Lipid-based Drug Delivery Systems Research Articles

Effect of Rosa damascena Essential Oil Loaded in Nanostructured Lipid Carriers on the Proliferation of Human Breast Cancer Cell Line MDA-MB-231 in Comparison with Cisplatin

PurposeAs Rosa damascena essential oils (RDEOs) have antioxidant, antibacterial, antiviral, and insecticidal activity, they could therefore be useful in the treatment of breast cancer. In the current study, an attempt was made to incorporate RDEO in a lipid-based drug delivery system, namely, nanostructured lipid carrier (NLC) to boost its anticancer effect compared to cisplatin.MethodsGas chromatography (GC) identified the chemical compositions of RDEO. RDEO-NLCs were prepared using the probe ultrasonication method. The obtained nanoparticles were characterized in terms of particle size, polydispersity index, and zeta potential by dynamic light scattering. The encapsulation efficiency of the formulations and their loading capacity were also determined, and transmission electron microscopy (TEM) was employed to evaluate the morphology of the optimal formulation (quoted as RDEO-NLC2). The anticancer effect of RDEO-NLC2 on MDA-MB-231 cells and apoptosis were assessed using MTT and in vitro cellular assays respectively.ResultsTEM result revealed a distinct spherical shape for RDEO-NLC2, with an average particle size of 78.39 ± 1.5 nm obtained by Zetasizer. The results also showed that the obtained particles had a negative surface charge (− 31.0 mV) with a polydispersity index of 0.28 ± 0.01. The chemotherapy drug cisplatin showed more cytotoxicity than RDEO-NLC2 against cancer cells. Cellular data demonstrated that RDEO-NLC2 like cisplatin can decline the viability of MDA-MB-231 cells through apoptosis compared to cells treated with the placebo and free RDEO.ConclusionRDEO-NLC2 has the ability to stimulate apoptosis in the human BC cell line MDA-MN-231; hence, it can be beneficial in the treatment of patients suffering from breast cancer.

A Review on Innovative Drug Delivery Platforms

In recent years, the field of drug delivery has undergone a transformative shift with the introduction of innovative platforms that transcend conventional methods, providing accurate and efficient means for delivering therapeutic agents. This exploration delves into the distinctive features and potential impacts of these pioneering platforms, charting a course for the future of pharmaceutical interventions. In this review article, the advancements regarding the nanotechnology-enabled delivery, lipid-based drug delivery systems, targeted drug delivery, implantable drug delivery systems, 3D printing in drug delivery, stimuli-responsive delivery systems, mRNA and gene delivery platforms and microfluidic - based delivery systems were discussed. These innovative drug delivery platforms represent a dynamic frontier in pharmaceutical research and development. They afford unprecedented control over drug properties, release kinetics and targeting strategies. As research continues to push the boundaries of drug delivery science, these innovations hold the potential to revolutionize the treatment of various diseases, ushering in safer, more effective and patient-centric therapeutic solutions.

Re-engineering lysozyme solubility and activity through surfactant complexation

Hydrophobic ion-pairing is an established solubility engineering technique that uses amphiphilic surfactants to modulate drug lipophilicity and facilitate encapsulation in polymeric and lipid-based drug delivery systems. For proteins, surfactant complexation...

How do lipid-based drug delivery systems affect the pharmacokinetic and tissue distribution of amiodarone? A comparative study of liposomes, solid lipid nanoparticles, and nanoemulsions.

Lipid-based drug delivery systems (DDS) can improve the pharmacokinetic (PK) parameters of some drugs. Especially those with a high volume of distribution (Vd) leading to off-target accumulation and toxicity. Amiodarone as an anti-arrhythmic agent induces hypothyroidism and liver disorders limiting its clinical indication. In the present study, amiodarone PK parameters and biodistribution after IV administration of four nano-formulations to rats were compared. The formulations were liposomes, solid lipid nanoparticles (SLN), PEGylated SLN (PEG-SLN), and nanoemulsions (NE). All formulations were optimized. The nanoparticles were spherical with a diameter of 100-200 nm and sustained in vitro drug release in buffer pH 7.4. The best-fitted model for the plasma concentration-time profile was two-compartmental. In vivo studies indicated the most changes in PKs induced after liposome, SLN, and NE administration, respectively. The area under the curve (AUC) and maximum plasma concentration (Cmax) of liposomes, SLN, and NE were 22.5, 2.6, 2.46 times, and 916, 58, and 26 times higher than that of amiodarone solution, respectively (P-value<0.05). The heart-to-liver ratio of amiodarone was higher for nano-formulations compared to drug solution except for liposomes. Lipid-based particles can improve the PK parameters of amiodarone and its distribution in different tissues.

Itraconazole Self-Nano Emusifying Drug Delivery System for Enhancement of Solubility

The main objective of formulation is to enhance the bioavailability of the drug within the body. Some of the challenging subjects associated with poorly water-soluble drugs concern solubility and bioavailability factors. To overcome these problems, new technologies, such as lipid-based drug delivery systems including micro or nano emulsifying drug delivery system, have obtained importance in recent years, due to their enhanced solubility and bioavailability in the gastrointestinal tract. Such systems are solubilized within the lipid excipients or mixed with oils or surfactants/co-solvents to facilitate the solubility and absorption rate, which can enhance the bioavailability of the targeted drug. The research was targeted to develop a self-Nano Emulsifying drug delivery system (SNEDDS) for oral bioavailability enhancement of BCS II antifungal drug Itraconazole. Nano Emulsions are consignment methods that improve the solubility and distribution of lipid medicines to the intended areas. SNEDDS of Itraconazole were developed using Castor oil, Tween 20 as surfactant and PEG 200 as co-surfactant. SNEDDS formulation can be obtained through phase diagram approach. Pseudo Ternary phase diagrams were constructed, using Chemix software, to optimize the concentrations of excipients. Thermodynamic stability studies were satisfactory. Robustness to dilution did not exhibit phase separation and drug precipitation. The Among 4 formulations, B1F3 formulation showed more than 95% of drug content and were considered superior and subjected to droplet size analysis and zeta potential measurement. Droplet size ranged from 120 nm to 505 nm. The Nano size was obtained for formulation. The zeta-potential results indicated the range -35 mV. Based on all evaluation tests, formulation B2F3 was chosen as the best. Thus, this self-Nano Emulsifying drug delivery system should be an effective oral dosage form for improving oral bioavailability of lipophilic drug Itraconazole.

Transferosomes-A Novel Carrier for Drug Delivery

Transferosomes are a type of lipid-based drug delivery system that is designed to enhance the delivery of drugs through the skin or other biological barriers. They are composed of phospholipids, surfactants, and sometimes cholesterol, which form a bilayer structure that encapsulates the drug. Additionally, transferosomes can be tailored to target specific tissues or cells, which can increase the efficacy of drugs while reducing the risk of side effects. For example, transferosomes can be designed to deliver drugs to cancer cells, allowing for targeted cancer therapy with fewer side effects than traditional chemotherapy. In this article detailed discussion was made on formulation and applications of transferosomes.

Self-Nano Emulsifying Drug Delivery System: A Potential Solution to the Challenges of Oral Delivery of Poorly Water-Soluble Drugs

Lipid-based drug delivery systems (LBDDS) are the most promising technique to formulate the poorly water soluble drugs. Nanotechnology strongly influences the therapeutic performance of hydrophobic drugs and has become an essential approach in drug delivery research. Self-Nanoemulsifying drug delivery systems (SNEDDS) are a vital strategy that combines benefits of LBDDS and nanotechnology. SNEDDS are now preferred to improve the formulation of drugs with poor aqueous solubility. SNEDDS are isotropic mixtures composed of oils, surfactants, and occasionally cosolvents. The ability of these formulations and methods to produce nanoemulsions or fine oil-in-water (o/w) emulsions after moderate stirring and dilution by water phase along the GI tract. SNEDDS has garnered attention during recent years as it improves oral bioavailability, reduces drug dose, and increases drug protection from unsuitable environment in the gastrointestinal tract. It can solve the problems related to the dissolution and bioavailability of the Biopharmaceutics Classifcation System Class II and IV drugs. This review shortly describes the ambiguity between nanoemulsions and microemulsions, mechanism of self-emulsifications, composition and function of various excipients of SNEDDS. This review discusses characterization of SNEDDS, advantage of SNEEDS over other emulsion, biopharmaceutical aspects, and limitation as well as future views. The SNEDDS is a potential formulation for drug delivery. Owing to its small particle size, large surface area, high encapsulation efficiency, and high drug loading, the SNEDDS can improve the rate and extent of oral absorption by maximizing drug solubility in the intestinal absorption site. Moreover, because of the lipid-based formulation of SNEDDS, it can stimulate and enhance lymphatic transport of drugs to avoid hepatic first-pass metabolism, and thus improve their bioavailability.

Lipid-Based Nanoparticles as Oral Drug Delivery Systems: Overcoming Poor Gastrointestinal Absorption and Enhancing Bioavailability of Peptide and Protein Therapeutics.

Delivery and formulation of oral peptide and protein therapeutics have always been a challenge for the pharmaceutical industry. The oral bioavailability of peptide and protein therapeutics mainly relies on their gastrointestinal solubility and permeability which are affected by their poor membrane penetration, high molecular weight and proteolytic (chemical and enzymatic) degradation resulting in limited delivery and therapeutic efficacy. The present review article highlights the challenges and limitations of oral delivery of peptide and protein therapeutics focusing on the application, potential and importance of solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) as lipid-based drug delivery systems (LBDDSs) and their advantages and drawbacks. LBDDSs, due to their lipid-based matrix can encapsulate both lipophilic and hydrophilic drugs, and by reducing the first-pass effect and avoiding proteolytic degradation offer improved drug stability, dissolution rate, absorption, bioavailability and controlled drug release. Furthermore, their small size, high surface area and surface modification increase their mucosal adhesion, tissue-targeted distribution, physiological function and half-life. Properties such as simple preparation, high-scale manufacturing, biodegradability, biocompatibility, prolonged half-life, lower toxicity, lower adverse effects, lipid-based structure, higher drug encapsulation rate and various drug release profile compared to other similar carrier systems makes LBDDSs a promising drug delivery system (DDS). Nevertheless, undesired physicochemical features of peptide and protein drug development and discovery such as plasma stability, membrane permeability and circulation half-life remain a serious challenge which should be addressed in future.

Novel lipid-based nanocarrier of nitrofurantoin for improved oral bioavailability and reduced variability in absorption

The current research aims to improve oral bioavailability, reduce the variability in absorption, and decrease GI intolerance of Nitrofurantoin (NFT) by presenting in a lipid-based liquid self-nanoemulsifying drug delivery system (L-SNEDDS). L-SNEDDS formulations were developed using a thermosolvency technique. Physicochemical properties including in-vitro drug diffusion were exercised to optimize the formula, further, comparative ex-vivo permeability, in-vitro cell line, in-vitro anti-microbial, and in-vivo pharmacokinetic evaluation of optimized formulation was carried out. Based on the highest saturation solubility, soybean oil, oleoyl polyoxyl-6-glycerides, and diethylene glycol monoethyl ether were selected as oil, surfactant, and co-surfactant, respectively. A Smix ratio of 1:2 was selected based on pseudoternary phase diagrams. The formulation prepared with an equal ratio of oil and Smix exhibited the lowest globule size (59.4 ± 0.8 nm), optimum zeta potential (−21.3 ± 1.1 mV), and faster drug release (95.4 ± 4.2 % in 30 min), and hence was selected for further evaluation. Optimized formulation (SF5) was found stable and showed improved membrane permeability against pure drug suspension (1.84 times) and marketed suspension formulation (1.15 times). SF5 exhibited similar % cell viability and % cell toxicity in Caco-2 cell lines compared to the marketed suspension. However, it showed the highest zone of inhibition against both the gram-negative and gram-positive organisms. The relative bioavailability of NFT-loaded L-SNEDDS was enhanced by 1.46 and 1.55 times compared to the marketed and pure drug, respectively. Thus, it can be concluded that the variability of oral absorption is minimized, and oral bioavailability is improved by the novel lipid-based nanocarrier system of NFT.

The Development of Dermal Self-Double-Emulsifying Drug Delivery Systems: Preformulation Studies as the Keys to Success.

Self-emulsifying drug delivery systems (SEDDSs) are lipid-based systems that are superior to other lipid-based oral drug delivery systems in terms of providing drug protection against the gastrointestinal (GI) environment, inhibition of drug efflux as mediated by P-glycoprotein, enhanced lymphatic drug uptake, improved control over plasma concentration profiles of drugs, enhanced stability, and drug loading efficiency. Interest in dermal spontaneous emulsions has increased, given that systems have been reported to deliver drugs across mucus membranes, as well as the outermost layer of the skin into the underlying layers. The background and development of a double spontaneous emulsion incorporating four anti-tubercular drugs, clofazimine (CFZ), isoniazid (INH), pyrazinamide (PZY), and rifampicin (RIF), are described here. Our methods involved examination of oil miscibility, the construction of pseudoternary phase diagrams, the determination of self-emulsification performance and the emulsion stability index of primary emulsions (PEs), solubility, and isothermal micro calorimetry compatibility and examination of emulsions via microscopy. Overall, the potential of self-double-emulsifying drug delivery systems (SDEDDSs) as a dermal drug delivery vehicle is now demonstrated. The key to success here is the conduct of preformulation studies to enable the development of dermal SDEDDSs. To our knowledge, this work represents the first successful example of the production of SDEDDSs capable of incorporating four individual drugs.

Retraction note to: Treatment of methicillin resistant Staphylococcus aureus wound infection using vancomycin-loaded nanoparticles: An in vitro and in vivo study.

Due to the rise of bacteria that are resistant to multiple drugs, treating infections in burn wounds has become a worldwide problem. It is important to find new ways to treat these infections. Lipid-based drug delivery systems have emerged as a promising type of carrier for antibiotics as well as antibacterial agents, such as antimicrobial peptides and nucleic acids, for wound infections. To this end, the current study assessed the antibacterial effects and wound healing properties of vancomycin-loaded solid lipid nanoparticles (SLN) against methicillin-resistant Staphylococcus aureus (MRSA) surgical wound infections. vancomycin-SLN was synthesized by double emulsion solvent evaporation techniques, and then in vitro antibacterial activity was evaluated by well diffusion and broth microdilution methods. A surgical wound was inflicted on 36 male rats; the infection was caused by MRSA, and free vancomycin and vancomycin-SLN were topically applied. Particle size, PDI, zeta potential, drug loading, and encapsulation efficiency of the optimum vancomycin-SLN were 350 ± 24 nm, 0.402 ± 0.014, -16.3 ± 2.5 mV, 13.9 ± 1.4%, and 92.14 ± 3.1%, respectively. In vitro antibacterial assays showed lower MICs for free vancomycin and killed bacteria more efficiently than vancomycin-SLN. However, the synthesized nanoparticles indicated long-term antibacterial activity against MRSA. Animals that were treated with vancomycin-SLN showed the best wound healing procedure. Treatment of rats with vancomycin-SLN increased re-epithelialization and decreased granulation tissue development, as seen by histological analysis. Antibiotic-loaded SLN could not only manage wound infection but also enhance wound healing. Therefore, this kind of treatment should be considered by scientists as an applicable treatment for wounds.

Drug-Loaded Lipid Magnetic Nanoparticles for Combined Local Hyperthermia and Chemotherapy against Glioblastoma Multiforme.

Glioblastoma multiforme (GBM) is a devastating tumor of the central nervous system, currently missing an effective treatment. The therapeutic gold standard consists of surgical resection followed by chemotherapy (usually with temozolomide, TMZ) and/or radiotherapy. TMZ does not, however, provide significant survival benefit after completion of treatment because of development of chemoresistance and of heavy side effects of systemic administration. Improvement of conventional treatments and complementary therapies are urgently needed to increase patient survival and quality of life. Stimuli-responsive lipid-based drug delivery systems offer promising prospects to overcome the limitations of the current treatments. In this work, multifunctional lipid-based magnetic nanovectors functionalized with the peptide angiopep-2 and loaded with TMZ (Ang-TMZ-LMNVs) were tested to enhance specific GBM therapy on an in vivo model. Exposure to alternating magnetic fields (AMFs) enabled magnetic hyperthermia to be performed, that works in synergy with the chemotherapeutic agent. Studies on orthotopic human U-87 MG-Luc2 tumors in nude mice have shown that Ang-TMZ-LMNVs can accumulate and remain in the tumor after local administration without crossing over into healthy tissue, effectively suppressing tumor invasion and proliferation and significantly prolonging the median survival time when combined with the AMF stimulation. This powerful synergistic approach has proven to be a robust and versatile nanoplatform for an effective GBM treatment.

Application of Simplex Lattice Mixture design and desirability function in the development and Optimization of SEDDS for protein kinase inhibitor-Pazopanib Hydrochloride

Pazopanib Hydrochloride is a tyrosine protein kinase inhibitor molecule approved by USFDA and European agencies for the treatment of renal cell carcinoma (RCC) patients and other renal malignancies, but it has very poor aqueous solubility. Therefore, it is essential need to improve the solubility and in vitro dispersion or release characteristics. The purpose of this study was to investigate the Pazopanib hydrochloride drug solubility in various vehicles and screening of suitable solubilizers for the preparation of self-emulsifying lipid-based drug delivery systems (SE-LBDDS) of a poorly water-soluble drug (BCS class II), Pazopanib HCl by using simplex lattice mixture design. Ternaryplots wereconstructed by using oil (Labrafac WL 1349l), surfactant (Labrasol), and co-surfactant (Transcutol-P), and the concentration ranges were determined by using a simplex lattice design. The composition of pazopanib HCl SEEDS was optimized through various dependent variables (responses)such as solubility (Y1), precipitation after 15 min (Y2), and, particle size (Y3).Solubility study of pazopanib HCl in different oils, surfactants, and co-surfactants was carried out by shake flask method at 37°C. Three formulation components were chosen based on the maximum solubility results inthe oil, surfactant, and co-surfactant category and included in the experimental design. The results were analyzed by model fitting using the standard least-squares method. Pazopanib HCl were shown maximum solubility i.e. 25.64±0.24mg/g, 57.84 ±2.91mg/g and, 44.61±1.51mg/g in Labrafac WL 1349 (oil), Labrasol (surfactant) and Transcutol-P (co-surfactant) respectively. Hence these chosen formulation component's concentrations were further optimized by using a simplex lattice design (SLD). Derived mathematical polynomial equations and models were exercised to evaluate the impact of formulation input variables on the output variables (responses) using JMP software. The model p-value for both the responses i.e. solubility and particle size were found less than 0.05 hence models were significant. The results of the mathematical analysis demonstrated that the formulation components have a significant impact on the studied responses. Hence simplex lattice mixture design can be used as a powerful quality design to predict the optimized SEDDS formulation.The applicability of simplex lattice design with desirability function helped optimize a SEEDS formulation of pazopanib HCl and the selected model has made it possible to identify the impact of the critical factors to optimize the required responses.

When it is too much: Identifying butamben excess on the surface of pharmaceutical preformulation samples by Raman mapping

Butamben is a topical local anesthetic which formulation in lipid-based drug delivery systems (DDS) is challenging due to its affinity for hydrophilic excipients. This means that a medium polarity excipient is preferred for the development of a stable nanostructured lipid carrier (NLC) formulation. In turn, in NLC, the type and number of excipients will determine the active pharmaceutical ingredient (API) solubility and the maximum drug upload. To solve this dilemma and get the best formulation, a throughout screening study to evaluate API solubilization in different excipients was carried out. Subsequently, excipients with different solubilization capacities were selected for microscopic evaluation by Raman mapping, and in turn analysis of the distributional homogeneity index (DHI) and standard deviation of the histograms allowed solving the posed question. Design of experiments (DoE) was employed to understand better the interactions between the excipients; linear and higher-order models were obtained with R2 above of 0.8824. Even though DHI is a good parameter to be used as response, an API concentration higher than 30% (w/w) provided a homogeneous surface in case of good miscibility and, in this case, this parameter needs to be employed with an inspection and/or evaluation of other parameters. A curve of concentration vs. mean scores of images proved to be an alternative to identify the saturation/limit of linear range.

Gatifloxacin Loaded Nano Lipid Carriers for the Management of Bacterial Conjunctivitis.

Bacterial conjunctivitis (BC) entails inflammation of the ocular mucous membrane. Early effective treatment of BC can prevent the spread of the infection to the intraocular tissues, which could lead to bacterial endophthalmitis or serious visual disability. In 2003, gatifloxacin (GTX) eyedrops were introduced as a new broad-spectrum fluoroquinolone to treat BC. Subsequently, GTX use was extended to other ocular bacterial infections. However, due to precorneal loss and poor ocular bioavailability, frequent administration of the commercial eyedrops is necessary, leading to poor patient compliance. Thus, the goal of the current investigation was to formulate GTX in a lipid-based drug delivery system to overcome the challenges with the existing marketed eyedrops and, thus, improve the management of bacterial conjunctivitis. GTX-NLCs and SLNs were formulated with a hot homogenization-probe sonication method. The lead GTX-NLC formulation was characterized and assessed for in vitro drug release, antimicrobial efficacy (against methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa), and ex vivo permeation. The lead formulation exhibited desired physicochemical characteristics, an extended release of GTX over a 12 h period, and was stable over three months at the three storage conditions (refrigerated, room temperature, and accelerated). The transcorneal flux and permeability of GTX from the GTX-NLC formulation were 5.5- and 6.0-fold higher in comparison to the commercial eyedrops and exhibited a similar in vitro antibacterial activity. Therefore, GTX-NLCs could serve as an alternative drug delivery platform to improve treatment outcomes in BC.

Lipid based drug delivery systems for oral, transdermal and parenteral delivery: Recent strategies for targeted delivery consistent with different clinical application

Lipid-based drug delivery systems (LBDDS) are valuable and biocompatible nano-carriers for the vehiculation and potential delivery of various hydrophilic, hydrophobic, or amphiphilic compounds. LBDDS have the advantage of targeted drug delivery, as free drugs may have poor targeting, higher systemic toxicity, and possibilities of drug resistance. There is various type of lipid carrier systems for drug delivery based on the properties of drugs and clinical applications; nanoemulsion, microemulsion, lipid vesicles, and lipid nanoparticles. The era of targeted drug delivery is advancing from the superficial convention vesicles to the second generation of LBDDS by modulating the surface chemistry through modifying/surface functionalizing the lipid layer composition. The surfaces of lipid vehicles have been modified with small molecules, antibodies, peptides, and enzymes for targeted drug delivery and reduced toxicity. In this regard, polyethylene glycosylation (PEGylation) on the lipid surface was the first novel approach that improves blood circulation time and curtails opsonin resistance and clearance. However, multi-drug and multi-receptor strategies in the targeted-liposomal approach may be an innovative pathway to overcoming drug resistance while treating certain tumors. Several second-generation conventional drug delivery systems among liposomal formulations are at various stages of clinical trials. This review recapitulates the types of lipid formulations, characterization, and their applications in clinical aspects. Additionally, discuss the strategies for enhancement of disease targeting by surface functionalization with various entities to improve the drug delivery system.

In Situ Monitoring of Drug Precipitation from Digesting Lipid Formulations Using Low-Frequency Raman Scattering Spectroscopy.

Low-frequency Raman spectroscopy (LFRS) is a valuable tool to detect the solid state of amorphous and crystalline drugs in solid dosage forms and the transformation of drugs between different polymorphic forms. It has also been applied to track the solubilisation of solid drugs as suspensions in milk and infant formula during in vitro digestion. This study reports the use of LFRS as an approach to probe drug precipitation from a lipid-based drug delivery system (medium-chain self-nanoemulsifying drug delivery system, MC-SNEDDS) during in vitro digestion. Upon lipolysis of the digestible components in MC-SNEDDS containing fenofibrate as a model drug, sharp phonon peaks appeared at the low-frequency Raman spectral region (<200 cm-1), indicating the precipitation of fenofibrate in a crystalline form from the formulation. Two multivariate data analysis approaches (principal component analysis and partial least squares discriminant analysis) and one univariate analysis approach (band ratios) were explored to track these spectral changes over time. The low-frequency Raman data produces results in good agreement with in situ small angle X-ray scattering (SAXS) measurements with all data analysis approaches used, whereas the mid-frequency Raman requires the use of PLS-DA to gain similar results. This suggests that LFRS can be used as a complementary, and potentially more accessible, technique to SAXS to determine the kinetics of drug precipitation from lipid-based formulations.

Poly(ethylene glycol)-b-poly(epsilon-caprolactone) nanoparticles as a platform for the improved oral delivery of cannabidiol.

Cannabidiol (CBD), a non-psychoactive constituent of Cannabis, has proven neuroprotective, anti-inflammatory and antioxidant properties though his therapeutic use, especially by the oral route, is still challenged by the poor aqueous solubility that results in low oral bioavailability. In this work, we investigate the encapsulation of CBD within nanoparticles of a highly hydrophobic poly(ethylene glycol)-b-poly(epsilon-caprolactone) block copolymer produced by a simple and reproducible nanoprecipitation method. The encapsulation efficiency is ~ 100% and the CBD loading 11% w/w (high performance liquid chromatography). CBD-loaded nanoparticles show a monomodal size distribution with sizes of up to 100nm (dynamic light scattering), a spherical morphology, and the absence of CBD crystals (high resolution-scanning electron microscopy and cryogenic-transmission electron microscopy) which is in line with a very efficient nanoencapsulation. Then, the CBD release profile from the nanoparticles is assessed under gastric- and intestine-like conditions. At pH 1.2, only 10% of the payload is released after 1h. Conversely, at pH 6.8, a release of 80% is recorded after 2h. Finally, theoral pharmacokinetics is investigated in rats and compared to a free CBD suspension. CBD-loaded nanoparticles lead to a statistically significant ~ 20-fold increase of themaximum drug concentration in plasma (Cmax) and a shortening of the time to the Cmax (tmax) from 4 to 0.3h, indicating a more complete and faster absorption than in free form. Moreover, the area-under-the-curve(AUC), a measure of oral bioavailability, increased by 14 times. Overall results highlight the promise of this simple, reproducible, and scalable nanotechnology strategy to improve the oral performance of CBD with respect to common oily formulations and/or lipid-based drug delivery systems associated with systemic adverse effects.

A CRITICAL REVIEW AND SIGNIFICANCE OF LIPID-BASED AYURVEDIC DOSAGE FORMS GHRITA AND TAILA: PART I-REVIEW AND STATUS

This review discusses in detail one of the oldest lipid-based dosage form, Sneha Kalpana as described in Ayurved, one of the ancient medical systems. Here the vital constituents of plants are extracted as assimilates in lipid forms, ghrit–the clarified butter or taila–the oil. These dosage forms are administered through different routes for specific therapeutic benefits varying from topical nourishment, anti-inflammatory activity, and healing of tissue systems or even to treat serious neuro-muscular or neurological conditions. This review highlights the basic concepts of Ayurved behind the drug delivery approach and provides details of different processes of preparation or manufacture. Lipid-based drug delivery systems (LBDDS) are one of the emerging technologies designed to address the challenges of solubility and bioavailability of poorly water-soluble ingredients. Understanding the principles behind the processes–the right amount of heat, time, and intensity is important for standardization to ensure the availability of bio constituents. Also, it is essential to understand the relevance of therapeutic principles behind these dosage forms to choose an appropriate technological adaptation for its optimum clinical effectiveness.

Insights of Lipid-Based Drug Delivery Systems with an Emphasis on Quality by Design

Lipid-based drug delivery systems offer several advantages and have wide solubility, permeation, and bioavailability enhancement applications. This review provides detailed information on the fabrication, application and aspects of QbD of various lipid-based vesicles. Most of the review studies focused on lipid-based vesicles without the QbD aspect. This review article covers all the lipid-based systems in escalating on the method of QbD, which enhances the bioavailability of active pharmaceutical ingredients in different formulation approaches. Among all the different available approaches towards formulation development, lipid-based drug delivery systems (LBDDS) have continually maintained the limelight on themselves. One of the reasons for the popularity of LBDDS is their ability to solve problems with poorly water-soluble drugs and their bioavailability. Several drugs' efficacy was improved by utilizing this type of delivery system. Vesosomes, Phytosomes, Solid Lipid Nanoparticles (SLNs), Nanostructured Lipid Carriers (NLCs), and Archaeosomes are novel lipid-based systems with unique applications in drug delivery. Hence, the present perspective is to review the various LBDDS approaches utilized to enhance the formulations' performance while dissecting the studies systematically to get a clear outline of various LBDD subsystems, their applications, methods of preparation, and the mechanism of drug delivery. In addition to this, the review also focuses on overcoming the lacunas of the past literature by making an attempt to identify Quality target product profile (QTPP), Critical quality attributes (CQAs) and applying them for the statistical design of experiments and continuous strategy by QbD at the same time harnessing their potential in risk assessment. Applying QbD in developing lipid-based drug delivery systems reduces the number of trials and yields a product with in-built quality as it deliberates various critical variables, process parameters, risk assessment, and control strategy in formulation development.