Recent advances in small molecule drug delivery

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The majority of new drugs, and new drug products, being developed and marketed by the pharmaceutical industry are small molecules. Oral administration remains the most common route of delivering such drugs, typically in the form of immediate-release tablets or capsules. While the immediate-release dosage forms dominate the market today, more specialized and rationalized products incorporating the concepts of drug delivery are being developed to overcome the physicochemical, physiological and pharmacological challenges inherent with the drugs, and to improve the treatment regimens for the patients. Today, these specialized concepts are increasingly being applied to first-generation products and not just products intended for the life cycle management of the franchise.

Introduction

Drug delivery systems that deliver the active drug in a manner that meets the therapeutic need of the patient while eliciting fewer adverse effects are becoming increasingly common. Advanced drug-delivery technologies can improve a product's clinical and commercial value. The past several years have seen tremendous growth in specialized drug-delivery systems that utilize cutting edge technologies such as nanosystems and targeted drug delivery. Advances in areas of biological chemistry and material engineering have enabled scientists to better design drug-delivery systems. The use of nanoparticles in drug delivery is a direct result of the advances made in material engineering in the design and manufacturing of nanoparticles [1, 2, 3, 4, 5]. Targeted drug-delivery is another area that is being actively investigated [6, 7••, 8, 9, 10, 11, 12, 13]. Targeting a drug molecule to the desired site of action offers a tremendous advantage in reducing exposure of other organs and tissues to the drug. This in turn reduces adverse side effects. Also, targeting drug molecules to the site(s) in the gastrointestinal tract where the absorption of the drug is optimum provides an advantage in enhancing the bioavailability of drugs.

Targeting drug molecules to the site of action is becoming a reality, thanks to advances made in biochemistry and, in particular, to the seminal work done on receptor–ligand interactions. Brannon-Peppas has written an excellent review of nanosystems and the targeting of drugs in cancer therapy [14]. In this review, the authors discussed the challenges and possibilities of this drug delivery concept. Polymeric nanosystems have been extensively studied in targeting tumor cells [11, 12, 13, 14•]. Nanoparticles are usually taken up by the reticuloendothelial systems in the body [14]. This uptake is related to properties of the system such as particle size and surface hydrophobicity. Surface modification has been shown to reduce this uptake and hence increase the availability of the anticancer agents at the tumor site [15, 16, 17].

Colonic drug delivery has advanced in the past few years as suggested by the number of publications in pharmaceutical and related journals. Various techniques are being utilized to deliver drugs to the colon either for local effect in the colon or for systemic absorption [18, 19, 20, 21, 22, 23, 24, 25, 26, 27••, 28, 29, 30, 31, 32, 33•]. These include pH-dependent release [20], time-dependent release [23], the use of gum-based polymers [24], a pro-drug approach, and covalent linkage of drug and carrier moieties whose linking bond(s) can only be broken by the bacterial flora of the colon, thus freeing the drug in the colonic region [21, 23, 25, 27••]. This review describes and discusses recent advances in small-molecule drug delivery.

Section snippets

Nanotechnology in drug delivery

In recent years, the interest in sub-micron systems (i.e. nanosystems) in pharmacy has surged. This is, in part, due to the potential advantages these systems provide over more conventional microparticulate systems. Nanosystems can be used in targeted drug delivery to improve the aqueous solubility of poorly soluble drugs [34, 35] and the bioavailability of drugs [17, 36, 37, 38]. The level of interest in these systems and the volume of work being carried out in various research institutions

Targeted drug delivery

Targeting a drug molecule to the site of action is of immense interest to clinicians as it reduces the effect of the drug on other sites while maximizing the therapeutic effect. Targeting drug molecules to the affected cell has been extensively researched in the area of cancer therapy. The driving force for research in this area has mainly been the concern over non-specific and toxic effects of chemotherapeutic agents on normal cells. Yoo et al. [7••] described a self-assembled form of diblock

Colonic drug delivery

Colonic drug delivery has gained popularity in recent years, in part due to its being a potential absorption site for proteins and peptides [19, 33•]. The colon is also potentially a good site for absorption of small molecules that are sensitive to the more enzymatically active and hostile environment of the upper gastrointestinal tract. Colonic delivery has been extensively studied for the delivery of drugs intended for local action in the colon to treat conditions such as irritable bowel

Conclusion

This brief review has discussed some of the recent advances in the delivery of small-molecule drugs. The area of drug delivery continues to grow. The cutting-edge technologies and concepts discussed here promote the safe and effective use of many existing drugs as well as new chemical entities that are filling the drug development pipelines. A concerted effort in this area by drug delivery companies, major pharmaceutical firms, small discovery companies and research institutions will lead to

References and recommended reading

Papers of particular interest, published within the annual period of review, have been highlighted as:

  • • of special interest

  • •• of outstanding interest

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