Based on my research experience over past 3 decades on drug transporters, this review focuses on: i) importance of molecular biopharmaceutics, ii) recent progress in identification and characterization of drug transporters and iii) illustrative cases of successful drug delivery to target organs via transporters. With the help of great progress in key pharmaceutical technologies, we are now entering a new era of drug delivery. Although several drug transporters have been utilized as novel delivery systems, transport mechanisms for the majority of drugs are still unknown. Therefore, we have to identify all the participants in order to establish the potential utilities of this approach. We require an efficient screening system to pick appropriate transporter (s) that can be used for delivery and also for target and/or lead discovery. Another aspect that demands careful consideration may be pharmacokinetic drug-drug interaction at the transporter and the effects of single-nucleotide polymorphisms (SNPs) of drug transporters.
To develop an effective dry-powder inhalation system for insulin absorption, via the alveoli, a nanocomposite particle system was prepared using the Mechanofusion® dry-powder composition system. The nanocomposite particles were an ordered mixture of coarse carrier lactose (c.a. 60 μm in diameter) adsorbed with poly (lactic-co-glycolic acid) (PLGA) nanospheres (c.a. 250nm in diameter). The flowability and in vitro inhalation property of the resultant PLGA composite was improved as compared to untreated PLGA nanosphere powder. The inhalation properties of the PLGA nanosphere composite were determined by the Mechanofusion® operating conditions. Slow speed operation (270 rpm) of the composing rotor could not combine the PLGA nanospheres with lactose. A rotor speed higher than 370 rpm was required to enable proper composition. However, applying a high share force during for composition process, (i.e., setting a narrow clearance), deteriorated the inhalation property and the redispersibility of the resultant composite particle into water to reconstruct the original nanosphere. About 65% of the intratracheally administered composite particle was deposited deeply into the lung of rat. The nanocomposite particle dry powder inhalation system using insulin loaded PLGA nanospheres significantly improved the absorption of insulin and prolonged the pharmacological action compared to insulin solutions administered intravenously or intratracheally.