Pharmaceutics

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Open AccessEditorial

Liposomes in Drug Delivery: How It All Happened

by Gregory Gregoriadis

Pharmaceutics 2016, 8(2), 19; https://doi.org/10.3390/pharmaceutics8020019 - 24 May 2016

Cited by 61 | Viewed by 6823

Effective delivery of drugs via liposomes in the treatment or prevention of disease is the aim of numerous researchers worldwide.[...] Full article

(This article belongs to the Special Issue Liposome Technologies 2015)

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Open AccessReview

Current Trends in Development of Liposomes for Targeting Bacterial Biofilms

by Zora Rukavina and Željka Vanić

Pharmaceutics 2016, 8(2), 18; https://doi.org/10.3390/pharmaceutics8020018 - 24 May 2016

Cited by 138 | Viewed by 11525

Abstract

Biofilm targeting represents a great challenge for effective antimicrobial therapy. Increased biofilm resistance, even with the elevated concentrations of very potent antimicrobial agents, often leads to failed therapeutic outcome. Application of biocompatible nanomicrobials, particularly liposomally-associated nanomicrobials, presents a promising approach for improved drug [...] Read more.

Biofilm targeting represents a great challenge for effective antimicrobial therapy. Increased biofilm resistance, even with the elevated concentrations of very potent antimicrobial agents, often leads to failed therapeutic outcome. Application of biocompatible nanomicrobials, particularly liposomally-associated nanomicrobials, presents a promising approach for improved drug delivery to bacterial cells and biofilms. Versatile manipulations of liposomal physicochemical properties, such as the bilayer composition, membrane fluidity, size, surface charge and coating, enable development of liposomes with desired pharmacokinetic and pharmacodynamic profiles. This review attempts to provide an unbiased overview of investigations of liposomes destined to treat bacterial biofilms. Different strategies including the recent advancements in liposomal design aiming at eradication of existing biofilms and prevention of biofilm formation, as well as respective limitations, are discussed in more details. Full article

(This article belongs to the Special Issue Liposome Technologies 2015)

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Open AccessReview

Nanomilling of Drugs for Bioavailability Enhancement: A Holistic Formulation-Process Perspective

by Meng Li, Mohammad Azad, Rajesh Davé and Ecevit Bilgili

Pharmaceutics 2016, 8(2), 17; https://doi.org/10.3390/pharmaceutics8020017 - 20 May 2016

Cited by 168 | Viewed by 14251

Abstract

Preparation of drug nanoparticles via wet media milling (nanomilling) is a very versatile drug delivery platform and is suitable for oral, injectable, inhalable, and buccal applications. Wet media milling followed by various drying processes has become a well-established and proven formulation approach especially [...] Read more.

Preparation of drug nanoparticles via wet media milling (nanomilling) is a very versatile drug delivery platform and is suitable for oral, injectable, inhalable, and buccal applications. Wet media milling followed by various drying processes has become a well-established and proven formulation approach especially for bioavailability enhancement of poorly water-soluble drugs. It has several advantages such as organic solvent-free processing, tunable and relatively high drug loading, and applicability to a multitude of poorly water-soluble drugs. Although the physical stability of the wet-milled suspensions (nanosuspensions) has attracted a lot of attention, fundamental understanding of the process has been lacking until recently. The objective of this review paper is to present fundamental insights from available published literature while summarizing the recent advances and highlighting the gap areas that have not received adequate attention. First, stabilization by conventionally used polymers/surfactants and novel stabilizers is reviewed. Then, a fundamental understanding of the process parameters, with a focus on wet stirred media milling, is revealed based on microhydrodynamic models. This review is expected to bring a holistic formulation-process perspective to the nanomilling process and pave the way for robust process development scale-up. Finally, challenges are indicated with a view to shedding light on future opportunities. Full article

(This article belongs to the Special Issue Nanocrystals)

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Open AccessReview

Stabilizing Agents for Drug Nanocrystals: Effect on Bioavailability

by Annika Tuomela, Jouni Hirvonen and Leena Peltonen

Pharmaceutics 2016, 8(2), 16; https://doi.org/10.3390/pharmaceutics8020016 - 20 May 2016

Cited by 193 | Viewed by 17379

Abstract

Drug nanocrystals are a versatile option for drug delivery purposes, and while the number of poorly soluble drug materials is all the time increasing, more research in this area is performed. Drug nanocrystals have a simple structure—a solid drug core is surrounded by [...] Read more.

Drug nanocrystals are a versatile option for drug delivery purposes, and while the number of poorly soluble drug materials is all the time increasing, more research in this area is performed. Drug nanocrystals have a simple structure—a solid drug core is surrounded by a layer of stabilizing agent. However, despite the considerably simple structure, the selection of an appropriate stabilizer for a certain drug can be challenging. Mostly, the stabilizer selection is based purely on the requirement of physical stability, e.g., maintaining the nanosized particle size as long as possible after the formation of drug nanocrystals. However, it is also worth taking into account that stabilizer can affect the bioavailability in the final formulation via interactions with cells and cell layers. In addition, formation of nanocrystals is only one process step, and for the final formulation, more excipients are often added to the composition. The role of the stabilizers in the final formulation can be more than only stabilizing the nanocrystal particle size. A good example is the stabilizer’s role as cryoprotectant during freeze drying. In this review, the stabilizing effect, role of stabilizers in final nanocrystalline formulations, challenges in reaching in vitro–in vivo correlation with nanocrystalline products, and stabilizers’ effect on higher bioavailability are discussed. Full article

(This article belongs to the Special Issue Nanocrystals)

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Open AccessReview

Challenges, Solutions, and Quality Metrics of Personal Genome Assembly in Advancing Precision Medicine

by Wenming Xiao, Leihong Wu, Gokhan Yavas, Vahan Simonyan, Baitang Ning and Huixiao Hong

Pharmaceutics 2016, 8(2), 15; https://doi.org/10.3390/pharmaceutics8020015 - 22 Apr 2016

Cited by 13 | Viewed by 10442

Abstract

Even though each of us shares more than 99% of the DNA sequences in our genome, there are millions of sequence codes or structure in small regions that differ between individuals, giving us different characteristics of appearance or responsiveness to medical treatments. Currently, [...] Read more.

Even though each of us shares more than 99% of the DNA sequences in our genome, there are millions of sequence codes or structure in small regions that differ between individuals, giving us different characteristics of appearance or responsiveness to medical treatments. Currently, genetic variants in diseased tissues, such as tumors, are uncovered by exploring the differences between the reference genome and the sequences detected in the diseased tissue. However, the public reference genome was derived with the DNA from multiple individuals. As a result of this, the reference genome is incomplete and may misrepresent the sequence variants of the general population. The more reliable solution is to compare sequences of diseased tissue with its own genome sequence derived from tissue in a normal state. As the price to sequence the human genome has dropped dramatically to around $1000, it shows a promising future of documenting the personal genome for every individual. However, de novo assembly of individual genomes at an affordable cost is still challenging. Thus, till now, only a few human genomes have been fully assembled. In this review, we introduce the history of human genome sequencing and the evolution of sequencing platforms, from Sanger sequencing to emerging “third generation sequencing” technologies. We present the currently available de novo assembly and post-assembly software packages for human genome assembly and their requirements for computational infrastructures. We recommend that a combined hybrid assembly with long and short reads would be a promising way to generate good quality human genome assemblies and specify parameters for the quality assessment of assembly outcomes. We provide a perspective view of the benefit of using personal genomes as references and suggestions for obtaining a quality personal genome. Finally, we discuss the usage of the personal genome in aiding vaccine design and development, monitoring host immune-response, tailoring drug therapy and detecting tumors. We believe the precision medicine would largely benefit from bioinformatics solutions, particularly for personal genome assembly. Full article

(This article belongs to the Special Issue Personalized Medicine and Pharmacogenomics)

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Open AccessArticle

Nanoparticle-Laden Contact Lens for Controlled Ocular Delivery of Prednisolone: Formulation Optimization Using Statistical Experimental Design

by Amr ElShaer, Shelan Mustafa, Mohamad Kasar, Sapana Thapa, Baljit Ghatora and Raid G. Alany

Pharmaceutics 2016, 8(2), 14; https://doi.org/10.3390/pharmaceutics8020014 - 20 Apr 2016

Cited by 66 | Viewed by 9028

Abstract

Human eye is one of the most accessible organs in the body, nonetheless, its physiology and associated precorneal factors such as nasolacrimal drainage, blinking, tear film, tear turnover, and induced lacrimation has significantly decreased the residence time of any foreign substances including pharmaceutical [...] Read more.

Human eye is one of the most accessible organs in the body, nonetheless, its physiology and associated precorneal factors such as nasolacrimal drainage, blinking, tear film, tear turnover, and induced lacrimation has significantly decreased the residence time of any foreign substances including pharmaceutical dosage forms. Soft contact lenses are promising delivery devices that can sustain the drug release and prolong residence time by acting as a geometric barrier to drug diffusion to tear fluid. This study investigates experimental parameters such as composition of polymer mixtures, stabilizer and the amount of active pharmaceutical ingredient on the preparation of a polymeric drug delivery system for the topical ocular administration of Prednisolone. To achieve this goal, prednisolone-loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles were prepared by single emulsion solvent evaporation method. Prednisolone was quantified using a validated high performance liquid chromatography (HPLC) method. Nanoparticle size was mostly affected by the amount of co-polymer (PLGA) used whereas drug load was mostly affected by amount of prednisolone (API) used. Longer homogenization time along with higher amount of API yielded the smallest size nanoparticles. The nanoparticles prepared had an average particle size of 347.1 ± 11.9 nm with a polydispersity index of 0.081. The nanoparticles were then incorporated in the contact lens mixture before preparing them. Clear and transparent contact lenses were successfully prepared. When the nanoparticle (NP)-loaded contact lenses were compared with control contact lenses (unloaded NP contact lenses), a decrease in hydration by 2% (31.2% ± 1.25% hydration for the 0.2 g loaded NP contact lenses) and light transmission by 8% (unloaded NP contact lenses 94.5% NP 0.2 g incorporated contact lenses 86.23%). The wettability of the contact lenses remained within the desired value (<90 °C) even upon incorporation of the NP. NP alone and NP-loaded contact lenses both displayed a slow in vitro drug release of drug over 24 h; where 42.3% and 10.8% prednisolone release were achieved, respectively. Contact lenses can be used as a medicated device to sustain ocular drug delivery and improve patient compliance; nonetheless, patients and healthcare professionals’ acceptability and perceptions of the new formulations entail further investigations. Full article

(This article belongs to the Special Issue Feature Papers: Emerging Processes, Analytics and Dosage Forms in Pharmaceutical Processing and Drug Delivery)

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Open AccessFeature PaperCommunication

Turning Waste into Value: Nanosized Natural Plant Materials of Solanum incanum L. and Pterocarpus erinaceus Poir with Promising Antimicrobial Activities

by Sharoon Griffin, Nassifatou Koko Tittikpina, Adel Al-marby, Reem Alkhayer, Polina Denezhkin, Karolina Witek, Koffi Apeti Gbogbo, Komlan Batawila, Raphaël Emmanuel Duval, Muhammad Jawad Nasim, Nasser A. Awadh-Ali, Gilbert Kirsch, Patrick Chaimbault, Karl-Herbert Schäfer, Cornelia M. Keck, Jadwiga Handzlik and Claus Jacob

Pharmaceutics 2016, 8(2), 11; https://doi.org/10.3390/pharmaceutics8020011 - 19 Apr 2016

Cited by 22 | Viewed by 7106

Abstract

Numerous plants are known to exhibit considerable biological activities in the fields of medicine and agriculture, yet access to their active ingredients is often complicated, cumbersome and expensive. As a consequence, many plants harbouring potential drugs or green phyto-protectants go largely unnoticed, especially [...] Read more.

Numerous plants are known to exhibit considerable biological activities in the fields of medicine and agriculture, yet access to their active ingredients is often complicated, cumbersome and expensive. As a consequence, many plants harbouring potential drugs or green phyto-protectants go largely unnoticed, especially in poorer countries which, at the same time, are in desperate need of antimicrobial agents. As in the case of plants such as the Jericho tomato, Solanum incanum, and the common African tree Pterocarpus erinaceus, nanosizing of original plant materials may provide an interesting alternative to extensive extraction and isolation procedures. Indeed, it is straightforward to obtain considerable amounts of such common, often weed-like plants, and to mill the dried material to more or less uniform particles of microscopic and nanoscopic size. These particles exhibit activity against Steinernema feltiae or Escherichia coli, which is comparable to the ones seen for processed extracts of the same, respective plants. As S. feltiae is used as a model nematode indicative of possible phyto-protective uses in the agricultural arena, these findings also showcase the potential of nanosizing of crude “waste” plant materials for specific practical applications, especially—but not exclusively—in developing countries lacking a more sophisticated industrial infrastructure. Full article

(This article belongs to the Special Issue Nanocrystals)

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Open AccessReview

Timing of Administration: For Commonly-Prescribed Medicines in Australia

by Gagandeep Kaur, Craig L. Phillips, Keith Wong, Andrew J. McLachlan and Bandana Saini

Pharmaceutics 2016, 8(2), 13; https://doi.org/10.3390/pharmaceutics8020013 - 15 Apr 2016

Cited by 19 | Viewed by 9884

Abstract

Chronotherapy involves the administration of medication in coordination with the body’s circadian rhythms to maximise therapeutic effectiveness and minimise/avoid adverse effects. The aim of this study is to investigate the “time of administration” recommendations on chronotherapy for commonly-prescribed medicines in Australia. This study [...] Read more.

Chronotherapy involves the administration of medication in coordination with the body’s circadian rhythms to maximise therapeutic effectiveness and minimise/avoid adverse effects. The aim of this study is to investigate the “time of administration” recommendations on chronotherapy for commonly-prescribed medicines in Australia. This study also aimed to explore the quality of information on the timing of administration presented in drug information sources, such as consumer medicine information (CMI) and approved product information (PI). Databases were searched for original research studies reporting on the impact of “time of administration” of the 30 most commonly-prescribed medicines in Australia for 2014. Further, time of administration recommendations from drug information sources were compared to the evidence from chronotherapy trials. Our search revealed 27 research studies, matching the inclusion and exclusion criteria. In 56% (n = 15) of the research studies, the therapeutic effect of the medicine varied with the time of administration, i.e., supported chronotherapy. For some medicines (e.g., simvastatin), circadian-based optimal administration time was evident in the information sources. Overall, dedicated studies on the timing of administration of medicines are sparse, and more studies are required. As it stands, information provision to consumers and health professionals about the optimal “time” to take medications lags behind emerging evidence. Full article

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Open AccessArticle

Evaluation of P-Glycoprotein Inhibitory Potential Using a Rhodamine 123 Accumulation Assay

by Elodie Jouan, Marc Le Vée, Abdullah Mayati, Claire Denizot, Yannick Parmentier and Olivier Fardel

Pharmaceutics 2016, 8(2), 12; https://doi.org/10.3390/pharmaceutics8020012 - 12 Apr 2016

Cited by 116 | Viewed by 11074

Abstract

In vitro evaluation of P-glycoprotein (P-gp) inhibitory potential is now a regulatory issue during drug development, in order to predict clinical inhibition of P-gp and subsequent drug–drug interactions. Assays for this purpose, commonly based on P-gp-expressing cell lines and digoxin as a reference [...] Read more.

In vitro evaluation of P-glycoprotein (P-gp) inhibitory potential is now a regulatory issue during drug development, in order to predict clinical inhibition of P-gp and subsequent drug–drug interactions. Assays for this purpose, commonly based on P-gp-expressing cell lines and digoxin as a reference P-gp substrate probe, unfortunately exhibit high variability, raising thus the question of developing alternative or complementary tests for measuring inhibition of P-gp activity. In this context, the present study was designed to investigate the use of the fluorescent dye rhodamine 123 as a reference P-gp substrate probe for characterizing P-gp inhibitory potential of 16 structurally-unrelated drugs known to interact with P-gp. 14/16 of these P-gp inhibitors were found to increase rhodamine 123 accumulation in P-gp-overexpressing MCF7R cells, thus allowing the determination of their P-gp inhibitory potential, i.e., their half maximal inhibitor concentration (IC₅₀) value towards P-gp-mediated transport of the dye. These IC₅₀ values were in the range of variability of previously reported IC₅₀ for P-gp and can be used for the prediction of clinical P-gp inhibition according to Food and Drug Administration (FDA) criteria, with notable sensitivity (80%). Therefore, the data demonstrated the feasibility of the use of rhodamine 123 for evaluating the P-gp inhibitory potential of drugs. Full article

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Open AccessReview

Small Angle X-ray and Neutron Scattering: Powerful Tools for Studying the Structure of Drug-Loaded Liposomes

by Emanuela Di Cola, Isabelle Grillo and Sandra Ristori

Pharmaceutics 2016, 8(2), 10; https://doi.org/10.3390/pharmaceutics8020010 - 28 Mar 2016

Cited by 79 | Viewed by 11080

Abstract

Nanovectors, such as liposomes, micelles and lipid nanoparticles, are recognized as efficient platforms for delivering therapeutic agents, especially those with low solubility in water. Besides being safe and non-toxic, drug carriers with improved performance should meet the requirements of (i) appropriate size and [...] Read more.

Nanovectors, such as liposomes, micelles and lipid nanoparticles, are recognized as efficient platforms for delivering therapeutic agents, especially those with low solubility in water. Besides being safe and non-toxic, drug carriers with improved performance should meet the requirements of (i) appropriate size and shape and (ii) cargo upload/release with unmodified properties. Structural issues are of primary importance to control the mechanism of action of loaded vectors. Overall properties, such as mean diameter and surface charge, can be obtained using bench instruments (Dynamic Light Scattering and Zeta potential). However, techniques with higher space and time resolution are needed for in-depth structural characterization. Small-angle X-ray (SAXS) and neutron (SANS) scattering techniques provide information at the nanoscale and have therefore been largely used to investigate nanovectors loaded with drugs or other biologically relevant molecules. Here we revise recent applications of these complementary scattering techniques in the field of drug delivery in pharmaceutics and medicine with a focus to liposomal carriers. In particular, we highlight those aspects that can be more commonly accessed by the interested users. Full article

(This article belongs to the Special Issue Liposome Technologies 2015)

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Pharmaceutics, Volume 8, Issue 2 (June 2016) – 10 articles

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