Effects of a Sheer 100% Mineral Sunscreen Moisturizer on Facial Photodamage Across Fitzpatrick Skin Types.

BACKGROUND: All skin tones need to be protected from the damaging effects of solar radiation. Although mineral sunscreens offer protection, they can have a thick, greasy feel and leave a white cast, particularly on darker skin tones. Tints offset white cast and provide visible light protection; however, patients may prefer a sheer option. Therefore, a multifunctional, sheer, 100% mineral sunscreen moisturizer (MSM) with broad-spectrum SPF 50 was developed to have positive aesthetics and deliver anti-aging and skin health benefits to all skin tones.  Methods: An IRB-approved, 12-week, open-label clinical study was conducted to investigate the efficacy and tolerability of the MSM. Thirty-nine (39) females aged 35 to 60 years with moderate-severe overall facial photodamage and representing all Fitzpatrick skin types (FST) were recruited. Participants applied the MSM to the face and neck in the morning and reapplied per US Food and Drug Administration requirements. Efficacy and tolerability grading, photography, ultrasound imaging, corneometer measurements, and questionnaires were completed at baseline and weeks 4, 8, and 12.  Results: Statistically significant progressive improvements were demonstrated from baseline to week 12. At week 12, 23.4% and 26.5% mean improvements in overall photodamage were seen for FST I-III and FST IV-VI, respectively. Favorable tolerability was shown for both the face and neck. Photography corroborated clinical grading, and ultrasound imaging indicated a trend in skin density improvement. The MSM was well-perceived.  Conclusion: The MSM is an efficacious and well-tolerated product for patients of all skin tones who desire a sheer, 100% mineral sunscreen moisturizer with anti-aging and skin health benefits. J Drugs Dermatol. 2024;23(7):538-544.  doi:10.36849/JDD.8082.

Long-Term Efficacy and Tolerability of a Daily Serum for Rejuvenation and Prejuvenation of Facial Skin.

Onjectives: To evaluate the long-term efficacy and tolerance of an anti-aging daily serum (AADS) when used twice-daily over 12 weeks by women with moderate skin fatigue and overall photodamage. The treatment targeted rejuvenation and prejuvenation of the facial skin. Method: This was an institutional review board (IRB)-approved, randomized, single-center, double-blinded, vehicle-controlled (VC) study involving healthy subjects. Seventy female subjects were recruited aged 30 to 60 years old, Fitzpatrick skin types I to VI, with moderate overall photodamage, facial skin dullness, and skin firmness. Subjects underwent a 1-week washout period with a skincare regimen consisting of a cleanser, moisturizer, and sunscreen. Subjects were randomized to apply the AADS or VC to their face including upper eyelid, twice-daily for 12 weeks. Long-term efficacy and tolerance, self-assessment questionnaire, and VISIA® clinical photography were performed at baseline, weeks 4, 8, and 12.  Results: Statistically significant improvements in live, clinically graded efficacy parameters were demonstrated at post-baseline timepoints. Facial skin firmness, radiance, and roughness showed the most significant improvements at week 12. Analysis between treatments, in both live and photo-graded parameters, demonstrated merit of the AADS. VISIA® analysis further substantiated the efficacy of the AADS vs the VC. The AADS was well tolerated by clinical scoring and rating by subjects.  Conclusion: The AADS is effective in improving skin fatigue and overall photodamage after 12 weeks of twice-daily application compared with the VC. The AADS is a possible skincare solution for patients seeking a serum with skin rejuvenation and prejuvenation benefits. Citation: Reid L, Palm MD, Kononov T, et al. Long-term efficacy and tolerability of a daily serum for rejuvenation and prejuvenation of facial skin. J Drugs Dermatol. 2023;22(9):917-924. doi:10.36849/JDD.7393.

A multi-functional anti-aging moisturizer maintains a diverse and balanced facial skin microbiome.

AIMS: To assess the effect of a 28-day skincare regimen in healthy female subjects on the facial skin microbiome composition and to determine whether the skincare regimen including a gentle cleansing lotion, a multi-functional anti-aging moisturizer formulated with prebiotics and postbiotics at skin neutral pH, and bland sunscreen pushed the microbiome to a healthier state and improved skin aging measured by self-assessment and clinical photography. METHODS AND RESULTS: The study protocol was in accordance with the EU Scientific Committee on Consumer Safety (SCCS) guidance and met all international standards. In all, 25 female subjects between 35 and 65 years old with Fitzpatrick skin types I-VI, moderate crow's feet wrinkles and global face photodamage were enrolled. After 28 days, the skincare regimen improved microbial facial diversity and shifted the microbiota composition when compared to baseline. CONCLUSIONS: After 28 days, the skincare regimen treatment shifted the distribution of the facial skin microbiome, positively influencing the skin microbiome diversity and balance, to promote long-term skin health and protect from further skin aging. SIGNIFICANCE AND IMPACT OF THE STUDY: These results suggest that incorporating prebiotics and postbiotics into a skincare regimen may have a positive impact on the facial skin microbiome in healthy women.

A Randomized, Double-Blind, Split-Body, Placebo-Controlled Clinical Study to Evaluate the Efficacy and Tolerability of a Topical Body Firming Moisturizer for Upper Arm Rejuvenation.

BACKGROUND: Aging of upper arm skin, induced by intrinsic and extrinsic factors, often results in a loss of contour, elasticity, and firmness, and an increase in laxity, crepiness, roughness, and photodamage. A topical body firming moisturizer (TBFM) was developed to target all aspects of skin aging. OBJECTIVES: The aim of this study was to evaluate the efficacy and tolerability of the TBFM for upper arm firming and rejuvenation. METHODS: Forty female subjects, 40 to 60 years old, Fitzpatrick skin type II to V, with mild to moderate laxity, crepiness, and photodamage on the upper arms, were recruited into the study, 10 of whom were selected for biopsy analysis. Subjects were randomly allocated to apply the TBFM and placebo moisturizer on the assigned arms twice daily for 12 weeks. At each visit, efficacy and tolerability evaluation, self-assessment, and standardized clinical photography were performed. Ultrasound measurements were performed at baseline, week 8 and week 12. RESULTS: Efficacy evaluation by a clinical grader and bioinstrumentation analysis showed the TBFM improved all skin parameters of the aged upper arm while outperforming the placebo moisturizer after 12 weeks. Clinical photography showed the test product toned and firmed the skin. The TBFM was well tolerated and well perceived by the subjects. Ultrasound images indicated an improvement in skin density and skin structure at week 12. CONCLUSIONS: This clinical trial indicates that the TBFM was well tolerated and was effective in improving crepey, lax, and photodamaged skin of the upper arms after 12 weeks of treatment twice daily.

Effectiveness and tolerance of multicorrective topical treatment for infraorbital dark circles and puffiness.

BACKGROUND: Treatment of infraorbital dark circles and under-eye puffiness is challenging due to its multifactorial nature and lack of broadly applicable, effective treatments. A daily skincare treatment option that is multimodal, effective, and tolerable across a broad patient population is an unmet need. AIM: A multicorrective topical eye cream (MTEC) formulated with Tetrahexyldecyl (THD) ascorbate (vitamin C), prebiotic Inula Helenium, bioavailable peptides, botanical extracts, chrysin, and caffeine is hypothesized to improve the appearance of infraorbital dark circles and under-eye puffiness by targeting microvasculature congestion and permeability, melanin accumulation and hemoglobin degradation-related pigmentation, and skin health. METHODS: An IRB approved, open-label, 12-week clinical study set out to evaluate the efficacy and tolerability of the MTEC across a broad patient population including varying ethnicities and Fitzpatrick Skin Types (FST). Female subjects (n = 40) ages 35-60 years old, with moderate-to-severe under-eye dark circles, moderate under-eye puffiness, and mild-to-moderate fine lines were enrolled into the study. Objective (Chromameter, VISIA® imaging, and Laser Doppler) and subjective assessments (clinical grading and self-assessment questionnaire) were conducted at baseline and post-baseline timepoints. RESULTS: Thirty-seven subjects completed the study, and the MTEC efficaciously demonstrated short-term and long-term improvements in objective and subjective assessments across a broad patient population. Specifically, the MTEC demonstrated significant improvement of infraorbital dark circles, mainly by the reduction in microvasculature congestion and permeability, melanin, and hemoglobin degradation-related pigmentation. CONCLUSION: Topical application of the MTEC may offer an effective and tolerable treatment option for infraorbital dark circles and puffiness.

A Rejuvenating treatment targeting "tech neck" lines and wrinkles in Chinese women: A prospective, open-label, single-center study.

BACKGROUND: Aging of neck and jawline skin is caused by intrinsic and extrinsic factors and is evidenced by wrinkling, laxity, skin dyspigmentation, loss of the mandibular contour, accumulation of submental fat, density loss, and prominent platysma bands. Early intervention with topical cosmeceuticals, especially in younger subjects with "tech neck," can offer a solution and potentially mitigate aging of the neck and jawline. AIM: The objective of this prospective, open-label, single-center clinical study was to assess the efficacy and tolerability of a topical anti-aging neck treatment (TNT) in a cohort of Chinese women with mild to moderate signs of aging on the neck and jawline. SUBJECTS/METHODS: This study was approved by an ethics committee and involved healthy Chinese subjects. Thirty-five female subjects, 25-50 years old, with mild to moderate signs of aging of the neck and jawline were recruited. Subjects applied the TNT to the neck and jawline twice daily for 84 days. Long-term efficacy and tolerability, clinical photography, bioinstrumentation, and a self-assessment questionnaire were performed at baseline and post-baseline. RESULTS: The TNT significantly improved horizontal neck fold lines and neck skin elasticity, hydration, gloss/radiance, and skin tone evenness post-baseline. Clinical photography and ultrasound corroborated these findings. The product was well perceived and well tolerated by subjects. CONCLUSION: This study demonstrated the TNT was effective against both extrinsic and intrinsic aging of the neck and jawline. The TNT provides a topical solution for Chinese women concerned with an aging appearance of the neck including "tech neck."

Antioxidant Skincare Treatment for Hyperpigmented and Photodamaged Skin: Multi-Center, Open-Label, Cross-Seasonal Case Study.

Objective: The objective of this study is three-fold. Firstly, to evaluate an enhanced vitamin C serum (eVCS) and its' combination with a retinol-bakuchiol serum (RBS) on pigmentation in vitro. Secondly, to evaluate the effect of the eVCS on skin function ex vivo. Lastly, to evaluate eVCS and RSB in the treatment of facial hyperpigmentation and overall photodamage across a range of opposing environments. Methods: MelanoDerm™ tissues were topically treated with the eVCS, and a eVCS and RSB blend for 14 days, and then a melanin assay was performed. Surgical waste facial skin explants were incubated with the eVCS or control for five days and then fixed and stained for skin physiology and structure. A 12-week, IRB approved, study on female subjects (n=29, aged 35 to 65) with moderate global facial hyperpigmentation and overall photodamage was completed. Clinical assessment, tolerability measurements, and subject-assessments were performed baseline at Weeks 6, 8, and 12. Investigator Global Aesthetic Improvement Score was completed at Week 12. Results: The eVCS-treated facial skin explants achieved a significant 145 percent collagen increase compared to control. The eVCS-RSB combination proved synergistic in reducing melanin compared to the eVCS alone. The eVCS-RSB combination demonstrated significant clinical improvement at all timepoints and was well tolerated. Subject responses were favorable and GAIS score of 3.0 was achieved at Week 12, indicating an improvement. Limitations: Limitations include lack of placebo or vehicle control. Conclusion: The product pairing, eVCS and RSB, offers patients an efficacious and well-tolerated treatment to target pigmentation and photodamage. Clinical Trial: This study, Pro00050557, was approved by Advarra IRB (Columbia, Maryland) and submitted to ClinicalTrials.gov #: NCT05423873.

Red blood cell-mimicking synthetic biomaterial particles.

Biomaterials form the basis of current and future biomedical technologies. They are routinely used to design therapeutic carriers, such as nanoparticles, for applications in drug delivery. Current strategies for synthesizing drug delivery carriers are based either on discovery of materials or development of fabrication methods. While synthetic carriers have brought upon numerous advances in drug delivery, they fail to match the sophistication exhibited by innate biological entities. In particular, red blood cells (RBCs), the most ubiquitous cell type in the human blood, constitute highly specialized entities with unique shape, size, mechanical flexibility, and material composition, all of which are optimized for extraordinary biological performance. Inspired by this natural example, we synthesized particles that mimic the key structural and functional features of RBCs. Similar to their natural counterparts, RBC-mimicking particles described here possess the ability to carry oxygen and flow through capillaries smaller than their own diameter. Further, they can also encapsulate drugs and imaging agents. These particles provide a paradigm for the design of drug delivery and imaging carriers, because they combine the functionality of natural RBCs with the broad applicability and versatility of synthetic drug delivery particles.

A case study investigating the short-term efficacy and tolerability of a daily serum composed from a unique sunflower sprout extract.

BACKGROUND: Fatigued skin, defined as dehydrated skin with lack of visual facial firmness and dull appearance, can be attributed to intrinsic and extrinsic factors of aging. An anti-aging daily serum (AADS) containing a unique sunflower sprout extract (SSE) was formulated to target fatigued and photodamaged skin. AIMS: Utilizing both preclinical and clinical testing models, the efficacy of the AADS was investigated to improve fatigued and photodamaged skin. PATIENTS/METHOD: Preclinical studies included in vitro analysis of adenosine triphosphate (ATP) production in fatigued dermal fibroblasts, inhibition of ultraviolet radiation A (UVA) induced advanced glycation end products (AGEs) in keratinocytes, and ex vivo gene expression after incubation with the SSE. An institutional review board (IRB)-approved short-term, 7-day, clinical case study was conducted on 28 female subjects, Fitzpatrick skin type I-IV, aged 30-60 years with moderate overall photodamage and skin fatigue. This was a double-blinded, randomized, controlled, single-center case study testing the AADS alone and in combination with an anti-aging facial moisturizer (AAFM). RESULTS: The SSE boosted intracellular ATP production in fatigued fibroblasts and reduced the formation of AGEs in keratinocytes. The SSE increased expression of genes related to epidermal keratinization and downregulated genes related to inflammation. Statistically significant improvement was found after 7 days of twice-daily use of the AADS alone and in combination with the AAFM. Products were well tolerated and perceived by subjects. CONCLUSION: Preclinical results combined with the clinical results strongly suggest that the AADS containing the SSE was tolerable and effective in targeting fatigued and photodamaged skin.

A Randomized, Double-blind, Placebo-controlled Clinical Study Investigating the Efficacy and Tolerability of a Peptide Serum Targeting Expression Lines.

Clinical Trial ID: NCT0454597 BACKGROUND: Mimetic wrinkles, commonly referred to as expression lines, form perpendicular to anatomical regions subjected to repeated facial muscle contraction. Neuromodulating peptides have biological activity and can offer a solution to those concerned with expression lines and facial aging. OBJECTIVE: The objective of this randomized, double-blind, placebo-controlled study was to assess the efficacy and tolerability of a line-targeting peptide serum (LTPS) as a stand-alone treatment in improving expression lines and skin health. METHODS: This was an institutional review board-approved study involving healthy subjects. Fifty-five female subjects, 35 to 60 years old, Fitzpatrick Skin Type I to VI, with mild to moderate global face fine lines and wrinkles were recruited. Subjects were randomized to apply LTPS or a placebo serum to their face twice daily for twelve weeks. Short-term efficacy was assessed after fifteen minutes of serum application at baseline. Long-term efficacy and tolerability, self-assessment questionnaire, and VISIA® clinical photography were performed at baseline, Weeks 4, 8, and 12. 3D PRIMOS CR imaging and wrinkle analysis were obtained at baseline and Weeks 8 and 12. RESULTS: The LTPS significantly improved expression lines at fifteen minutes (short term), Weeks 4, 8, and 12 (long term) when compared to the placebo serum as evaluated by a board-certified dermatologist. The LTPS significantly outperformed the placebo serum in improving skin parameters at all time points. VISIA and PRIMOS CR wrinkle analysis substantiated the LTPS's efficacy. LTPS was well-perceived and well tolerated by the subjects. CONCLUSION: This IRB-approved clinical study demonstrated that LTPS was effective in improving expression lines, wrinkles, and skin health after twelve weeks of application.

Effective lightening of facial melasma during the summer with a dual regimen: A prospective, open-label, evaluator-blinded study.

BACKGROUND: Melasma is a chronic pigmentary condition that can have significant negative effects on quality of life. Vitamin C can be effective in the treatment melasma, but its delivery often proves to be challenging due to instability of the drug and subsequent cutaneous irritation at higher concentrations. AIM: In this prospective, open-label, evaluator-blinded study, we aimed to assess the efficacy and tolerability of twice-daily application of a novel, highly potent, non-irritating 30% tetrahexyldecyl (THD) ascorbate serum in combination with 100% mineral-based sunscreen in the treatment of melasma during the summer months. PATIENTS/METHODS: Ten female subjects of ages ranging from 18 to 60 years underwent twice-daily application of 30% THD ascorbate serum in combination with an anti-aging 100% mineral tinted broad-spectrum protection SPF 45 sunscreen moisturizer for 12 weeks during the summer months (July to September). Two blinded evaluators scored baseline and post-treatment photographs using the Griffiths' 10-point scale and global aesthetic improvement scale. RESULTS: All subjects showed an improvement in hyperpigmentation with an average improvement of 33.7%. Seventy percent of subjects showed an improvement in skin tone evenness (redness), and among those subjects, the average improvement was 33.3%. The median global aesthetic improvement score was 2.0 (very much improved). CONCLUSION: Our study demonstrated efficacy and safety in treating the pigmentary as well as vascular components of melasma with a novel 30% THD ascorbate serum and a purely mineral-based tinted moisturizing sunscreen.

An open-label, single-site study to evaluate the tolerability, safety, and efficacy of using a novel facial moisturizer for preparation and accelerated healing pre and post a single full-face radiofrequency microneedling treatment.

BACKGROUND: Skincare cosmeceutical products have been shown to address intrinsic and extrinsic skin aging. Radiofrequency (RF) with microneedling is effective and safe in improving skin laxity and texture. Pairing skincare cosmeceutical products pre- and post-procedure is beneficial as it enhances patient results, patient results, patient experience, and reduces patient downtime. OBJECTIVE: To evaluate the tolerability, safety, and efficacy of a multi-ingredient anti-aging facial moisturizer when applied pre- and post-procedure consisting of a single RF microneedling treatment. METHOD: Fifteen female patients, aged 37-60, Fitzpatrick skin types I-IV, with mild-to-moderate wrinkles were included in the study. Patients applied a multi-ingredient anti-aging facial moisturizer twice a day (morning and night) two weeks prior to RF microneedling and four weeks post-RF microneedling (twice a day). At each time point, investigator objective assessment, self-assessments, and clinical photography were taken. RESULT: There were no adverse events as evaluated by the investigator. For this combined treatment and procedure patient scored comfort as the highest for satisfaction. Tolerability parameters erythema and edema were reported after RF microneedling treatment and were significant compared to the pre-procedure timepoint. Eighty percent of patients showed an improvement in Glogau Wrinkle Scale, but improvement was not statistically significant between baseline and end of study. Improvements in all skin attributes (radiance, tone, smoothness, texture, redness, dryness, and overall appearance) were statistically significant at the end of the study. Self-perceived skin attribute improvements included overall improvement, brightness, texture, pigmentation, redness, and tightness. The combination of the anti-aging facial moisturizer and RF microneedling was recommended by the patients in this study. CONCLUSION: This clinical study positively supports the hypothesis that combining the multi-ingredient anti-aging facial moisturizer pre- and post-RF microneedling was safe and tolerable for the patients.

Encapsulation of paclitaxel in macromolecular nanoshells.

An electrostatic layer-by-layer self-assembly technique was used to encapsulate solid core paclitaxel nanoparticles within a polymeric nanometer-scale shell. This approach provides a new strategy for the development of polymeric vehicles that control drug release and target diseased tissues and cells specific to the ailment, such as breast cancer. Core paclitaxel nanoparticles, 153 +/- 28 nm in diameter, were prepared using a modified nanoprecipitation technique. A nanoshell composed of multilayered polyelectrolytes, poly(allylamine hydrochloride) and poly(styrene-4-sulfonate) was assembled stepwise onto core charged drug nanoparticles. In vitro studies were performed to determine the anticancer activity of paclitaxel core-shell nanoparticles. Paclitaxel core-shell nanoparticles induced cell cycle arrest in the G2/M phase after 24 and 48 h of incubation with a human breast carcinoma cell line, MCF-7. Changes in MCF-7 cell morphology, fragmentation of the nucleus, and loss of cell-cell contacts indicated that the cells responded to paclitaxel core nanoparticles upon treatment for 24 and 48 h. Cells arrested in G2/M phase illustrated abnormal microtubule and actin cytoskeleton morphology. The core-shell drug nanoparticles fabricated using this procedure provide a new approach in the delivery of paclitaxel devoid of Cremophor EL, a solvent that causes adverse side effects in patients undergoing chemotherapy for treatment of metastasized mammary cancers.

Localized functionalization of individual colloidal carriers for cell targeting and imaging.

Fabricating drug particles for therapeutic delivery and imaging presents important challenges in the design of the particle surfaces. Drug nanoparticle surfaces are currently functionalized with site-specific targeting ligands, biocompatible polymers, or fluorophore-polymer conjugates for specific imaging. However, if these functionalizations were to be synthesized on the drug carrier in localized, nanoscale regions on the particle surface, new schemes of drug delivery could be realized. Here we describe the use of our particle lithography technique that enables the synthesis of individual colloidal carrier assemblies that can be imaged and targeted to integrin-expressing cells. We show localized adhesion specificity for cells expressing the target integrin followed by receptor-mediated endocytosis. With the addition of localized delivery by adding drug nanoparticles to a specific region on the particle surface, our colloidal carrier assemblies have the potential to target, deliver therapeutic agents to, sense, and image diseased endothelium.

Cell adhesion on nanofibrous polytetrafluoroethylene (nPTFE).

Here, we described the in vitro biocompatibility of a novel nanostructured surface composed of PTFE as a potential polymer for the prevention of adverse host reactions to implanted devices. The foreign body response is characterized at the tissue-material interface by several layers of macrophages and large multinucleated cells known as foreign body giant cells (FBGC), and a fibrous capsule. The nanofibers of nanofibrous PTFE (nPTFE) range in size from 20 to 30 nm in width and 3-4 mm in length. Glass surfaces coated with nPTFE (produced by jet-blowing of PTFE 601A) were tested under in vitro conditions to characterize the amount of protein adsorption, cell adhesion, and cell viability. We have shown that nPTFE adsorbs 495 +/- 100 ng of bovine serum albumin (BSA) per cm2. This level was considerably higher than planar PTFE, most likely due to the increase in hydrophobicity and available surface area, both a result of the nanoarchitecture. Endothelial cells and macrophages were used to determine the degree of cell adsorption on the surface of the nanostructured polymer. Both cell types were significantly more round and occupied less area on nPTFE as compared to tissue culture polystyrene (TCPS). Furthermore, a larger majority of the cells on the nPTFE were dead compared to TCPS, at dead-to-live ratios of 778 +/- 271 to 1 and 23 +/- 5.6 to 1, respectively. Since there was a high amount of cell death (due to either apoptosis or necrosis), and the foreign body response is a form of chronic inflammation, an 18 cytokine Luminex panel was performed on the supernatant from macrophages adherent on nPTFE and TCPS. As a positive control for inflammation, lipopolysaccharide (LPS) was added to macrophages on TCPS to estimate the maximum inflammation response of the macrophages. From the data presented with respect to IL-1, TNF-alpha, IFN-gamma, and IL-5, we concluded that nPTFE is nonimmunogenic and should not yield a huge inflammatory response in vivo, and cell death observed on the surface of nPTFE was likely due to apoptosis resulting from the inability of cells to spread on these surface. On the basis of the production of IL-1, IL-6, IL-4, and GM-CSF, we concluded that FBGC formation on nPTFE may be decreased as compared to materials known to elicit FBGC formation in vivo.

Macrophage uptake of core-shell nanoparticles surface modified with poly(ethylene glycol).

The in vitro uptake of core-shell nanoparticles encapsulated in a bio-macromolecular nanoshell assembled from multilayered polyelectrolytes was studied. Sulfate modified fluorescent polystyrene nanobeads (diameter 200 nm) were used as a solid core upon which charged multilayers of poly-l-lysine, chitosan, and heparin sulfate are electrostatically deposited utilizing a layer-by-layer (LbL) self-assembly process. The nanoshell composed of the multilayered polyelectrolytes was modified with poly(ethylene glycol) (PEG) of varying molecular weights (either MW 2000, 5000, or 20 000 Da) to form a hydrophilic and long-circulating nanoparticle. The assembly of the nanoshell was confirmed by zeta potential, transmission electron microscopy (TEM), and X-ray photoelectron spectroscopy (XPS). The reversal in charge upon the deposition of alternating polyelectrolytes was observed by zeta potential measurements. The nanometer thickness of the nanoshell was confirmed by TEM. The presence of the (C-C-O)(n)() backbone in PEG at the surface of the nanoshell was confirmed by the increase in (C-O,N) peak area concentrations compared to (C-C) peak area, and these results were gathered from XPS. In vitro studies between suspension macrophages and core-shell nanoparticles were performed to determine how the hydrophilicity and the charge on the nanoshell can promote or reduce uptake. Results showed that after 24 h uptake was decreased 3-fold when PEGs of 2000 and 20 000 Da were chemisorbed to the nanoshell, as opposed to a nanoshell with either a positive or highly negative charge. Confocal microscopy aided in verifying that core-shell nanoparticles were internalized within the cell cytoplasm and were not attached to the cell surface. Protein adhesion studies with bovine serum albumin were performed to determine the relationship between surface charge and opsonization of core-shell nanoparticles. It was found that a hydrophilic surface with a low negative charge reduced protein adsorption and uptake. The in vitro uptake of macrophages and protein adsorption onto core-shell nanoparticles formed using layer-by-layer assembly has not been previously studied.

Encapsulation of drug nanoparticles in self-assembled macromolecular nanoshells.

Layer-by-Layer (LbL) stepwise self-assembly of the polyelectrolytes poly(allylamine hydrochloride) and poly(styrenesulfonate) was used to create a macromolecular nanoshell around drug nanoparticles (approximately 150 nm in diameter). Dexamethasone, a steroid often used in conjugation with chemotherapy, was chosen as a model drug and was formulated into nanoparticles using a modified solvent-evaporation emulsification method. Measurement of the zeta potential (zeta-potential) after each polyelectrolyte layer was electrostatically added confirmed the successful addition of each layer. Additionally, data acquired from X-ray photon spectroscopy (XPS) indicated the presence of peaks representative of each physisorbed polyelectrolyte layer. Surface modification of the nanoshell was performed by covalently attaching poly(ethylene glycol) (PEG) with a molecular weight of 2000 to the outer surface of the nanoshell. Zeta potential measurements and XPS indicated the presence of PEG chains at the surface of the nanoshell. The polymeric nanoshell on the surface of the drug nanoparticle provides a template upon which surface modifications can be made to create a stealth or targeted drug delivery system.