Delivery Of Hydrophobic Drugs Research Articles

Different Drug Mobilities in Hydrophobic Cavities of Host–Guest Complexes between β-Cyclodextrin and 5-Fluorouracil at Different Stoichiometries: A Molecular Dynamics Study in Water

Cyclodextrins (CDs) are cyclic oligosaccharides able to form noncovalent water-soluble complexes useful in many different applications for the solubilization, delivery, and greater bioavailability of hydrophobic drugs. The complexation of 5-fluorouracil (5-FU) with natural or synthetic cyclodextrins permits the solubilization of this poorly soluble anticancer drug. In this theoretical work, the complexes between β-CD and 5-FU are investigated using molecular mechanics (MM) and molecular dynamics (MD) simulations in water. The inclusion complexes are formed thanks to the favorable intermolecular interactions between β-CD and 5-FU. Both 1:1 and 1:2 β-CD/5-FU stoichiometries are investigated, providing insight into their interaction geometries and stability over time in water. In the 1:2 β-CD/5-FU complexes, the intermolecular interactions affect the drug’s mobility, suggesting a two-step release mechanism: a fast release for the more exposed and hydrated drug molecule, with greater freedom of movement near the β-CD rims, and a slow one for the less-hydrated and well-encapsulated and confined drug. MD simulations study the intermolecular interactions between drugs and specific carriers at the atomistic level, suggesting a possible release mechanism and highlighting the role of the impact of the drug concentration on the kinetics process in water. A comparison with experimental data in the literature provides further insights.

Hybrid Microneedle-Mediated Transdermal Delivery of Atorvastatin Calcium-Loaded Polymeric Micelles for Hyperlipidemia Therapy.

Hyperlipidemia has been a huge challenge to global health, leading to the cardiovascular disease, hypertension, and diabetes. Atorvastatin calcium (AC), a widely prescribed drug for hyperlipidemia, faces huge challenges with oral administration due to poor water solubility and hepatic first-pass effects, resulting in low therapeutic efficacy. In this work, we designed and developed a hybrid microneedle (MN) patch system constructed with soluble poly(vinyl alcohol) (PVA) and AC-loaded polymeric micelles (AC@PMs) for transdermal delivery of AC to enhance the hyperlipidemia therapy. We first prepared various AC@PM formulations self-assembled from mPEG-PLA and mPEG-PLA-PEG block copolymers using a dialysis method and evaluated the physicochemical properties in combination with experiment skills and dissipative particle dynamics (DPD) simulations. Then, we encapsulated the AC@PMs into the PVA MN patch using a micromold filling method, followed by characterizing the performances, especially the structural stability, mechanical performance, and biosafety. After conducting in vivo experiments using a hyperlipidemic rat model, our findings revealed that the hybrid microneedle-mediated administration exhibited superior therapeutic efficacy when compared to oral delivery methods. In summary, we have successfully developed a hybrid microneedle (MN) patch system that holds promising potential for the efficient transdermal delivery of hydrophobic drugs.

Nanosuspensions: A Novel Drug Delivery System

The current article cites the importance of the emerging and promising future of new age dosage form, ‘nano suspensions’. Particle size reduction, particularly nanonization, is a non-specific, universal approach to improve the bioavailability of poorly soluble drugs. The article emphasizes importance in the preparation, evaluation and the research work going on with various drugs and their appropriate applications. Nano suspensions have emerged as a promising strategy for the efficient delivery of hydrophobic drugs because of their versatile features and unique advantages. Techniques such as media milling and high-pressure homogenization have been used commercially for producing nano suspensions. The unique features of nano suspensions have enabled their use in various dosage forms, including specialized delivery systems such as mucoadhesive hydrogels. Rapid strides have been made in the delivery of nano suspensions by parenteral, peroral, ocular and pulmonary routes. Currently, efforts are being directed to extending their applications in site-specific drug delivery.

Development of xylan-coated acid-resistant micellar drug carriers for colon-targeted oral delivery

Oral delivery of hydrophobic drugs from the stomach through the colon has some requirements: (1) an acid-resistant carrier (2) a colon-specific drug release mechanism; and (3) an enhanced bioavailability. In this study, curcumin-loaded polymeric micelles with a xylan-based composite coating were designed and developed. For this purpose, a new synthesis method was used to precipitate xylan by concurrent chitosan polymerization at different xylan/chitosan ratios using a negatively charged crosslinking agent, TPP. The study was to provide the stability of the coated micellar structures in the stomach (low pH conditions) and their degradation in the colon (a natural environment of bacteria) to release the drug. It was observed that the coating successfully prevented early drug release up to 85%, depending on the fraction of xylan in the coating. The nanocarriers that first passed through the stomach conditions were incubated with a xylanolytic colonic bacterium (Bacteroides ovatus) to determine the bacterium-related release mechanism, which was around 27%. This shows the colon-specific release expectation of coated nanocarriers in the colon environment, with an additional benefit due to the degradation of xylan and an improvement in the colon environment by prebiotic activity.

Mix and Shake: A Mild Way to Drug-Loaded Lysozyme Nanoparticles.

Biocompatible nanoparticles as drug carriers can improve the therapeutic efficiency of hydrophobic drugs. However, the synthesis of biocompatible and biodegradable polymeric nanoparticles can be time-consuming and often involves toxic solvents. Here, a simple method for protein-based stable drug-loaded particles with a narrow polydispersity is introduced. In this process, lysozyme is mixed with hydrophobic drugs (curcumin, ellipticine, and dasatinib) and fructose to prepare lysozyme-based drug particles of around 150 nm in size. Fructose is mixed with the drug to generate nanoparticles that serve as templates for the lysozyme coating. The effect of lysozyme on the physicochemical properties of these nanoparticles is studied by transmission electron microscopy (TEM) and scattering techniques (e.g., dynamic light scattering (DLS) and small-angle X-ray scattering (SAXS)). We observed that lysozyme significantly stabilized the curcumin fructose particles for 7 days. Moreover, additional drugs, such as ellipticine and dasatinib, can be loaded to form dual-drug particles with narrow polydispersity and spherical morphology. The results also reveal that lysozyme dual ellipticine/dasatinib curcumin particles enhance the cytotoxicity and uptake on MCF-7 cells, RAW 264.7 cells, and U-87 MG cells due to the larger and rigid hydrophobic core. In summary, lysozyme in combination with fructose and curcumin can serve as a powerful combination to form protein-based stable particles for the delivery of hydrophobic drugs.

Crystallization Inhibition and Enhanced Release of Nobiletin in Supramolecular Peptide Assemblies

To address the challenges associated with the crystallization tendency of natural bioactive drugs, we propose a strategy for encapsulating a model hydrophobic medicine, Nobiletin (NOB), using the self-assembly system formed by a peptide amphiphile C16-KVK-CONH2 (KVK). The experimental results demonstrate that at low concentrations, KVK forms micelles that can effectively encapsulate NOB molecules and significantly inhibit their crystallization. As the concentration increases, KVK self-assembles into a fibrous hydrogel, further enhancing the inhibition of NOB crystallization. In vitro release experiments reveal that NOB encapsulated by KVK exhibits superior release performance. When compared to traditional surfactants, KVK demonstrates better inhibitory effects on NOB crystallization, maintaining stability over a prolonged period, indicating its potential for hydrophobic drug delivery applications.

Redox-Responsive Gold Nanoparticles Coated with Hyaluronic Acid and Folic Acid for Application in Targeting Anticancer Therapy.

Methotrexate (MTX) has poor water solubility and low bioavailability, and cancer cells can become resistant to it, which limits its safe delivery to tumor sites and reduces its clinical efficacy. Herein, we developed novel redox-responsive hybrid nanoparticles (NPs) from hyaluronic acid (HA) and 3-mercaptopropionic acid (MPA)-coated gold NPs (gold@MPA NPs), which were further conjugated with folic acid (FA). The design of FA-HA-ss-gold NPs aimed at enhancing cellular uptake specifically in cancer cells using an active FA/HA dual targeting strategy for enhanced tumor eradication. MTX was successfully encapsulated into FA-HA-ss-gold NPs, with drug encapsulation efficiency (EE) as high as >98.7%. The physicochemical properties of the NPs were investigated in terms of size, surface charges, wavelength reflectance, and chemical bonds. MTX was released in a sustained manner in glutathione (GSH). The cellular uptake experiments showed effective uptake of FA-HA-ss-gold over HA-ss-gold NPs in the deep tumor. Moreover, the release studies provided strong evidence that FA-HA-ss-gold NPs serve as GSH-responsive carriers. In vitro, anti-tumor activity tests showed that FA-HA-ss-gold/MTX NPs exhibited significantly higher cytotoxic activity against both human cervical cancer (HeLa) cells and breast cancer (BT-20) cells compared to gold only and HA-ss-gold/MTX NPs while being safe for human embryonic kidney (HEK-293) cells. Therefore, this present study suggests that FA-HA-ss-gold NPs are promising active targeting hybrid nanocarriers that are stable, controllable, biocompatible, biodegradable, and with enhanced cancer cell targetability for the safe delivery of hydrophobic anticancer drugs.

Spatiotemporally-controlled hydrophobic drug delivery via photosensitizer-driven assembly-disassembly for enhanced triple-negative breast cancer treatment

Therapeutic approaches for triple-negative breast cancer (TNBC) have been continuously advancing, but inadequate control over release behavior, insufficient tumor selectivity, and limited drug availability continue to impede therapeutic outcomes in nanodrug systems. In this study, we propose a general hydrophobic antineoplastic delivery system, termed spatiotemporally-controlled hydrophobic antineoplastic delivery system (SCHADS) for enhanced TNBC treatment. The key feature of SCHADS is the formation of metastable photosensitive-antineoplastic complexes (PACs) through the self-assembly of hydrophobic drugs driven by photosensitive molecules. With the further decoration of tumor-targeting peptides coupled with the EPR effect, the PACs tend to accumulate in the tumor site tremendously, promoting drug delivery efficiency. Meanwhile, the disassembly behavior of the metastable PACs could be driven by light on demand to achieve in situ drug release, thus promoting chemotherapeutics availability. Furthermore, the abundant ROS generated by the photosensitizer could effectively kill tumor cells, ultimately realizing an effective combination of photodynamic and chemotherapeutic therapy. As an exemplary presentation, chlorin e6 has been chosen to drive the formation of PACs with the system xc− inhibitor sorafenib. Compared with pure drug treatment, the PACs with the above-described preponderances exhibit superior therapeutic effects both in vitro and in vivo and circumvent the side effects due to off-target. By manipulating the laser irradiation, the PACs-treated cell death mechanism could be dynamically regulated, thus providing the potential to remedy intrinsic/acquired resistance of tumor. Collectively, this SCHADS achieves spatio-temporal control of the drug that greatly enhances the availability of anticarcinogen and realizes synergistic antitumor effect in TNBC treatment, even ultimately being extended to the treatment of other types of tumors.

Selective Anticervical Cancer Injectable and Self-Healable Hydrogel Platforms Constructed of Drug-Loaded Cross-Linkable Unimolecular Micelles in a Single and Combination Therapy.

In the face of severe side effects of systemic chemotherapy used in cervical cancer, topical selective drug carriers with long-lasting effects are being sought. Hydrogels are suitable platforms, but their use is problematic in the case of delivery of hydrophobic drugs with anticancer activity. Herein, hydrogels constructed of unimolecular micelles displaying enhanced solubilization of aromatic lipophilic bioactive compounds are presented. Star-shaped poly(benzyl glycidyl ether)-block-poly(glycidyl glycerol ether) with an aryl-enriched core show high encapsulation capacity of poor water-soluble nifuratel and clotrimazole. Nifuratel attained selectivity against cervical cancer cells, whereas clotrimazole preserved its original selectivity. The combination of unimolecular micelles loaded with both drugs provided synergism; however, they were still selective against cervical cancer cells. The cross-linking of drug-loaded unimolecular micelles via dynamic boronic esters provided injectable and self-healable hydrogel drug carriers also displaying synergistic anticancer activity, suitable for intravaginal administration and assuring the effective coverage of the afflicted tissue area and efficient tissue permeability with hydrophobic bioactive compounds. Here, we show that the combination of star-shaped polyether amphiphiles and boronic ester cross-linking chemistry provides a new strategy for obtaining hydrogel platforms suitable for efficient hydrophobic drug delivery.

Oral fast dissolving films for co-administration of breviscapine and matrine: Formulation optimization and in vitro characterization

Oral fast dissolving films (OFDFs) are popular dosage forms for enhanced oral absorption of active ingredients without experiencing gastrointestinal interference or first-pass metabolism. The primary challenge in OFDF design is balancing drug loading capacity with film properties, particularly for poorly soluble drugs. In the present work, an OFDF formulation containing co-amorphous mixture was successfully designed for co-administration of two natural products at a drug content of 14%. Breviscapine and matrine are commonly used for cardiovascular and cerebrovascular related diseases, but their clinical application was limited by low bioavailability, short biological half-life, and instability problems. Their co-administration as a compound remedy requires a novel product too enhance drug dissolution and patient compliance. A 33 Box-Behnken design was used to generate OFDF preparations by solvent casting method. The optimized blank film formulation, comprising 57.40% HPMC E50, 14.01% PEG 400 and 5.35% L-HPC, demonstrated a rapid disintegration in 18 s. XRD and FTIR analysis on drug-loaded films revealed good compatibility of drugs and polymers, and amorphous state of films with co-precipitates. The films were evaluated for morphology, folding endurance, disintegration time and in vitro BRE dissolution. Drugs incorporation extended the disintegration time of blank films, yet remained under 30 s. The co-amorphous mixture of BRE and MAT in films exhibited a faster BRE dissolution rate compared to the physical mixture. In conclusion, a compound OFDF formulation featuring a co-amorphous mixture of BRE and MAT offers an efficient strategy for hydrophobic drug delivery at high dose.

PNIPAm-Based pH and Thermoresponsive Copolymer Hydrogel for Hydrophobic and Hydrophilic Drug Delivery.

The regulated and targeted administration of hydrophobic and hydrophilic drugs is both promising and challenging in the field of drug delivery. Developing a hydrogel which is responsive to dual stimuli is considered a promising and exciting research area of study. In this work, melamine functionalized poly-N-isopropyl acrylamide-co-glycidyl methacrylate copolymer has been developed by copolymerizing glycidyl methacrylate (GMA) monomer with N-isopropyl acrylamide (NIPAm) and further functionalized with melamine units (pNIPAm-co-pGMA-Mela). The prepared pNIPAm-co-pGMA-Mela copolymer hydrogel was characterized using various characterization techniques, including 1H NMR, FTIR, SEM, zeta potential, and particle size analysis. A hydrophobic drug (ibuprofen, Ibu) and hydrophilic drug (5-fluorouracil, 5-Fu) were selected as model drugs. Dual pH and temperature stimuli-responsive drug release behavior of the pNIPAm-co-pGMA-Mela hydrogel was evaluated under different pH (pH 7.4 and 4.0) and temperature (25 °C, 37 °C, and 45 °C) conditions. Furthermore, the in vitro biocompatibility of the developed pNIPAm-co-pGMA-Mela copolymer hydrogel was determined on MDA-MB-231 cells. The pH and temperature-responsive drug delivery study results reveal that the pNIPAm-co-pGMA-Mela hydrogel system is responsive to both pH and temperature stimuli and exhibits about ~100% of Ibu and 5-Fu, respectively, released at pH 4.0/45 °C. Moreover, the MTT assay and hemocompatibility analysis results proved that the pNIPAm-co-pGMA-Mela hydrogel system is biocompatible and hemocompatible, suggesting that that it could be used for drug delivery applications. The experimental results suggest that the proposed pNIPAm-co-pGMA-Mela hydrogel system is responsive to dual pH and temperature stimuli, and could be a promising drug carrier system for both hydrophilic and hydrophobic drug delivery applications.

Improving oral absorption of tretinoin by ionic liquids technology

Oral delivery of the hydrophobic tretinoin (Tre) is a significant challenge due to poor solubility and bioavailability. Herein, we describe the potential of ionic liquids (ILs, e.g., [Ch][Ger]), in particular active pharmaceutical ingredient-based ILs (API-ILs, e.g., [Ch][Tre]) and their mixtures (e.g., [Ch][Tre]-[Ch][Ger]), for oral delivery of Tre. [Ch][Tre] provided excellent apparent content of Tre (42.10 g/mL), a 175 million-fold improvement over its water solubility. The cumulative Tre release at 5 min of Tre-[Ch][Ger] and [Ch][Tre]-[Ch][Ger] reached 95% and 97%, respectively. Upon the same oral dosing of Tre in rats, [Ch][Tre]-[Ch][Ger] increased peak blood concentration of Tre by 2.9-fold and total Tre exposure by 3.6-fold. Furthermore, the oral bioavailability of Tre in [Ch][Tre]-[Ch][Ger] was significantly enhanced to 361.4%. It's speculated that the mixture of ILs gave rise to sophisticated solvent structures, making the system more stable to enhance the drug adsorption. In conclusion, our findings highlight the potential of ILs technology as a promising platform for oral delivery of hydrophobic drugs.

Lauric acid-based thermosensitive delivery system for the treatment of head and neck squamous cell carcinoma

Traditional treatments for head and neck squamous cell carcinoma (HNSCC) such as surgery, radiation therapy, and chemotherapy, often have severe side effects. Local delivery of chemotherapeutic agents can be a promising approach to minimise systemic toxicity and improve efficacy. Lauric acid (LA), was explored as a novel injectable thermosensitive drug reservoir as a depot for sustained release of anticancer drugs to treat HNSCC. LA was characterised in terms of melting temperature and gelation time. The efficacy of LA-based drug formulations was tested in vitro in a HNSCC cell line and in vivo in a mouse model of HNSCC. LA was modified to have a melting point of 38.5 °C and a gelation time of 40 s at 37.5 °C, rendering it suitable for injection at body temperature. LA- based doxorubicin (DOXO) formulation showed slow release with a maximum of 18% release after 3 days. The in vitro study showed that LA enhanced the cytotoxic effect of DOXO. LA combined with DOXO prevented tumour progression and LA alone significantly reduced the original tumour volume compared to the untreated control group. These findings confirmed that LA can function as practical carrier for the local delivery of chemotherapeutics and provides a safe and simple strategy for the delivery of hydrophobic anticancer drugs and warrant further testing in clinical trials.

Synthesis and characterization of the redox-responsive amphiphilic fluorescent alginate derivatives as the multi-functional hydrophobic anticancer drug delivery system with visualization and sustained release

To develop the multi-functional hydrophobic anticancer drug carriers with visualization and sustained release, a novel amphiphilic alginate derivative (LSA-SS-DEAC) containing chromophobe groups was designed and synthesized by grafting hydrophobic fluorescent molecule, 7-(diethylamino-coumarin-3-carboxylic acid (DEAC-COOH) onto hydrophilic low molecular alginate backbone through cystamine by water-soluble carbodiimide chemical method. The molecular structure and self-assembly properties of the synthesized LSA-SS-DEAC were characterized. Furthermore, the encapsulation of anti-cancer drugs, doxorubicin hydrochloride (DOX) in LSA-SS-DEAC self-assembled micelles was realized by ultrasonic dialysis method. Subsequently, the in vitro drug release behavior and in vitro cytotoxicity of LSA-SS-DEAC micelles in simulated tumor microenvironment were also studied. The resultant LSA-SS-DEAC with the critical micelle concentration (CMC) of 0.26 mg/mL exhibited the ability to spontaneously form spherical micelles with the particle size of 250.2 ± 4.3 nm (PDI = 0.23) and zeta potential of −49.1 ± 0.4 mV, which presented good stability in pH 7.4 PBS and excellent fluorescence properties and redox responsiveness. The drug-loaded LSA-SS-DEAC micelles had the optimal EE value of about 42.2% when the DOX/LSA-SS-DEAC mass ratio was 3:10. Meanwhile, The drug-loaded LSA-SS-DEAC micelles exhibited sustained release in GSH-free environment, and the cumulative drug release rates were 40.3% and 46.6% in pH 7.4 and 5.0 PBS for 48 h, respectively. However, in the simulated tumor cell microenvironment (pH 5.0 PBS + 10 mM GSH), the disulfide bond between the core-shell was broken under the GSH trigger, and the LSA-SS-DEAC micelles collapsed, resulting in a cumulative drug release rate of about 64% at 12 h. In vitro cytotoxicity results showed that LSA-SS-DEAC had low cytotoxicity, and revealed obvious inhibitory effect on HeLa cells after DOX loading. Fluorescence imaging results indicated that LSA-SS-DEAC micelles could emit green light after ingested by cells, and their fluorescence properties were not affected after encapsulation of DOX. Accordingly, LSA-SS-DEAC micelles had the potential for drug localization tracking and rapid drug release at focal sites, which could be expected to be an ideal drug carriers for hydrophobic anticancer drug delivery.

Teaching an Old Dog New Tricks: A Global Approach to Enhancing the Cytotoxicity of Drug-Loaded, Non-responsive Micelles Using Oligoelectrolytes.

Polymeric micelles have been extensively studied as vectors for the delivery of hydrophobic drugs for the treatment of cancers and other diseases. Despite intensive research, few formulations provide significant benefits, and even fewer have been clinically approved. While many traditional non-responsive micelles have excellent safety profiles, they lack the ability to respond to the intracellular environment and release their cargo in a spatiotemporally defined manner to effectively deliver large doses of cytotoxic drugs into the cytosol of cells that overwhelm efflux pumps. As a novel and adaptable strategy, we hypothesized that well-established non-responsive polymeric micelles could be augmented with a pH-trigger via the co-encapsulation of cytocompatible oligoelectrolytes, which would allow rapid cargo release in the endosome, leading to increased cytotoxicity. Herein, we demonstrate how this strategy can be applied to render non-responsive micelles pH-responsive, resulting in abrupt cargo release at specific and tunable pH values compatible with endosomal delivery, which significantly increased their cytotoxicity up to 3-fold in an ovarian adenocarcinoma (SKOV-3) cell line compared to non-responsive micelles. In comparison, the oligoelectrolyte-loaded micelles were significantly less toxic to healthy 3T3 fibroblasts, indicating a selective cargo release in cancer cell lines. Oligoelectrolytes can be co-encapsulated in the micelles along with drugs at high encapsulation efficiency percentages, which are both ejected from the micelle core upon oligoelectrolyte ionization. Mechanistically, the increase in cytotoxicity appears to also result from the accelerated endosomal escape of the cargo caused by disruption of the endosomal membrane by the simultaneous release of the oligoelectrolytes from the micelles. Furthermore, we show how this approach is broadly applicable to non-responsive micelles regardless of their composition and various classes of hydrophobic chemotherapeutics. The preliminary studies presented here reveal the versatility and wide scope of oligoelectrolyte-mediated, pH-triggered drug release as a compelling and powerful strategy to enhance the cytotoxicity of non-responsive polymeric micelles.

Solid dispersions of bedaquiline fumarate to improve its pharmaceutical attributes: A comparative study between PEG and PVP

ObjectivesThe therapeutic delivery of hydrophobic drugs via solid dispersion is an appealing methodology to enhance the dissolution rate and ultimately the in vivo bioavailability. The objective of current investigation was to enhance the solubility of anti-tubercular drug bedaquiline fumarate (BQF) via solid dispersion strategy, where the influence of polyethylene glycol and polyvinylpyrrolidone on the performance of solid dispersions was determined. MethodsBQF-solid dispersions with polyethylene glycol and polyvinylpyrrolidone were fabricated via solvent evaporation technique and evaluated for solubility, in vitro dissolution studies, cytotoxicity, cellular uptake, intestinal permeability, and pharmacokinetics. ResultsSolubility of BQF was improved by 6.4-fold and 13.44-fold with polyethylene glycol and polyvinylpyrrolidone-based ternary solid dispersions, respectively. The in vitro dissolution studies revealed significant enhancement in dissolution rate of BQF. The in vivo pharmacokinetic results demonstrated that solid dispersions significantly improved the pharmacokinetic parameters of BQF. The relative bioavailability of BQF with polyvinylpyrrolidone-based ternary solid dispersion was found to be enhanced by 173% and 154%, under fasted and fed state, respectively, when compared to BQF suspension. ConclusionsOur study reaffirms the applicability of solid dispersions as an alternative formulation strategy to improve the biopharmaceutical attributes of BQF in tuberculosis therapy.

Emulgel: A Cutting Edge Approach for Topical Drug Delivery System.

Emulgel is considered an advanced leading form of topical drug delivery system. It possesses the quality of a dual control drug mechanism for drug release as it holds the properties of both gel as well as emulsion. Emulgel is capable of overcoming the problems of the conventional route of topical drug delivery, like low spreadability and stickiness with the delivery of hydrophobic drugs, enhanced bioavailability at the local site of action, no greasy texture, and ensuring patient compliance. An emulsion is used either w/o or o/w, and the drug can be incorporated into the suitable phase of the emulsion. After that, the emulsion is incorporated into the gel phase. Several factors like oil phase, gelling agent, and emulsifier can affect the efficacy and stability. This advancement is beneficial not only for dermatology but also for cosmetology as well. Currently, emulgel-based formulations are used for the delivery of anti-inflammatory, analgesic, anti-acne, and antifungal drugs with a wide array of exploration.

Alginate hydrogel incorporating cellulose nanofiber from solid waste agar industry for hydrophobic antibiotic delivery: Synthesis and characterization

Undoubtedly, there is an increasing inclination towards the development of hydrogels derived from natural sources for the purpose of delivering hydrophobic antibiotics. In this study, alginate hydrogels containing cellulose nanofibrils (CNF) were synthesized from solid waste agar industry (SWAI) via Hydrated deep eutectic solvent (DES) hydrolysis and mechanical treatment, intending to encapsulate chloramphenicol and examine the properties of the alginate-CNF (ALG-CNF) hydrogel at various CNF concentrations. The CNF displays a fibrous morphology, surface charge of − 39.3 ± 0.3 mV, 62.95% crystallinity, and type-I cellulose. The incorporation of CNF notably affected the characteristics of the ALG-CNF hydrogel. Chloramphenicol was effectively encapsulated within the ALG-CNF hydrogel matrix. Chloramphenicol release showed a biphasic profile, with controlled release occurring within 48 h. The drug release kinetics adhered to the Korsmeyer-Peppas model, reflecting pseudo-Fickian diffusion (n < 0.45), with a high determination coefficient (R² ≈ 0.95). Antibacterial susceptibility tests demonstrated that ALG-CNF hydrogels inhibited the growth of E. coli, S. aureus, and P. aeruginosa. The ALG-CNF hydrogel demonstrated favorable physical properties, drug release, and antibacterial properties, making it a prospective candidate for future studies on wound dressings and hydrophobic drug delivery systems.

Data-driven development of an oral lipid-based nanoparticle formulation of a hydrophobic drug.

Due to its cost-effectiveness, convenience, and high patient adherence, oral drug administration normally remains the preferred approach. Yet, the effective delivery of hydrophobic drugs via the oral route is often hindered by their limited water solubility and first-pass metabolism. To mitigate these challenges, advanced delivery systems such as solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) have been developed to encapsulate hydrophobic drugs and enhance their bioavailability. However, traditional design methodologies for these complex formulations often present intricate challenges because they are restricted to a relatively narrow design space. Here, we present a data-driven approach for the accelerated design of SLNs/NLCs encapsulating a model hydrophobic drug, cannabidiol, that combines experimental automation and machine learning. A small subset of formulations, comprising 10% of all formulations in the design space, was prepared in-house, leveraging miniaturized experimental automation to improve throughput and decrease the quantity of drug and materials required. Machine learning models were then trained on the data generated from these formulations and used to predict properties of all SLNs/NLCs within this design space (i.e., 1215 formulations). Notably, formulations predicted to be high-performers via this approach were confirmed to significantly enhance the solubility of the drug by up to 3000-fold and prevented degradation of drug. Moreover, the high-performance formulations significantly enhanced the oral bioavailability of the drug compared to both its free form and an over-the-counter version. Furthermore, this bioavailability matched that of a formulation equivalent in composition to the FDA-approved product, Epidiolex®.

Antibacterial Drug Development Using Starch Nanoparticles

Abstract: The naturally available carbohydrate polymer, starch, is biodegradable and biocompatible, making it suitable for drug encapsulation due to the presence of various hydroxy functionalities. Multidrug resistance in antibacterial agents can sometimes limit their use and pose toxicity issues due to dose-related problems resulting from the low bioavailability or solubility of hydrophobic drugs. To address this issue, antibiotics are delivered using nanocarriers that protect therapeutic agents from degradation and enhance the delivery of hydrophobic drugs. This review article discusses the utilization of starch nanoparticles as drug delivery vehicles or carriers for antibacterial agents.