Lipid-based Drug Carriers Research Articles

Cholinized-Polymer Functionalized Lipid-Based Drug Carriers Facilitate Liver Fibrosis Therapy via Ultrafast Liver-Targeting Delivery.

Here, we report novel cholinized-polymer functionalized lipid-based nanoparticles (CP-LNPs) for rapid and highly effective delivery of drugs to the liver, achieving targeting within 10 min and nearly 100% efficiency. In this study, CP-LNPs loaded with a promising antifibrotic agent curcumin (CP-LNPs/Cur) significantly improved the stability of curcumin under physiological conditions and its distribution in the liver. In vitro experiments demonstrated that CP-LNPs/Cur effectively suppressed the proliferation and migration of activated hepatic stellate cells (aHSCs), as evidenced by the decreased expression of α-SMA. Moreover, CP-LNPs/Cur attenuated oxidative stress levels in hepatocytes while improving mitochondrial physiological activity. In vivo antifibrosis studies have shown that CP-LNPs/Cur only require a low dose to significantly alleviate liver injury and collagen deposition, thereby preventing the progression of liver fibrosis. These findings indicated that CP-LNPs exhibit great potential in liver fibrosis therapy benefiting from the novel targeting strategy.

Tailor-made vincristine-liposomes for tumor targeting

To ensure selective targeting based on membrane fluidity and physico-chemical compatibility between the biological membrane of the target cell and the lipid membrane of the liposomes carriers. Lipid-based carriers as liposomes with varying membrane fluidities were designed for delivering vincristine, an anti-tumor compound derived from Madagascar's periwinkle. Liposomes, loaded with vincristine, were tested on prostate, colon, and breast cancer cell lines alongside non-tumor controls. Results showed that vincristine-loaded liposomes with fluid membranes significantly decreased the viability of cancer cell lines compared to controls. Confocal microscopy revealed the intracellular release of vincristine, evidenced by disrupted mitosis-specific labeling of actin filaments in metastatic prostate cell lines. This highlights the crucial role of membrane fluidity in the development of lipid-based drug carriers, offering a promising and cost-effective option for targeting cancer cells as an alternative to conventional strategies.

Digestion of lipid micelles leads to increased membrane permeability.

Lipid-based drug carriers are an attractive option to solubilise poorly water soluble therapeutics. Previously, we reported that the digestion of a short tail PC lipid (2C6PC) by the PLA2 enzyme has a significant effect on the structure and stability of the micelles it forms. Here, we studied the interactions of micelles of varying composition representing various degrees of digestion with a model ordered (70 mol% DPPC & 30 mol% cholesterol) and disordered (100% DOPC) lipid membrane. Micelles of all compositions disassociated when interacting with the two different membranes. As the percentage of digestion products (C6FA and C6LYSO) in the micelle increased, the disassociation occurred more rapidly. The C6FA inserts preferentially into both membranes. We find that all micelle components increase the area per lipid, increase the disorder and decrease the thickness of the membranes, and the 2C6PC lipid molecules have the most significant impact. Additionally, there is an increase in permeation of water into the membrane that accompanies the insertion of C6FA into the DOPC membranes. We show that the natural digestion of lipid micelles result in molecular species that can enhance the permeability of lipid membranes that in turn result in an enhanced delivery of drugs.

Advances in lipid-based carriers for cancer therapeutics: Liposomes, exosomes and hybrid exosomes

Cancer has recently surpassed heart disease as the leading cause of deaths worldwide for the age group 45–65 and has been the primary focus for biomedical researchers. Presently, the drugs involved in the first-line cancer therapy are raising concerns due to high toxicity and lack of selectivity to cancer cells. There has been a significant increase in research with innovative nano formulations to entrap the therapeutic payload to enhance efficacy and eliminate or minimize toxic effects. Lipid-based carriers stand out due to their unique structural properties and biocompatible nature. The two main leaders of lipid-based drug carriers: long known liposomes and comparatively new exosomes have been well-researched. The similarity between the two lipid-based carriers is the vesicular structure with the core's capability to carry the payload. While liposomes utilize chemically derived and altered phospholipid components, the exosomes are naturally occurring vesicles with inherent lipids, proteins, and nucleic acids. More recently, researchers have focused on developing hybrid exosomes by fusing liposomes and exosomes. Combining these two types of vesicles may offer some advantages such as high drug loading, targeted cellular uptake, biocompatibility, controlled release, stability in harsh conditions and low immunogenicity.

Intranasal Polymeric and Lipid-Based Nanocarriers for CNS Drug Delivery

Nanomedicine is currently focused on the design and development of nanocarriers that enhance drug delivery to the brain to address unmet clinical needs for treating neuropsychiatric disorders and neurological diseases. Polymer and lipid-based drug carriers are advantageous for delivery to the central nervous system (CNS) due to their safety profiles, drug-loading capacity, and controlled-release properties. Polymer and lipid-based nanoparticles (NPs) are reported to penetrate the blood-brain barrier (BBB) and have been extensively assessed in in vitro and animal models of glioblastoma, epilepsy, and neurodegenerative disease. Since approval by the Food and Drug Administration (FDA) of intranasal esketamine for treatment of major depressive disorder, intranasal administration has emerged as an attractive route to bypass the BBB for drug delivery to the CNS. NPs can be specifically designed for intranasal administration by tailoring their size and coating with mucoadhesive agents or other moieties that promote transport across the nasal mucosa. In this review, unique characteristics of polymeric and lipid-based nanocarriers desirable for drug delivery to the brain are explored in addition to their potential for drug repurposing for the treatment of CNS disorders. Progress in intranasal drug delivery using polymeric and lipid-based nanostructures for the development of treatments of various neurological diseases are also described.

Encapsulation and release of hydrocortisone from proliposomes govern vaginal delivery.

Topical preparations of hydrocortisone can be used for the anti-inflammatory treatment of the female genital area. Although the drug is a low-strength corticosteroid, systemic absorption and distribution of the drug are the most common safety risks associated with this therapy. In the current investigation, we elucidate the physicochemical properties of lipid-based drug carrier systems that govern the local bioavailability of hydrocortisone for intravaginal administration. For this purpose, we compared various proliposome formulations with a commercial cream. Depending on the availability of physiological acceptors, encapsulation and drug release from the lipid phase were found to be the most important drivers of drug bioavailability. The high permeability of hydrocortisone leads to rapid transport of the drug across the mucosal cell layer as indicated by experiments using HEC-1-A and CaSki cell monolayer models. Under sink conditions, differences in the release from the liposomes as determined in the Dispersion Releaser were almost negligible. However, under non-sink conditions, the drug release plateaued at levels corresponding to the encapsulation efficiency. After redispersion, all liposomal formulations performed better than the commercial drug product indicating that the encapsulation into the lipid phase is the main driver sustaining the release.

Single-vesicle intensity and colocalization fluorescence microscopy to study lipid vesicle fusion, fission, and lipid exchange.

Interactions of lipid vesicles play important roles in a large variety of functions and dysfunctions in the human body. Vital for several biochemical functions is the interaction between monomeric proteins and lipid membranes, and the induced phenomena such as fusion between vesicles and cell membranes, lipid exchange between the membranes, or vesicle fission. Identification of single events and their frequency of occurrence would provide valuable information about protein-lipid interactions in both healthy and degenerative pathways. In this work, we present a single-vesicle intensity and colocalization fluorescence microscopy assay with a custom-written MATLAB analysis program. The assay can be used to study lipid exchange as well as vesicle fusion and fission between two vesicle populations labeled with different fluorescent dyes. Vesicles from the two populations are first mixed and docked to a glass surface. The sample is then simultaneously imaged using two separate wavelength channels monitoring intensity changes and colocalization of vesicles from the two populations. The monomeric pre-synaptic protein α-synuclein (α-syn) and small unilamellar vesicles consisting of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), 1,2-dioleoyl-sn-glycero-3-phospho-L-serine, (DOPS), and monosialotetrahexosylganglioside (GM1) were used as a model system to evaluate the method. From our analysis, neither α-syn induced fusion nor lipid exchange was observed for vesicles consisting of DOPC:DOPS (7:3). However, including 10% GM1 in the vesicles resulted in a 91% increase of the number of vesicles within 10 min, combined with a 57% decrease in the average fluorescence intensity per vesicle, indicating that approximately half of the vesicles underwent fission. The method facilitates the study of lipid vesicle fusion, fission, and lipid exchange under controlled conditions. It also allows these events to be studied for systems with more complex composition including exosomes and lipid-based drug carriers, to enable a better understanding of their physicochemical properties.

Liposomes trigger bone marrow niche macrophage “foam” cell formation and affect hematopoiesis in mice

Liposomes are the most widely used nanocarrier platform for the delivery of therapeutic and diagnostic agents, and a number of liposomes have been approved for use in clinical practice. After systemic administration, most liposomes are cleared by macrophages in the mononuclear phagocyte system, such as the liver and bone marrow (BM). However, the majority of studies have focused on investigating the therapeutic results of liposomal drugs, and too few studies have evaluated the potential side effects of empty nanocarriers on the functions of macrophages in the mononuclear phagocyte system. Here, we evaluate the potential effects of empty liposomes on the functions of BM niche macrophages. Following liposome administration, we observed lipid droplet (LD) accumulation in cultured primary macrophages and BM niche macrophages. We found that these LD-accumulating macrophages, similar to foam cells, exhibited increased expression of inflammatory cytokines, such as IL-1β and IL-6. We further provided evidence that liposome deposition and degradation induced LD biogenesis on the endoplasmic reticulum membrane and subsequently disturbed endoplasmic reticulum homeostasis and activated the inositol-requiring transmembrane kinase/endoribonuclease 1α/NF-κB signaling pathway, which is responsible for the inflammatory activation of macrophages after liposome engulfment. Finally, we also showed the side effects of dysfunctional BM niche macrophages on hematopoiesis in mice, such as the promotion of myeloid-biased output and impairment of erythropoiesis. This study not only draws attention to the safety of liposomal drugs in clinical practice but also provides new directions for the design of lipid-based drug carriers in preclinical studies.

Primaquine Loaded Solid Lipid Nanoparticles (SLN), Nanostructured Lipid Carriers (NLC), and Nanoemulsion (NE): Effect of Lipid Matrix and Surfactant on Drug Entrapment, in vitro Release, and ex vivo Hemolysis.

Primaquine (PQ), an 8-aminoquinoline antimalarial drug, has been widely used for the eradication of hypnozoites from the liver and, therefore, recognized as the radical cure of malaria. However, the clinical applications of PQ are restricted to patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency due to severe dose-related hemolytic side effects. Nanoparticle carriers have shown great potential in achieving higher PQ concentrations in the target site, thereby reducing dose-related systemic toxicity caused by non-specific exposure. This work aims to develop, compare, and evaluate three PQ-loaded lipid-based drug carriers including solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC), and nano-emulsions (NE). The optimized PQ-SLN, PQ-NLC, and PQ-NE had a particle size of 250nm, a PDI range of 0.1 to 0.3, a zeta potential of - 30mV, and entrapment efficiency of ~ 90%. All lipid formulations showed sustained release in both simulated gastric and intestinal fluids over 6h. Four empirical models - including zero-order, Higuchi, Korsmeyer-Peppas, and Hixson-Crowell models - were tested to understand the drug release mechanisms of PQ-SLN, PQ-NLC, and PQ-NE. The model fitness was found to be the highest in the Korsmeyer-Peppas model for all the PQ-loaded lipid formulations (R2: 0.88-0.94). No significant changes were observed in the entrapment efficiency, particle size, and PDI of lipid formulations throughout 1month of storage at 4°C and 25°C. PQ-SLN and PQ-NLC can be further lyophilized with cryoprotectants to improve long-term stability. Finally, the treatment of erythrocytes with PQ-SLN, PQ-NLC, and PQ-NE reduced erythrocyte hemolysis by approximately 4.5-fold compared to the free drug solution.

Liposome Characterization, Applications and Regulatory landscape in US

Liposomes are lipid based drug carrier whose therapeutic performance depends on their structure. Liposomes offer several advantages over the conventional drug like target drug delivery, reduced toxicity, and extended pharmacokinetics. Characterization and Identification of critical attribute of liposomal formulation and suitable strategies for control during product development is important for quality of the liposomal drug product. This paper discusses the current status of the liposomal drug product and strategy used in regulating liposome product. Despite of lack of regulatory guidelines many liposome formulations get approved which shows the potential of liposome drug products.

Exploring potential formulation strategies for chemoprevention of breast cancer: a localized delivery perspective.

This review focuses on the various formulation approaches that have been explored to achieve localized delivery in breast cancer. The rationale behind the necessity of localized drug delivery has been extensively reviewed. The review also emphasizes the various possible routes for achieving localized drug delivery. Particularly, different types of nanoplatforms like lipid-based drug carriers, polymeric particles, hydrogels, drug conjugates and other formulation strategies like microneedles and drug-eluting implants, which have been used to increase tumor retention and subsequently halt tumor progression, have been deliberated here. In addition, the significant challenges that may be encountered in the delivery of anticancer drugs and the aspects that require careful evaluation for effective localized delivery of chemotherapeutic agents have been discussed.

Formulating and Characterizing Lipid Nanoparticles for Gene Delivery using a Microfluidic Mixing Platform.

Lipid-based drug carriers have been used for clinically and commercially available delivery systems due to their small size, biocompatibility, and high encapsulation efficiency. Use of lipid nanoparticles (LNPs) to encapsulate nucleic acids is advantageous to protect the RNA or DNA from degradation, while also promoting cellular uptake. LNPs often contain multiple lipid components including an ionizable lipid, helper lipid, cholesterol, and polyethylene glycol (PEG) conjugated lipid. LNPs can readily encapsulate nucleic acids due to the ionizable lipid presence, which at low pH is cationic and allows for complexation with negatively charged RNA or DNA. Here LNPs are formed by encapsulating messenger RNA (mRNA) or plasmid DNA (pDNA) using rapid mixing of the lipid components in an organic phase and the nucleic acid component in an aqueous phase. This mixing is performed using a precise microfluidic mixing platform, allowing for nanoparticle self-assembly while maintaining laminar flow. The hydrodynamic size and polydispersity are measured using dynamic light scattering (DLS). The effective surface charge on the LNP is determined by measuring the zeta potential. The encapsulation efficiency is characterized using a fluorescent dye to quantify entrapped nucleic acid. Representative results demonstrate the reproducibility of this method and the influence that different formulation and process parameters have on the developed LNPs.

Role of stealth lipids in nanomedicine-based drug carriers

The domain of nanomedicine owns a wide-ranging variety of lipid-based drug carriers, and novel nanostructured drug carriersthat are further added to this range every year. The primary goal behind the exploration of any new lipid-based nanoformulation is the improvement of the therapeutic index of the concerned drug molecule along with minimization in the associated side-effects. However, for maintaining a sustained delivery of these intravenously injected lipoidal nanomedicines to the targeted tissues and organ systems in the body, longer circulation in the bloodstream, as well as their stability, are important. After administration, upon recognition as foreign entities in the body, these systems are rapidly cleared by the cells associated with the mononuclear phagocyte system. In order to provide these lipid-based systems with long circulation characteristics, techniques such as coating of the lipoidal surface with an inert polymeric material like polyethylene glycol (PEG) assists in imparting ‘stealth properties’ to these nanoformulations for avoiding recognition by the macrophages of the immune system. In this review, detailed importance is given to the hydrophilic PEG polymer and the role played by PEG-linked lipid polymers in the field of nanomedicine-based drug carriers. The typical structure and classification of stealth lipids, clinical utility, assemblage techniques, physicochemical characterization, and factors governing the in-vivo performance of the PEG-linked lipids containing formulations will be discussed. Eventually, the novel concept of accelerated blood clearance (ABC) phenomenon associated with the use of PEGylated therapeutics will be deliberated.

Polymer-Lipid Hybrid Systems: Scope of Intravenous-To-Oral Switch in Cancer Chemotherapy

Cancer chemotherapeutic administration by oral route has the potential to create “hospitalization free chemotherapy”. Such a therapeutic approach will improve patient compliance and significantly reduce the cost of treatment. In current clinical practice, chemotherapy is primarily carried out by intravenous injection or infusion and leads to various unwanted effects. Despite the presence of oral delivery challenges like poor aqueous solubility, low permeability, drug stability and substrate for multidrug efflux transporter, cancer chemotherapy delivery through oral administration has gained much attention recently due to having more patient compliance compared to the intravenous mode of administration. In order to address the multifaceted oral drug delivery challenges, a hybrid delivery system is conceptualized to merge the benefits of both polymeric and lipid-based drug carriers. Polymer-lipid hybrid systems have presented various significant benefits as an efficient carrier to facilitate oral drug delivery by surmounting the different associated obstacles. This carrier system has been found suitable to overcome the numerous oral absorption hindrances and facilitate the intravenous-to-oral switch in cancer chemotherapy. In this review, we aimed to discuss the different biopharmaceutic challenges in oral delivery of cancer chemotherapy and how this hybrid system may provide solutions to such challenges.

Preparation of L-Glutamine Loaded Liposomes for Drug Delivery to Erythrocytes

Sickle cell disease (SCD) is a mortal chronic disease caused by a point mutation in the ? chain gene in the hemoglobin A (HbA) molecule. Erythrocyte polymerization in SCD is mostly seen as a result of the decrease in the amount of ions and water in the cell, i.e. dehydration and deoxygenation of erythrocytes. Deoxygenated and dehydrated erythrocytes become susceptible to clustering, causing clogging of blood vessels which then leads to crisis. Therefore, development of a new treatment method that can effectively prevent deoxygenation of erythrocytes or reduce the oxidative stress of sickle erythrocytes is one of the important issues. The aim of this study is to obtain a new lipid-based drug delivery system that will further be used for decreasing the oxidative stress of sickle erythrocytes. For the purpose, in this study, L-Glutamine (L-Gln) loaded liposomal drug delivery system composed of L-?-Phosphatidylinositol (PI) is prepared. Also, effect of encapsulated amount of L-Gln in liposomes is investigated. Liposomes are prepared via thin-film rehydration method. Characterizations of liposomes are implemented with pH measurements, zeta potential and size measurements. Erythrocytes and liposomes are incubated at 37ºC for 1 and 3 hours. Interactions between the erythrocytes and liposomes are investigated via optical microscopy and hemolysis experiments. The size and zeta potential of unloaded PI liposomes are determined as 89.01 nm with a polydispersity index of 0.438 and -23.4 ± 1.5 mV, respectively. Sizes of L-Gln loaded liposomes are obtained as 126.7, 148.6 and 197.2 nm for 20 mM, 40 mM and 60 mM of L-Gln, respectively. From the optical microscopy images, it is determined that as incubation period of erythrocytes and liposomes are increased, more liposomes are interacted with erythrocytes. Also, as L-Gln amount is increased within the liposomes, it was observed that erythrocytes preserve their morphology. Overall, with this study, it can be concluded that L-Glutamine loaded liposomes can be used as a new drug delivery platform for erythrocytes. Moreover, the results of this study provide preliminary steps and promising results for design and development of a lipid-based drug carrier system to be used in the treatment of specific erythrocyte-based diseases such as sickle-cell disease.

The trip of a drug inside the body: From a lipid-based nanocarrier to a target cell

To date, enormous investigations have been conducted to enhance medicines' target-oriented delivery to improve their therapeutic index. In this regard, lipid-based carrier system might have been regarded as prime delivery systems that are very close to the naturally cell-derived vesicles used for biomolecular communication among cells from occasionally remote tissues. Upon examination of the literature, we found a chasm between groups of investigations in drug pharmaceutics and thought that maybe holistic research could provide better information with respect to drug delivery inside the body, especially when they are going to be injected directly into the bloodstream for systemic distribution. While a collection of older research in most cases dealt with the determination of drug partition coefficient between the aqueous and cell membrane compartments, the link has been overlooked in newer investigations that were mostly focused on drug formulation optimization and their association with particle biodistribution. This gap in the literature motivated us to present the current opinion paper, in which drug physicochemical properties like drug lipophilicity/hydrophilicity is considered as an important element in designing drug-carrying liposomes or micelles. How a hypothetical high throughput cell-embedded chromatographic technique might help to investigate a nanocarrier tissue distribution and to design ‘multi-epitope grafted lipid-based drug carrier systems’ are discussed. Whenever we would need support for our opinions, we have provided analogy from hydrophobic biomolecules like cholesterol, steroid hormones, and sex hormones and encouraged readers to consider our principle hypothesis: If these molecules could reach their targets far away from the site of production, then a large list of hydrophobic drugs could be delivered to their targets using the same principles.

Cisplatin Encapsulation Generates Morphologically Different Multicompartments in the Internal Nanostructures of Nonlamellar Liquid-Crystalline Self-Assemblies.

Cisplatin ( cis-diamminedichloroplatinum(II)) is among the most potent cytotoxic agents used in cancer chemotherapy. The encapsulation of cisplatin in lipid-based drug carriers has been challenging owing to its low solubility in both aqueous and lipid phases. Here, we investigated cisplatin encapsulation in nonlamellar liquid-crystalline (LC) nanodispersions formed from a ternary mixture of phytantriol (PHYT), vitamin E (Vit E), and an anionic phospholipid [either phosphatidylglycerol (DSPG) or phosphatidylserine (DPPS)]. We show an increase in cisplatin encapsulation efficiency (EE) in nanodispersions containing 1.5-4 wt % phospholipid. The EE was highest in DPPS-containing nanodispersions (53-98%) compared to DSPG-containing counterparts (25-40%) under similar experimental conditions. Through structural and morphological characterizations involving synchrotron small-angle X-ray scattering and cryogenic transmission electron microscopy, we further show that varying the phospholipid content of cisplatin-free nanodispersions triggers an internal phase transition from a neat hexagonal (H2) phase to a biphasic phase (internal H2 phase coexisting with the lamellar (Lα) phase). However, cisplatin encapsulation in both DPPS- and DSPG-containing nanodispersions generates the coexistence of morphologically different multicompartments in the internal nanostructures comprising vesicles as a core, enveloped by an inverted-type surface bicontinuous cubic Im3 m (primitive, QIIP) phase or H2 phase. We discuss the biophysical basis of these drug-induced morphological alterations and provide insights into the potential development of inverted-type LC nanodispersions for cisplatin delivery.

Nanodisc-Targeted STD NMR Spectroscopy Reveals Atomic Details of Ligand Binding to Lipid Environments.

Saturation transfer difference (STD) NMR spectroscopy is one of the most popular ligand-based NMR techniques for the study of protein-ligand interactions. This is due to its robustness and the fact that it is focused on the signals of the ligand, without any need for NMR information on the macromolecular target. This technique is most commonly applied to systems involving different types of ligands (e.g., small organic molecules, carbohydrates or lipids) and a protein as the target, in which the latter is selectively saturated. However, only a few examples have been reported where membrane mimetics are the macromolecular binding partners. Here, we have employed STD NMR spectroscopy to investigate the interactions of the neurotransmitter dopamine with mimetics of lipid bilayers, such as nanodiscs, by saturation of the latter. In particular, the interactions between dopamine and model lipid nanodiscs formed either from charged or zwitterionic lipids have been resolved at the atomic level. The results, in agreement with previous isothermal titration calorimetry studies, show that dopamine preferentially binds to negatively charged model membranes, but also provide detailed atomic insights into the mode of interaction of dopamine with membrane mimetics. Our findings provide relevant structural information for the design of lipid-based drug carriers of dopamine and its structural analogues and are of general applicability to other systems.

Innovative lipid-based carriers containing cationic derivatives of polyisoprenoid alcohols augment the antihypertensive effectiveness of candesartan in spontaneously hypertensive rats

Novel lipid-based carriers, composed of cationic derivatives of polyisoprenoid alcohols (amino-prenols, APrens) and 1,2-dioleoyl-sn-glycero-3-phosphatidylethanolamine (DOPE), were designed. The carriers, which were previously shown to be nontoxic to living organisms, were now tested if suitable for administration of candesartan, an antihypertensive drug. Spontaneously hypertensive rats (SHR) received injections of candesartan (0.1 mg/kg body weight per day; s.c.) in freshly prepared carriers for two weeks. The rats' arterial pressure was measured by telemetry. Urine and blood collection were performed in metabolic cages. In a separate group of SHR, the pharmacokinetics of the new formulation was evaluated after a single subcutaneous injection. The antihypertensive activity of candesartan administered in DOPE dispersions containing APrens was distinctly greater than that of candesartan dispersions composed of DOPE only or administered in the classic solvent (sodium carbonate). The pharmacokinetic parameters clearly demonstrated that candesartan in APren carriers reached the bloodstream more rapidly and in much greater concentration (almost throughout the whole observation) than the same drug administered in dispersions of DOPE only or in solvent. Serum creatinine (PCr) decreased significantly only in the group receiving candesartan in carriers with APrens (from 0.80 ± 0.04 to 0.66 ± 0.09 mg/dl; p < 0.05), whereas in the other groups PCr remained at the same level after treatment. Moreover, the new derivatives increased the loading capacity of the carriers, which is a valuable feature for any drug delivery system. Taken together, our findings led us to conclude that APrens are potentially valuable components of lipid-based drug carriers.

Perspectives of Lipid-Based Drug Carrier Systems for Transdermal Delivery.

Transdermal delivery serves as non-invasive and effortless terminable means for systemic as well as topical drug delivery and finds itself as an option to conventional delivery route. Significant impervious nature of skin is the greatest hurdle for successful delivery of drug molecules to the deeper layers of skin for systemic absorption. Many approaches have been carried out for delivery of a medicament across skin barrier to enhance the efficacy. Among them lipid-based colloidal carriers have gained a unique position for transdermal delivery of drugs and bioactives owing to the presence of epidermal lipids as the chief component within the penetration barrier in high amount. Skin-carrier interaction involves attachment of these carriers to skin with a view to permit exchange of lipid between the outermost layers of the stratum corneum. Based on extensive literature search, although numerous reviews are available on lipid-based systems, but none of them relates exclusively to their transdermal uptake and toxicity. This review specifically focuses on the hurdles of transdermal drug delivery, role of lipid vehicular systems in transdermal drug delivery, uptake pathways, sequential uptake mechanism and cytotoxicity issues of lipid-based carriers which although considered safe, are not completely free from toxicity.