of the environmental toxicity profile of the compounds.
SOLVO Biotechnology provides four different solutions for ABC (xenobiotic) and uptake transporter assays to be used in drug discovery:
  • Membrane Preparations - to be used for ATPase Assay and Vesicular Transport Assay (direct uptake) measurements
  • Fee-For-Service Screening
  • Sublicense for the Calcein Assay
  • Custom-Made Expression and Screening Systems







Applications of ABC transporter assays



Figure 5: The human cells
(Source: http://www.biocenter.hu)

The three major applications of ABC Transporter assays are:
  1. Predicting the penetration of test compounds through the pharmacological barriers (blood-brain barrier, intestinal mucosa, kidney, liver etc.) = in vitro predictive ADME,
  2. Predicting the penetration of intracellularly active cytostatics into the cancer cells,
  3. Testing of functional effect of MDR modulators.



How to benefit from our assays?

SOLVO's mainstream products can be used for:
  1. Expression of a wide array of human ABC transporters (MDR1, MDR2/3, MRP1, MRP2, MRP3, MRP4, MRP5, MRP6, MXR, BSEP and others) and rodent (rat, mouse) transporters in various expression systems (e.g. baculovirus-based insect cell)
  2. Functional characterization of proteins (ATPase, transport and binding data)
  3. Identification of new drug targets on ABC transporters.
  4. Development of various cell lines expressing a range of pharmacologically relevant uptake transporter proteins

Our unique technology platform is characterized by the following attributes:
  • Flexible collaboration models for Client focused Services and Reagent sales
  • Cost-efficiency
  • Reliability, as only one transporter is expressed in each individual reagent at one time
  • Easy-to-use methodology with detailed HT protocols available for all reagents (including all insect and mammalian membrane assays)



Solvo: the transporter company

A wide array of ABC transporter assays and cell lines expressing various uptake transporter proteins assays are available from SOLVO. SOLVO is constantly developing new assays, for additional ABC and for other transporters as well.
The patented Calcein Assay, ATPase Assay and some Vesicular transport assays are optimized for high-throughput screening on 96 well plates and widely used by pharmaceutical companies. SOLVO provides full technology transfer for in-house use as well as fee-for-service screening.

Field/segment Application Worldwide status Solvo's position
In vitro Pharmaco-Kinetics In vitro data to help predict in vivo PK Accepted for Pgp, and some uptaketransporters still in exploratory phase for others Leader in the transporter technology
Formulation To predict the effect of formulation agents (excipients, etc) on drug absorption) Exploratory One of the pioneers
FMCG applications To predict the absorption of valuable compounds as well as toxicants/irritants Exploratory One of the pioneers
Diagnostics In vitro assessment of multidrug transporter status of patients - theranostics Exploratory Leader
Drug discovery & development
Novel therapeutic approaches utilizing transporters as targets to treat MDR diseases and CV disorders Slowly moving Just moved with a novel approach
Environmental sciences Early and rapid indicators of the environmental toxicity profile of chemical compounds. Exploratory Leader


Partnering with Solvo


Partnering is a key part of our research and business strategy. Our group is committed to collaborating with others, developing long-term partnerships that leverage each company's strengths, and bringing significant advances to researchers worldwide.

SOLVO is interested in collaborations which may take many forms:
  • Products- co-development, product acquisitions and/or co-promotion/co-marketing arrangements 
  • Strategic partnerships that build on complementary capabilities to develop comprehensive Technology Platforms
  • Broad based research collaborations, including alternative discovery initiatives and new collaborative model
  • In-licensing compounds, technologies or other intellectual property from Academic and Industrial Research laboratories and out-licensing our technology from the R&D pipeline
  • Academic liaisons



Cooperation / service business models on drug transporters

1. Fee For Service Screening - Outsourced Screening of Compounds

Deliverables:
Full Project Report on:

  • relevant transporter - compound interactions;
  • affinity of the compounds to the respective transporters;
  • substrate nature of the compounds;

Consultancy services:
  • Formulation Guidelines;
  • Development Guidelines;
  • Suggested Next Steps

2. Reagent Sale: Perform Screening In-House

Deliverables:
Various Assay Reagent Products (cells, membranes and reagents including detailed protocols)

Calcein Assay Sublicence

Technical Support
  • On site training and assistance for the set-up of a screening lab;
  • Online e-mail and Telephone Technical Support

3. MultiDrugQuant™ Diagnostics

  • Kit Sales
  • Co-Development for new indications

4. Joint Individual Development Projects on Assay Systems / Diagnostics / Therapeutics

  • SOLVO - Company Research Contract or Co-Development



 

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Last updated: January 14, 2008
This page contains information about following topics: Pgp, P-gp, MDR1, ABCB1, P-glycoprotein, MRP1, ABCC2, MRP2, ABCC2, cMOAT, MRP3, ABCC3, cMOAT-2, MRP4, ABCC4, MOATB, MRP5, ABCC6, BCRP, MXR, ABCG2, BSEP, ABCB11, ratBsep, mouse bsep, mouse bcrp, mouse mxr, rat Mdr, rat Mrp2, MDR3, NTCP, SLC10A1, rat Ntcp, OATP1B1, OATP-C, OATP2, SLCO1B1, OATP1B3, OATP8, SLCO1B3, OATP2B1, OATP-B, SLCO2B1, rat Oatp1a1, Oatp1, rat Oatp1a4, Oatp2, rat Oatp1b2, Oatp4, PEPT1, SLC15A1, PEPT2, SLC15B2membrane transporter,calcein assay kit,screening,MDR1,MRP1,MRP2,MRP3,MRP4,MXR,BSEP,blood-brain barrier, haematology, MultiDrugQuant, solid tumor, clinical trial, leukemia, absorption.