Pharmaceutical Nanotechnology (v.5, #1)

Meet Our Editorial Board Member by Qiang Peng (1-1).

Preface by Ijeoma F. Uchegbu (2-2).

Background: Cancer chemotherapy is accompanied with administration of highly potent cytotoxic agents in doses that can result in non-specific drug toxicity and side effects. Chemotherapeutic agents possess limitations such as lack of water solubility, high volume of distribution, poor bioavailability, narrow therapeutic indices, multi-drug resistance, etc. that raise serious matters of concern regarding drug's pharmaceutical and clinical aspects. However, application of nanoparticles in delivery of anti-cancer agents has been a popular approach to address these concerns. Poly (lactide-co-glycolide) (PLGA), a biocompatible/biodegradable FDA-approved polymer has been widely used as drug carrier to enhance pharmaceutical/therapeutic properties of anticancer agents, prolonging their circulation time, targeting cancer tissues or protecting the drug from rapid elimination/premature degradation. This favourably modifies drug's pharmacokinetics and pharmacodynamics.

Objective: This paper provides a general perspective on how association of docetaxel to PLGA nanoparticles potentially modifies pharmacokinetics and biodistribution profile of the anticancer agent.

Method: A comprehensive literature search has been conducted and dedicated to compile most relevant and up-to-date material about pharmacokinetic consequences of PLGA nanoparticles in docetaxel drug delivery.

Results: A set of determinants are considered to be influential on biodistribution and fate of docetaxel and PLGA nanoparticles. These are attributed to physicochemical properties of PLGA polymer, docetaxel, nanoparticle, and the set of events imposed to the nanoparticles by the host body.

Conclusion: Association of PLGA nanoparticles and docetaxel has demonstrated to modify the drug's pharmacokinetic and biodistribution profile.

Influencing Factors of the Pharmacokinetic Characters on Nanopharmaceutics by Xiwei Ji, Wei Lu, Kehua Wu, William C. Cho (24-31).
Background: Nano-pharmaceutics have been actively studied for the encapsulation and targeted delivery of drugs to improve the treatment strategies for various diseases. Because of the size, nano-pharmaceutics show some special characteristics of pharmacokinetics (PK). There are quite a number of studies focusing on the efficacy and toxicity of nano-pharmaceutics. However, only few of them investigated PK.

Method: Literature search was conducted to summarize recent studies on PK of nano-pharmaceutics.

Result: Both the efficacy and toxicity of nano-pharmaceutics are associated with their absorption, distribution, metabolism and elimination (ADME). Absorption mainly affects bioavailability, while distribution gears with target delivery. Both absorption and distribution play important roles in the efficacy of nano-pharmaceutics. Metabolism and elimination are the major influencing factors for the toxicity of nano-pharmaceutics. PK models and physiologically-based PK models can be powerful tools to analyze and predict the in vivo behavior of nano-pharmaceutics based on experimental data.

Conclusion: Further research will be needed to investigate the underlying mechanism between the ADME processes of nano-pharmaceutics and their efficacy and toxicity.

Transdermal Lipid Nanocarriers: A Potential Delivery System for Lornoxicam by Sandipan Dasgupta, Subhabrata Ray, Sanjay Dey, Paulami Pal, Bhaskar Mazumder (32-43).
Background: Lornoxicam, is a NSAID of the oxicam class. Its short duration of action owing to rapid elimination and gastrointestinal side effects limits its usefulness when administered orally.

Objective: The primary objective of the proposed work is to develop suitable lipid nanocarriers for transdermal delivery of Lornoxicam with increased drug residence time at local site of inflamation and in systemic circulation, overcoming undesired gastrointestinal side effects.

Method: Lornoxicam loaded lipid nanocarriers like solid lipid nanocarriers (SLN), nano-structured lipid carriers (NLC) & nanoemulsions (NE) were prepared by high-speed homogenization technique.

Result: The particle size, zeta potential, and polydispersity index as obtained, were in the range of 140- 193 nm, -22 to -32 mV, and 0.354-0.301 for SLN formulations and 146-201 nm, -23 to -30 mV, and 0.355-0.354 for NLC formulations respectively. Characterization of stable NE revealed that globule size, zeta potential and polydispersity index were within the range of 138 to 195 nm, -26.1±0.123 mV and 0.195 ± 1.231 respectively. It was also observed that entrapment efficacy and drug loading improved as the lipid concentration was increased. The results obtained from the in vitro permeation study and in vivo anti-inflammatory study showed controlled drug permeation, increased bioavailability, longer retention and better therapeutic potential of Lornoxicam after transdermal application of lipid nanoparticles as compared to conventional gel.

Conclusion: It can be concluded that the developed lipid nanoparticle loaded gel was found to be a suitable drug delivery carrier for transdermal delivery of Lornoxicam to increase the residence time of drug in systemic circulation and to combat the gastrointestinal side effects.

Background: Development of pH-responsive nanoparticles capable of rapid degradation in the acidic environments in the endosomes and lysosomes of tumor tissues but relatively more stable in the physiological pH (pH 7.4) is desirable.

Objective: To show that the number of methoxy groups on the benzene ring of benzaldehyde bisacrylate acetal crosslinkers should affect the rate of hydrolysis of the crosslinkers and in vitro availability of the drug loaded into the nanoparticles.

Method: Three pH-sensitive acetal crosslinkers were synthesized and characterized by 1H NMR, 13C NMR, FT-IR and high resolution mass spectroscopy (HR-MS). The nanoparticles were fabricated by free-radical dispersion polymerization method. Hydrolysis studies were carried out on the crosslinkers and nanoparticles; drug release studies were done on docetaxel-loaded nanoparticles at pH 5.0 and pH 7.4. The statisitical experimental design was randomized complete block design followed by analyses of variance with F-test of significance. Pairwise comparison test was used to locate specific differences among parameters of the crosslinkers and the nanopaticles.

Results: Scanning electron micrographs showed the formation of spherical particles. Particle size analysis showed that the nanoparticles are within nanosize range with negative zeta potential. Data showed that the rate of hydrolysis and drug release were faster at pH 5.0 compared to pH 7.4. Hydrolysis and drug release studies were dependent on the structure of the acetals: Di(2-methacryloyloxyethoxy)- [2,4,6-trimethoxyphenyl] methane crosslinker showed the fastest rate of hydrolysis, followed by di(2- methacryloyloxyethoxy)-[2,4-dimethoxyphe-nyl] methane and di(2-methacryloyloxyethoxy)-[4-methoxyphenyl] methane.

Conclusion: The pH-responsive nanoparticles are suitable for the delivery of bioactive agents, especially anticancer drugs.

Background: Application of magnetic nanoparticles as a drug delivery system has attracted great attention in the cancer therapy, interests in the pH and thermo-sensitive polymers have been increased exponentially in biomedicine.

Objective: (N-isopropylacrylamide)-ethylene glycol dimethacrylate copolymer was coated on the surface of Fe3O4 magnetic nanoparticles and utilized as a pH and temperature responsive nanocarrier for encapsulation and delivery of doxorubicin, as an anti-cancer drug.

Method: First, Fe3O4 nanoparticles were prepared through the chemical co-precipitation method and then coated by poly (N-isopropylacrylamide)-ethylene glycol dimethacrylate copolymer shell. The synthesized nanocarrier were later used as a drug carrier for the DOX drug delivery.

Results: Nanocarriers were characterized by a number of techniques i.e. scanning electron microscopy (SEM), dynamic light scattering (DLS(X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), Thermo gravimetric analysis (TGA) and vibrating sample magnetometer (VSM). The effects of pH and temperature on the drug release rate were evaluated. The obtained result revealed that doxorubicin release rate of the polymer is temperature and pH dependent, which are desirable properties for a selective delivery system. At the end of 72 h, only 15% of doxorubicin had been released in pH 7.4 conditions comparing to that of 58% in pH 5.8 acidic conditions at 40°C.

Conclusion: This project improves the delivery of anti-cancer drug. The preparation of this nanocarrier was simple and fast and the prepared sorbent is biocompatible.