Current Pharmaceutical Biotechnology - Volume 16, Issue 4, 2015

Biopharmaceuticals comprise therapeutic protein-based, nucleic acids and cell-based products. According to their therapeutic success, the clinical use of these products has been growing. Therefore, the development of efficient biopharmaceuticals delivery systems, which overcome their limitations for administration, remains an excellent prospect for pharmaceutical technologists. In this area, lipid nanoparticles have been increasingly recognized as one of the most promising delivery systems, due to their exclusive advantages. However, no clinical biopharmaceutical lipid nanoparticle-based products are yet available. This fact could be explained by the lack or failure of in vivo studies, regarding stability and toxicological concerns, and also by the complex regulatory issues that must be accomplished. The present review article focuses on the different classes of biopharmaceuticals, their characteristics and limitations for administration. A state of the art regarding the use of lipid nanoparticles to improve biopharmaceuticals delivery is presented and a critical prospect of the future directions that should be addressed by pharmaceutical technologists is also discussed.

Proliposomes are phospholipid based drug delivery systems that are finding important applications in the field of pharmaceutics. Proliposomes have been extensively studied as a potential carrier for oral delivery of drugs with poor bioavailability, but the mechanism of absorption and cellular uptake pathways has not yet been clearly understood. An in-depth insight into the physical and biological behavior of proliposomes is necessary for designing an effective delivery system for enhancing the availability of drug at the intended site. Reformulation of sub optimal drugs using proliposomes has given an opportunity to improve the therapeutic indices of various drugs predominantly by altering their uptake mechanism. This work reviews the proliposomal drug delivery field, summarizes the success of proliposomes for the oral delivery of drugs with poor bioavailability; indicating the key issues to be addressed to affirm that proliposomes can effectively work as a drug carrier in clinical settings with a clear understanding of its behavior in biological environment, as they are now an established platform technology with considerable clinical acceptance.

Cubosomes are formed by amphiphilic molecules, with the bicontinuous contortions of inter-connecting hydrophilic and hydrophobic domains. The inner cubic-phase structure of cubosomes makes it an attractive drug-delivery system in pharmaceutical applications. This review mainly describes the potential applications of cubosomes as a drug delivery system for oral administration, highlights the mechanisms involved in the transcellular transport and digestive process, challenges involved in formulation development and evaluations of the in vivo and in vitro study. As pointed out throughout this review, a number of critical points on cubosome products need to be solved in order to attain practical applications.

Lipid nanocapsules with their unique composition represent a promising biocompatible drug delivery platform in nanometer range with narrow size distribution. They are highly stable in comparison to other nano-vectors and were found to impart very desirable characteristics to the therapeutic molecule being delivered within. The current review sheds the light on the methods of preparation of lipid nanocapsules, which are simple and easily scalable, in addition to providing examples of post insertion of some compounds for prolonging vascular circulation, protection, and targeting several diseases. In addition, the review discusses the vast in vitro and in vivo applications of lipid nanocapsules when administered via different routes such as oral, parenteral and transdermal routes. Promising use of nanocapsules in treatment of cancer, Alzheimer’s disease, dermatological conditions and other miscellaneous applications are highlighted.

Among all available lipid based nanoparticulate systems, the success of liposomal drug delivery system is evident by the number of liposomal products available in the market or under advanced stages of preclinical and clinical trials. Liposome has the ability to deliver chemotherapeutic agents to the targeted tissues or even inside the cancerous cells by enhanced intracellular penetration or improved tumour targeting. In the last decade, folate receptor mediated tumour targeting has emerged as an attractive alternative method of active targeting of cancer cells through liposomes due to its numerous advantages over other targeting methods. Folate receptors, also known as folate binding proteins, allow the binding and internalization of folate or folic acid into the cells by a method called folate receptor mediated endocytosis. They have restricted presence in normal cells and are mostly expressed during malignant transformation. In this review article, folate receptor targeting capability of liposomes has been described. This review article has focussed on the different cancer drugs which have been encapsulated in folate receptor targeted liposomes and their in vitro as well as in vivo efficacies in several tumour models.

Vesicular systems exhibit many attractive properties such as controlled drug release, ability to carry both hydrophilic and hydrophobic drugs, targetability and good biocompatibility. With these unique properties they can provide improved drug bioavailability and reduced side effects. Until now, many vesicular formulations have been studied in clinical and preclinical stages. Nevertheless, the major concern about these systems is their low physicochemical stability and high manufacturing expenses. The stability problems (fusion, aggregation, sedimentation, swelling, and drug leakage during storage) associated with the aqueous nature of vesicular systems hinders their effective usage. The advances on improving the stability of vesicular systems led to the emergence of provesicular systems, which are commonly described as dry, free flowing preformulations of vesicular drug delivery systems. Provesicles form vesicular systems upon hydratation with water and exhibit the advantages of vesicular systems with improved stability. The present article briefly reviews vesicular systems (particularly liposomes and niosomes) and enlightens about the innovations in the field. Overall investigations are reviewed and the provesicle approach is explained by giving detailed information on the composition, preparation, administration and characterization methods of provesicular systems (proliposomes and proniosomes). The scope of this article is expected to give insight to the researchers and industrialists to perform further research in this area.

Essential oils have increased interest as promising ingredients for novel pharmaceutical dosage forms. These oils are reported to provide synergistic effects of their active ingredients, in parallel with their biodegradable properties. In addition, essential oils may also have therapeutic effects in diabetes, inflammation, cancer and to treat microbial infections. However, there are some physicochemical properties that may limit their use as active compounds in several formulations, such as high volatility, low-appealing organoleptic properties, low bioavailability and physicochemical instability, as result of exposure to light, oxygen and high temperatures. To overcome these limitations, lipid colloidal carriers (e.g. liposomes, solid lipid nanoparticles (SLN), self nanoemulsified drug delivery systems (SNEDDS)) have been pointed out as suitable carriers to improve bioavailability, low solubility, taste, flavor and long-term storage of sensitive compounds. This paper reviews the potential beneficial effects of formulating essential oils in pharmaceutical applications using colloidal carriers as delivery systems. Keywords: essential oils, colloidal system, encapsulation, biological effect, chemotherapy.

Transcutaneous vaccination has become a widely used technique for providing immunity against several types of pathogens, taking advantage of the immune components found in the skin. The success in the field of vaccination has not only relied on the type of antigen and adjuvant delivered, but also on how they are delivered. In this regard, particulate carriers, especially nanoparticles have evoked considerable interest, owing to the desirable properties that they impart to the substance being delivered. The presentation of antigens by the nanoparticles mimics the presentation of the immunogen by the pathogen; hence, it creates a similar immune response. Furthermore, nanoparticles protect the antigen from degradation and allow its prolonged release, which maximizes its exposure to the immune cells. The most commonly used materials for the formulation of nanoparticles are either polymer-based or lipid based. This review will focus on the lipid based nanocarriers, either vesicular such as liposomes, transfersomes, and ethosomes, or non-vesicular such as cubosomes, solid lipid nanoparticles, nano-structured lipid carriers, solid in oil nanodispersions, lipoplexes, and hybrid polymeric-lipidic systems. The applications of these carriers in the field of transcutaneous immunization will be discussed in this review as well.

Lipid based vesicular drug delivery system, one of the emerging technologies designed for addressing the delivery challenges of conventional drug delivery methods, has widespread applications in chemotherapeutics, immunotherapeutics, recombinant DNA technology, membrane biology and also as a diagnostic tool in different biological field. The enclosed phospholipid bilayer spherical structure, typically known as liposome, is a versatile vesicular delivery system to carry hydrophilic/hydrophobic drug generally efficiently to the site of action leading to reduced non-specific toxicity and improved bioavailability of the therapeutic moiety. Efficacy of drug encapsulated in liposome depends mainly on the circulation amount of liposome and its residence time, in vivo drug release, drug accumulation in the target site and uptake of the formulation in the reticuloendothelial system. Liposomal formulation factors that dictate those actions are liposomal size (hydrodynamic diameter), surface charge, lipid composition and steric stabilization. Variation in liposomal size shows around 100 fold alterations in pharmacokinetic parameters and systemic activity while the other factors such as surface charge, lipid composition and steric stabilization bring only about 10 fold changes in those properties. The findings indicate the critical role of vesicular size in liposomal efficacy. In the present review the effect of size-variation of liposome on systemic activity of drug as well as its pharmacokinetic profile will be discussed to understand the rational designing of liposomal preparation to maximize therapeutic activity of a drug at desired magnitude and to provide a wide range of product applications such as immunological vaccines, chemotherapy, antimicrobial therapy etc.

Here, the use of emulsomes as a drug delivery system is reviewed and compared with other similar lipidic nanoformulations. In particular, we look at surface modification of emulsomes using S-layer proteins, which are self-assembling proteins that cover the surface of many prokaryotic organisms. It has been shown that covering emulsomes with a crystalline S-layer lattice can protect cells from oxidative stress and membrane damage. In the future, the capability to recrystallize S-layer fusion proteins on lipidic nanoformulations may allow the presentation of binding functions or homing protein domains to achieve highly specific targeted delivery of drug-loaded emulsomes. Besides the discussion on several designs and advantages of composite emulsomes, the success of emulsomes for the delivery of drugs to fight against viral and fungal infections, dermal therapy, cancer, and autoimmunity is summarized. Further research might lead to smart, biocompatible emulsomes, which are able to protect and reduce the side effects caused by the drug, but at the same time are equipped with specific targeting molecules to find the desired site of action.